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1. Lau Q, Scheithauer B, Kovacs K, Horvath E, Syro LV, Lloyd R: MGMT immunoexpression in aggressive pituitary adenoma and carcinoma. Pituitary; 2010 Dec;13(4):367-79
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] MGMT immunoexpression in aggressive pituitary adenoma and carcinoma.
  • Recent case reports have documented the efficacy of temozolomide therapy in some aggressive pituitary adenomas and pituitary carcinomas resistant to multimodality therapy.
  • Herein, we aimed to study MGMT immunoexpression in a spectrum of pituitary tumors, indolent, aggressive and malignant.
  • A literature review of the use of temozolomide in pituitary tumors was also performed.
  • Immunohistochemistry for MGMT was performed on 60 pituitary tumors identified in the Mayo Clinic Tissue Registry and the consultation files of one of us (BWS).
  • The group included 30 pituitary carcinomas (15 ACTH, 10 PRL, 1 FSH/LH, 1 TSH, 1 silent subtype 3 and 2 null cell).
  • In addition, 30 functionally different pituitary adenomas were studied, including 15 invasive and 15 non-invasive adenomas.
  • Overall, 32 cases of pituitary tumors (54%) demonstrated low MGMT immunoexpression.
  • This included 17 of 30 (57%) carcinomas, 9 of 15 (60%) invasive adenomas, and 6 of 15 cases (40%) of non-invasive pituitary adenomas.
  • Prolactin-producing carcinomas had the highest proportion of tumors (80%) with low expression.
  • A significant proportion of pituitary adenomas and carcinomas demonstrate low MGMT immunoexpression.
  • In an effort to anticipate the likelihood of a temozolomide response, all cases of aggressive pituitary tumors should be assessed for MGMT expression.
  • [MeSH-major] DNA Modification Methylases / metabolism. DNA Repair Enzymes / metabolism. Pituitary Neoplasms / immunology. Tumor Suppressor Proteins / metabolism

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  • (PMID = 20740317.001).
  • [ISSN] 1573-7403
  • [Journal-full-title] Pituitary
  • [ISO-abbreviation] Pituitary
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 0 / Tumor Suppressor Proteins; 7GR28W0FJI / Dacarbazine; EC 2.1.1.- / DNA Modification Methylases; EC 2.1.1.63 / MGMT protein, human; EC 6.5.1.- / DNA Repair Enzymes; YF1K15M17Y / temozolomide
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2. Witek P, Zgliczyński W, Zieliński G, Jeske W: The role of combined low-dose dexamethasone suppression test and desmopressin stimulation test in the diagnosis of persistent Cushing's disease. Case report. Endokrynol Pol; 2010 May-Jun;61(3):312-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The role of combined low-dose dexamethasone suppression test and desmopressin stimulation test in the diagnosis of persistent Cushing's disease. Case report.
  • Cushing's disease is related to a significant increase in mortality due to chronic hypercortisolaemia complications.
  • The authors discuss the case of a patient, currently aged 60, after repeat pituitary surgery, with progressive cardiovascular complications, in whom persistent Cushing's disease was diagnosed.
  • The diagnosis was determined despite normal plasma ACTH, serum cortisol levels, and 17-OHCS concentrations in daily urine.
  • There was also a lack of obvious pituitary adenoma features in the magnetic resonance imaging (MRI).
  • Persistent Cushing's disease was diagnosed based on the combined dexamethasone desmopressin test.
  • The presented case points to the role of provocative testing, including the desmopressin test following 1 mg of dexamethasone, for diagnostically difficult cases of Cushing's disease.
  • [MeSH-major] Deamino Arginine Vasopressin. Dexamethasone. Pituitary ACTH Hypersecretion / diagnosis
  • [MeSH-minor] Early Diagnosis. Female. Humans. Middle Aged

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  • (PMID = 20602307.001).
  • [ISSN] 0423-104X
  • [Journal-full-title] Endokrynologia Polska
  • [ISO-abbreviation] Endokrynol Pol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Poland
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; ENR1LLB0FP / Deamino Arginine Vasopressin
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3. Castinetti F, Brue T: Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat? Discov Med; 2010 Aug;10(51):107-11
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  • [Title] Gamma Knife radiosurgery in pituitary adenomas: Why, who, and how to treat?
  • Pituitary adenomas are benign tumors that can be either secreting (acromegaly, Cushing's disease, prolactinomas) or non-secreting.
  • Several studies reported the efficacy and low risk of adverse effects induced by this technique: in secreting pituitary adenomas, hypersecretion is controlled in about 50% of cases and tumor volume is stabilized or decreased in 80-90% of cases, making Gamma Knife a valuable adjunctive or first-line treatment.
  • As hormone levels decrease progressively, the main drawback is the longer time to remission (12-60 months), requiring an additional treatment during this period.
  • Gamma Knife is thus useful in the therapeutic algorithms of pituitary adenomas in well-defined indications, mainly low secreting small lesions well identified on magnetic resonance imaging (MRI).
  • [MeSH-major] Pituitary Neoplasms / surgery. Radiosurgery / methods

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  • (PMID = 20807470.001).
  • [ISSN] 1944-7930
  • [Journal-full-title] Discovery medicine
  • [ISO-abbreviation] Discov Med
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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4. Lamberts SW, Hofland LJ: Future treatment strategies of aggressive pituitary tumors. Pituitary; 2009;12(3):261-4
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Future treatment strategies of aggressive pituitary tumors.
  • While surgery remains the first-line treatment of most aggressive pituitary adenomas, medical therapy is important as second-line or adjunctive therapy in a large proportion of patients.
  • There is an urgent need for medical therapies in Cushing's disease, and the SSTR(5) analogs could offer an effective treatment in a proportion of patients within the next few years.
  • Finally, the medical management options for non-functioning pituitary adenomas are also very limited, and a new chimeric agent with activity towards dopamine receptors, SSTR(5) and SSTR(2) may help reduce adenoma recurrence in the future.
  • [MeSH-major] Dopamine Agonists / therapeutic use. Pituitary Neoplasms
  • [MeSH-minor] Acromegaly / drug therapy. Humans. Octreotide / therapeutic use. Peptides, Cyclic / therapeutic use. Pituitary ACTH Hypersecretion / drug therapy. Pituitary ACTH Hypersecretion / surgery. Prolactinoma / drug therapy. Prolactinoma / surgery. Receptors, Somatostatin / antagonists & inhibitors. Somatostatin / analogs & derivatives. Somatostatin / therapeutic use

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  • [ISSN] 1573-7403
  • [Journal-full-title] Pituitary
  • [ISO-abbreviation] Pituitary
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
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  • [Other-IDs] NLM/ PMC2712619
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5. Nemergut EC, Dumont AS, Barry UT, Laws ER: Perioperative management of patients undergoing transsphenoidal pituitary surgery. Anesth Analg; 2005 Oct;101(4):1170-81
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Perioperative management of patients undergoing transsphenoidal pituitary surgery.
  • Pituitary adenomas often present with the symptoms of hormonal hypersecretion, and although medical therapy is available for most hyperfunctioning states, it is not curative.
  • As a result, transsphenoidal pituitary surgery has become a commonly performed neurosurgical procedure with unique challenges for the anesthesiologist due to the distinct medical comorbidities associated with various adenomas.
  • Any type of pituitary tumor may also produce hypopituitarism and local mass effects secondary to the expanding intrasellar mass.
  • Special attention is given to Cushing's disease (hypercortisolism secondary to an adrenocorticotropic hormone-secreting adenoma), acromegaly (secondary to a growth hormone-secreting adenoma), and hyperthyroidism in the setting of thyrotropic adenomas.
  • Operative risks, including bleeding, diabetes insipidus, the syndrome of inappropriate antidiuretic hormone secretion, and hypopituitarism, are addressed in detail.
  • [MeSH-major] Adenoma / surgery. Perioperative Care. Pituitary Neoplasms / surgery

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  • [CommentIn] Anesth Analg. 2007 Sep;105(3):886 [17717270.001]
  • (PMID = 16192540.001).
  • [ISSN] 0003-2999
  • [Journal-full-title] Anesthesia and analgesia
  • [ISO-abbreviation] Anesth. Analg.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] United States
  • [Number-of-references] 99
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6. Hellman P, Linder F, Hennings J, Hessman O, Eriksson B, Orlefors H, Akerström G: Bilateral adrenalectomy for ectopic Cushing's syndrome-discussions on technique and indication. World J Surg; 2006 May;30(5):909-16
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  • [Title] Bilateral adrenalectomy for ectopic Cushing's syndrome-discussions on technique and indication.
  • BACKGROUND: Tumors producing adrenocorticotropic hormone (ACTH) or corticotropin releasing hormone (CRH) often remain undiagnosed until severe Cushing's syndrome appears, and it may be difficult to distinguish from Cushing's syndrome due to pituitary tumors.
  • Many patients suffer from disease spread, with metastases in the liver or other locations, and the main symptoms may be mineral disturbances, diabetes mellitus, or psychological symptoms from the severe hypercortisolism.
  • METHODS: We have retrospectively investigated 8 patients with ectopic Cushing's syndrome who have undergone bilateral adrenalectomy at the University Hospital in Uppsala.
  • In addition, another 5 patients who underwent bilateral adrenalectomy for other reasons (recurrent pituitary Mb Cushing or bilateral hyperplasia) were scrutinized for technical considerations.
  • RESULTS: Curative surgery was not possible in any of the cases with ectopic Cushing's syndrome.
  • Moreover, bilateral adrenalectomy can substantially reduce the symptoms of Cushing's syndrome, although effects on mortality are not obvious.
  • [MeSH-major] Adrenalectomy / methods. Cushing Syndrome / surgery

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7. Keil MF, Stratakis CA: Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics. Expert Rev Neurother; 2008 Apr;8(4):563-74
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  • [Title] Pituitary tumors in childhood: update of diagnosis, treatment and molecular genetics.
  • Pituitary tumors are rare in childhood and adolescence, with a reported prevalence of up to one per 1 million children.
  • Only 2-6% of surgically treated pituitary tumors occur in children.
  • Although pituitary tumors in children are almost never malignant and hormonal secretion is rare, these tumors may result in significant morbidity.
  • Tumors within the pituitary fossa are mainly of two types: craniopharyngiomas and adenomas.
  • Craniopharyngiomas cause symptoms by compressing normal pituitary, causing hormonal deficiencies and producing mass effects on surrounding tissues and the brain; adenomas produce a variety of hormonal conditions such as hyperprolactinemia, Cushing disease and acromegaly or gigantism.
  • Little is known about the genetic causes of sporadic lesions, which comprise the majority of pituitary tumors, but in children, more frequently than in adults, pituitary tumors may be a manifestation of genetic conditions such as multiple endocrine neoplasia type 1, Carney complex, familial isolated pituitary adenoma and McCune-Albright syndrome.
  • The study of pituitary tumorigenesis in the context of these genetic syndromes has advanced our knowledge of the molecular basis of pituitary tumors and may lead to new therapeutic developments.

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  • (PMID = 18416659.001).
  • [ISSN] 1744-8360
  • [Journal-full-title] Expert review of neurotherapeutics
  • [ISO-abbreviation] Expert Rev Neurother
  • [Language] ENG
  • [Grant] United States / NICHD NIH HHS / HD / Z01 HD000642; United States / Intramural NIH HHS / / Z01 HD000642-10
  • [Publication-type] Journal Article; Research Support, N.I.H., Intramural; Review
  • [Publication-country] England
  • [Number-of-references] 123
  • [Other-IDs] NLM/ NIHMS102071; NLM/ PMC2743125
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8. Gemmill JA, Stratton P, Cleary SD, Ballweg ML, Sinaii N: Cancers, infections, and endocrine diseases in women with endometriosis. Fertil Steril; 2010 Oct;94(5):1627-31
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  • [Title] Cancers, infections, and endocrine diseases in women with endometriosis.
  • MAIN OUTCOME MEASURE(S): Self-reported, physician-diagnosed infectious diseases, cancers, and endocrine diseases.
  • Addison's disease and Cushing's syndrome were rare (0.2% and 0.1%, respectively).
  • These findings document other potential associations related to the immune system, which may help focus future research into this disease.
  • [MeSH-major] Endocrine System Diseases / epidemiology. Endometriosis / epidemiology. Melanoma / epidemiology. Ovarian Neoplasms / epidemiology. Respiratory Tract Infections / epidemiology. Uterine Diseases / epidemiology. Vaginal Diseases / epidemiology
  • [MeSH-minor] Addison Disease / epidemiology. Adolescent. Adult. Aged. Comorbidity. Congenital Abnormalities / epidemiology. Cross-Sectional Studies. Cushing Syndrome / epidemiology. Female. Humans. Middle Aged. Mitral Valve Prolapse / epidemiology. Prevalence. Recurrence. Self Disclosure. Skin Neoplasms / epidemiology. Young Adult


9. McFarlane D, Beech J, Cribb A: Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants. Domest Anim Endocrinol; 2006 May;30(4):276-88
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  • [Title] Alpha-melanocyte stimulating hormone release in response to thyrotropin releasing hormone in healthy horses, horses with pituitary pars intermedia dysfunction and equine pars intermedia explants.
  • Thyrotropin releasing hormone (TRH) stimulates an increase in plasma cortisol in horses with pars intermedia dysfunction (PPID, Cushing's disease).
  • A similar phenomenon is observed in humans with Cushing's disease or Nelson's syndrome.
  • Using alpha-melanocyte stimulating hormone (alpha-MSH) as a marker of a PI response and ACTH as a marker of a PD response, we were able to demonstrate a marked increase in plasma concentration of alpha-MSH and a modest, but significant increase in ACTH after TRH treatment in normal horses.
  • The increase in plasma cortisol following TRH in horses with PPID is likely attributable to the release of ACTH from the hyperplastic PI.
  • [MeSH-major] Horse Diseases / physiopathology. Pituitary Diseases / veterinary. Pituitary Gland / secretion. Thyrotropin-Releasing Hormone / pharmacology. alpha-MSH / secretion
  • [MeSH-minor] Adrenocorticotropic Hormone / blood. Adrenocorticotropic Hormone / secretion. Animals. Base Sequence. Cushing Syndrome / physiopathology. Cushing Syndrome / veterinary. Female. Horses. Hydrocortisone / blood. Male. Molecular Sequence Data. Organ Culture Techniques. RNA, Messenger / analysis. Receptors, Thyrotropin-Releasing Hormone / genetics. Reverse Transcriptase Polymerase Chain Reaction. Sequence Homology

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  • (PMID = 16115743.001).
  • [ISSN] 0739-7240
  • [Journal-full-title] Domestic animal endocrinology
  • [ISO-abbreviation] Domest. Anim. Endocrinol.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / RNA, Messenger; 0 / Receptors, Thyrotropin-Releasing Hormone; 581-05-5 / alpha-MSH; 5Y5F15120W / Thyrotropin-Releasing Hormone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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10. Markou A, Manning P, Kaya B, Datta SN, Bomanji JB, Conway GS: [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing's syndrome. Eur J Endocrinol; 2005 Apr;152(4):521-5
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  • [Title] [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography imaging of thymic carcinoid tumor presenting with recurrent Cushing's syndrome.
  • We report a case of a young woman with Cushing's syndrome (CS), in whom although endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion, the results of inferior petrosal sinus (IPS) sampling after coricotropin-releasing hormone (CRH) stimulation were suggestive of pituitary ACTH hypersecretion. (111)In-labelled octreotide and high-resolution computer tomography (CT) revealed a lesion possibly responsible for the ACTH source in the thymus.
  • Thymectomy confirmed concomitant ectopic CRH and probable ACTH production by a thymic neuroendocrine carcinoma.
  • A repeat [(18)F]FDG PET study showed persistent disease in the thymic bed and also uptake in the adrenals.
  • This is a rare case of concomitant CRH and ACTH secretion from a thymic carcinoid tumor; the case illustrates the usefulness of functional imaging with [(18)F]FDG PET in the diagnosis, management and follow-up of neuroendocrine tumors.


11. Schmid HA, Silva AP: Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH, corticosterone and ghrelin in rats. J Endocrinol Invest; 2005;28(11 Suppl International):28-35
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  • [Title] Short- and long-term effects of octreotide and SOM230 on GH, IGF-I, ACTH, corticosterone and ghrelin in rats.
  • In the pituitary of patients with primary Cushing's disease, the SSTR5 is more frequently expressed than SSTR2.
  • Accordingly, in rats SOM230 caused a stronger inhibition of ACTH and corticosterone secretion than octreotide.
  • [MeSH-major] Adrenocorticotropic Hormone / secretion. Growth Hormone / secretion. Insulin-Like Growth Factor I / secretion. Octreotide / pharmacology. Peptide Hormones / secretion. Somatostatin / analogs & derivatives
  • [MeSH-minor] Animals. Corticosterone / secretion. Corticotropin-Releasing Hormone / pharmacology. Ghrelin. Male. Rats. Rats, Sprague-Dawley. Receptors, Somatotropin / drug effects. Receptors, Somatotropin / metabolism. Thyrotropin / secretion. Thyrotropin-Releasing Hormone / pharmacology

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  • (PMID = 16625842.001).
  • [ISSN] 0391-4097
  • [Journal-full-title] Journal of endocrinological investigation
  • [ISO-abbreviation] J. Endocrinol. Invest.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Ghrelin; 0 / Peptide Hormones; 0 / Receptors, Somatotropin; 51110-01-1 / Somatostatin; 5Y5F15120W / Thyrotropin-Releasing Hormone; 67763-96-6 / Insulin-Like Growth Factor I; 9002-60-2 / Adrenocorticotropic Hormone; 9002-71-5 / Thyrotropin; 9002-72-6 / Growth Hormone; 9015-71-8 / Corticotropin-Releasing Hormone; 98H1T17066 / pasireotide; RWM8CCW8GP / Octreotide; W980KJ009P / Corticosterone
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12. Scommegna S, Greening JP, Storr HL, Davies KM, Shaw NJ, Monson JP, Grossman AB, Savage MO: Bone mineral density at diagnosis and following successful treatment of pediatric Cushing's disease. J Endocrinol Invest; 2005 Mar;28(3):231-5
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  • [Title] Bone mineral density at diagnosis and following successful treatment of pediatric Cushing's disease.
  • Bone mineral density (BMD) is frequently reduced in children and adolescents with Cushing's disease (CD), but there is little follow-up data after cure.
  • Group 1 comprised 8 patients, 5 males and 3 females, aged 12.4 yr (8.2-16.8), assessed at diagnosis.
  • =7) or TSS + pituitary irradiation (no.=4).
  • L2-L4 vBMD Z-score values correlated negatively with midnight cortisol (p < 0.05).
  • These findings show variability of BMD at diagnosis and near normal BMD after cure of pediatric CD, suggesting that with appropriate replacement of pituitary hormone deficiency normal peak bone mass is achievable.
  • [MeSH-major] Bone Density / physiology. Cushing Syndrome / pathology
  • [MeSH-minor] Absorptiometry, Photon. Adolescent. Child. Cross-Sectional Studies. Disease Progression. Endocrine Glands / physiopathology. Female. Follow-Up Studies. Hormones / blood. Human Growth Hormone / deficiency. Humans. Hydrocortisone / blood. Male. Pituitary Gland / surgery

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  • (PMID = 15952407.001).
  • [ISSN] 0391-4097
  • [Journal-full-title] Journal of endocrinological investigation
  • [ISO-abbreviation] J. Endocrinol. Invest.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / Hormones; 12629-01-5 / Human Growth Hormone; WI4X0X7BPJ / Hydrocortisone
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13. Bertagna X, Guignat L, Groussin L, Bertherat J: Cushing's disease. Best Pract Res Clin Endocrinol Metab; 2009 Oct;23(5):607-23
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  • [Title] Cushing's disease.
  • Cushing's syndrome refers to the clinical manifestations induced by chronic exposure to excess glucocorticoids.
  • There are three pathological conditions that can result in the chronic overproduction of endogenous cortisol in man: the most frequent is Cushing's disease where adrenocorticotropic hormone (ACTH) is overproduced by a pituitary corticotroph adenoma, rarely ACTH can be produced in an 'ectopic' manner by a non-pituitary tumour, finally cortisol can be directly over-secreted by one or (rarely) the two adrenals that have become tumourous, either benign or malignant.
  • The positive diagnosis of Cushing's syndrome requires that chronic hypercortisolism is unequivocally demonstrated biologically, using 24-h urinary cortisol, late-evening plasma or salivary cortisol, midnight 1-mg or the classic 48-h-low-dose dexamethasone suppression test, etc., all with essentially the same diagnosis potencies.
  • The search for the responsible tumour then relies on the assessment of the corticotroph function, and imaging: suppressed ACTH plasma levels indicate an 'adrenal' Cushing, and the responsible unilateral adrenocortical tumour is always visible at computed tomography (CT) scan, whereas its benign or malignant nature may be difficult to diagnose before surgery.
  • Imaging can suspect bilateral 'adrenal' Cushing, when the two adrenals are small, as in the primary pigmented nodular adrenal dysplasia associated with Carney complex, or enlarged, as in the ACTH-independent macronodular adrenocortical hyperplasia.
  • Measurable or increased ACTH plasma levels indicate either Cushing's disease or the ectopic ACTH syndrome.
  • This is the situation where sampling ACTH plasma levels in the inferior petrosal sinus may be necessary.
  • The best treatment option of Cushing's disease is when the responsible corticotroph adenoma can be entirely removed by the trans-sphenoidal approach, with sufficient skill to preserve the normal anterior pituitary function.
  • When it fails, all other options directed towards the pituitary (radiation therapies), or the adrenals (medications or surgery), have numerous side effects.
  • There is at present no recognised efficient medical treatment towards the corticotroph adenoma -still an orphan disease.
  • [MeSH-major] Pituitary ACTH Hypersecretion / etiology
  • [MeSH-minor] Algorithms. Cushing Syndrome / diagnosis. Cushing Syndrome / etiology. Diagnosis, Differential. Diagnostic Errors. Diagnostic Techniques, Endocrine. Humans. Prognosis

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  • (PMID = 19945026.001).
  • [ISSN] 1878-1594
  • [Journal-full-title] Best practice & research. Clinical endocrinology & metabolism
  • [ISO-abbreviation] Best Pract. Res. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Netherlands
  • [Number-of-references] 74
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14. Nao S, Adachi Y, Sato S: [Anesthesia for a patient with Cushing's disease and hepatitis B]. Masui; 2008 Jun;57(6):745-7
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  • [Title] [Anesthesia for a patient with Cushing's disease and hepatitis B].
  • She showed a complication of Cushing's disease and hepatitis was initially treated with lamivudine administration as well as inhibition and supplementation of cortisol, because hypercortisolemia could induce massive liver necrosis with hepatitis.
  • After inducing remission phase, Hardy's operation for pituitary microadenoma was scheduled.
  • [MeSH-major] Anesthesia, Inhalation / methods. Cushing Syndrome / complications. Hepatitis B, Chronic / complications
  • [MeSH-minor] Adult. Female. Humans. Pituitary Neoplasms / surgery

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  • (PMID = 18546907.001).
  • [ISSN] 0021-4892
  • [Journal-full-title] Masui. The Japanese journal of anesthesiology
  • [ISO-abbreviation] Masui
  • [Language] jpn
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] Japan
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15. Castinetti F, Morange I, Jaquet P, Conte-Devolx B, Brue T: Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease. Eur J Endocrinol; 2008 Jan;158(1):91-9
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  • [Title] Ketoconazole revisited: a preoperative or postoperative treatment in Cushing's disease.
  • CONTEXT: Although transsphenoidal surgery remains the first-line treatment in Cushing's disease (CD), recurrence is observed in about 20% of cases.
  • MAIN OUTCOME MEASURES: Patients were considered controlled if 24-h urinary free cortisol was normalized.
  • Among 15 patients without visible adenoma at initial evaluation, subsequent follow-up allowed identification of the lesion in five cases.
  • CONCLUSIONS: Ketoconazole is a safe and efficacious treatment in CD, particularly in patients for whom surgery is contraindicated, or delayed because of the absence of image of adenoma on magnetic resonance imaging.


16. Pawlikowski M, Kunert-Radek J, Radek M: "Silent"corticotropinoma. Neuro Endocrinol Lett; 2008 Jun;29(3):347-50
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  • OBJECTIVES: The aim of the study was to evaluate the ACTH-immunopositive pituitary adenomas, especially those without manifestation of Cushing's disease MATERIAL AND METHODS: 148 pituitary adenomas removed surgically in years 1994--2007 were studied.
  • The paraffin sections were immunostained with antibodies against the pituitary hormones.
  • In 79 adenomas the immunostaining with anti-ACTH antibody was performed Additionally, 23 tumors were also immunostained with anti-Ki-67 (MIB-1) antibody.
  • RESULTS: ACTH immunopositivity was found in 34 cases (23%).
  • Fourteen ACTH-immunopositive tumors manifested themselves as Cushing's disease (including 1 case of Nelson's syndrome).
  • In the remaining 20 cases in spite of the positive immunostaining for ACTH of the tumor cells, no features of hypercortisolism were observed (in several cases even hypocortisolism was found).
  • Over one third (37%) of "clinically" nonfunctioning pituitary adenomas, when immunostained with anti-ACTH antibody, showed ACTH immunopositivity.
  • Three adenomas in patients with Cushing's disease (21.4%) and 7 "silent" corticotropinomas (35%) were recurrent tumors.
  • In contrast, the recurrence rate in the group of ACTH-immunonegative clinically nonfunctioning pituitary adenomas was 14.7%.
  • The "silent" corticotropinomas exhibited a tendency towards the higher expression of a proliferation marker, Ki-67 antigen as compared to the "active" corticotropinomas.
  • CONCLUSIONS: (i) "Silent" corticotropinomas are rather frequent. (ii) This adenoma type should be considered as aggressive. (iii) It is hypothetized that--like in Nelson's syndrome--the lack of hypercortisolism or even presence of hypocortisolism favorizes the exaggerated growth of tumoral corticotrophs.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / metabolism. Adenoma / metabolism. Adrenocorticotropic Hormone / metabolism
  • [MeSH-minor] Adult. Cushing Syndrome / blood. Cushing Syndrome / pathology. Female. Humans. Immunohistochemistry. Ki-67 Antigen / blood. Male. Nelson Syndrome / blood. Paraffin Embedding. Pituitary Hormones / metabolism

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  • (PMID = 18580839.001).
  • [ISSN] 0172-780X
  • [Journal-full-title] Neuro endocrinology letters
  • [ISO-abbreviation] Neuro Endocrinol. Lett.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Sweden
  • [Chemical-registry-number] 0 / Ki-67 Antigen; 0 / Pituitary Hormones; 9002-60-2 / Adrenocorticotropic Hormone
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17. Hayashi N, Kurimoto M, Kubo M, Kuwayama N, Kurosaki K, Nagai S, Endo S: The impact of cavernous sinus drainage pattern on the results of venous sampling in patients with suspected cushing syndrome. AJNR Am J Neuroradiol; 2008 Jan;29(1):69-72
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  • [Title] The impact of cavernous sinus drainage pattern on the results of venous sampling in patients with suspected cushing syndrome.
  • BACKGROUND AND PURPOSE: Selective venous sampling from the posterior portion of the cavernous sinus (CS) is recommended for the diagnosis of Cushing disease, because samples from the posterior portion yield higher adrenocorticotropic hormone (ACTH) levels than those from the anterior and middle portions.
  • We prospectively assessed this intracavernous gradient of ACTH level to determine which site in the CS yields adequate sampling.
  • MATERIALS AND METHODS: In 5 patients with Cushing syndrome, cavernous sinography was performed to assess drainage pattern of the CS.
  • In 1 patient with an ectopic lesion, no increase in ACTH level was detected.
  • In 3 of 4 patients with Cushing disease, the highest C/P ratio was obtained from the posterior portion.
  • [MeSH-major] Adrenocorticotropic Hormone / blood. Blood Specimen Collection / methods. Cavernous Sinus / metabolism. Cushing Syndrome / blood. Cushing Syndrome / diagnosis

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  • (PMID = 17925372.001).
  • [ISSN] 1936-959X
  • [Journal-full-title] AJNR. American journal of neuroradiology
  • [ISO-abbreviation] AJNR Am J Neuroradiol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
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18. Georgiadis AN, Papavasiliou EC, Lourida ES, Alamanos Y, Kostara C, Tselepis AD, Drosos AA: Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment--a prospective, controlled study. Arthritis Res Ther; 2006;8(3):R82
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  • These patients had disease durations of less than one year and had not had prior treatment for it.
  • Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study.
  • Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients.
  • The mean DAS-28 at disease onset was 5.8 +/- 0.9.
  • Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.


19. Gierach M, Pufal J, Pilecki S, Junik R: The case of Cushing's disease imaging by SPECT examination without manifestation of pituitary adenoma in MRI examination. Nucl Med Rev Cent East Eur; 2005;8(2):137-9
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  • [Title] The case of Cushing's disease imaging by SPECT examination without manifestation of pituitary adenoma in MRI examination.
  • BACKGROUND: The aim of our study was to evaluate the possibility of imaging the pathological accumulation of (99m)Tc-MIBI in the pituitary gland in patients with Cushing's disease when MRI examination does not show microadenomas.
  • MATERIAL AND METHODS: Cushing's disease was diagnosed in a 27 year old male on the basis of clinical and biochemical findings.
  • The blood cortisol level of the patient was elevated (the average level was 47 ug/dl) and it showed no changeability of day and night rhythm.
  • RESULTS: In the patient with Cushing's disease, during the SPECT examination, an increased accumulation of (99m)Tc-MIBI in the pituitary gland was noticed.
  • CONCLUSION: Single photon emission computed tomography using (99m)Tc-MIBI is a useful and sensitive means of pituitary gland microadenoma detection in patients with Cushing's disease when microadenoma is not detected during MRI scanning and when the results of dexamethasone suppression test is positive.
  • [MeSH-major] Adenoma / diagnosis. Cushing Syndrome / diagnosis. Magnetic Resonance Imaging. Pituitary Neoplasms / diagnosis. Technetium Tc 99m Sestamibi. Tomography, Emission-Computed, Single-Photon

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  • (PMID = 16437402.001).
  • [ISSN] 1506-9680
  • [Journal-full-title] Nuclear medicine review. Central & Eastern Europe
  • [ISO-abbreviation] Nucl Med Rev Cent East Eur
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Poland
  • [Chemical-registry-number] 0 / Radiopharmaceuticals; 971Z4W1S09 / Technetium Tc 99m Sestamibi
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20. Friedman TC, Zuckerbraun E, Lee ML, Kabil MS, Shahinian H: Dynamic pituitary MRI has high sensitivity and specificity for the diagnosis of mild Cushing's syndrome and should be part of the initial workup. Horm Metab Res; 2007 Jun;39(6):451-6
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  • [Title] Dynamic pituitary MRI has high sensitivity and specificity for the diagnosis of mild Cushing's syndrome and should be part of the initial workup.
  • AIM: The diagnosis of mild or episodic Cushing's syndrome is difficult.
  • The standard tests include 24-hour urinary free cortisol (UFC), night-time blood, or salivary cortisol measurements, and dexamethasone suppression tests.
  • Imaging studies of the pituitary have not been recommended as part of the initial workup (only to help distinguish pituitary Cushing's disease from the ectopic ACTH syndrome) because of poor sensitivity and specificity.
  • With the development of dynamic pituitary MRI which uses multiple coronal dynamic sequences following gadolinium intravenous contrast, we hypothesized that the sensitivity and specificity would be increased and MRI would provide useful information for the initial diagnosis of Cushing's syndrome.
  • METHODS: This was a retrospective chart review examining charts from 87 consecutive patients who were evaluated for Cushing's syndrome in a tertiary Endocrinology clinic over a one-year period.
  • Most patients had mild and/or episodic hypercortisolism.
  • Of these patients, 24 eventually were diagnosed with pituitary Cushing's syndrome by biochemical testing (24-h UFC and urinary 17-hydroxycorticosteroids, 11 PM salivary cortisol measurements, evening plasma cortisol), and 22 had the diagnosis of Cushing's syndrome excluded.
  • Dynamic pituitary MRI (1.5 Tesla) was performed on all patients.
  • The reader of the MRI was blind to the diagnosis.
  • RESULTS: Twenty-three of 24 patients had a MRI consistent with a pituitary lesion (21 with a microadenoma, two with pituitary asymmetry).
  • In contrast, only 3 of 20 patients (2 patient did not have MRIs) in the Cushing's excluded group had a pituitary lesion on dynamic MRI.
  • Dynamic pituitary MRI had the highest sensitivity and negative predictive value of any testing modalities and its specificity and positive predictive value were similar to that of other tests.
  • CONCLUSION: We conclude that almost all patients in this series with Cushing's syndrome have a lesion on dynamic pituitary MRI, a rate much higher than the 50-60% rate reported for non-dynamic MRIs.
  • The false positive rate of 16% in our group of Cushing's excluded patients is similar to the literature value of 10% seen in normal volunteers and is acceptable since MRI is not used solely as a determinant for the diagnosis.
  • While a negative MRI will miss those patients with adrenal or ectopic Cushing's syndrome, those patients can usually be diagnosed by other testing.
  • Thus this preliminary study implies that dynamic pituitary MRI adds valuable information to assist in the diagnosis of Cushing's syndrome and should be ordered as part of the initial workup.
  • [MeSH-major] Cushing Syndrome / diagnosis. Magnetic Resonance Imaging / methods. Pituitary Gland / pathology

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  • (PMID = 17578763.001).
  • [ISSN] 0018-5043
  • [Journal-full-title] Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme
  • [ISO-abbreviation] Horm. Metab. Res.
  • [Language] eng
  • [Grant] United States / NCRR NIH HHS / RR / R25 RR019488; United States / NIGMS NIH HHS / GM / S06 GM068510; United States / NICHD NIH HHS / HD / U54 HD41748; United States / NCRR NIH HHS / RR / U54 RR14616
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] Germany
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21. Czirják S: [Minimally invasive surgery of the pituitary and the sellar region]. Orv Hetil; 2006 Aug 20;147(33):1545-57
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  • [Title] [Minimally invasive surgery of the pituitary and the sellar region].
  • [Transliterated title] A hypophysis és környéke minimálisan invazív sebészetének lehetoségei.
  • INTRODUCTION: New minimal invasive neurosurgical approaches for the treatment of diseases in the sellar and perisellar regions (superciliary and paraseptal approach, perioperative ACTH measurements, application of endoscopes and neuronavigation) were introduced by the author.
  • The study on perioperative plasma ACTH simultaneous measurements with rapid and standard methods revealed first in the literature that, during anaesthesia in patients with ACTH producing adenoma the plasma ACTH level changed individually.
  • There was no difference between arterial and venous plasma ACTH concentration in the same patient and the ACTH concentration in the bleedings from the peripituitary bony structures are individually variable, representing the network of the venous outflow of the pituitary.
  • The decrease in the plasma ACTH concentrations in the peripheral venous samples two hours after operation and next morning proved the radical removal of the adenoma.
  • The differences between concentrations in the left and right sides indicate the intrapituitary lateralization of the adenoma.
  • CONCLUSIONS: With the advent of the minimal invasive methods in surgery of the pituitary and the sellar region the mortality end the morbidity of the operations decreased.
  • [MeSH-major] Adenoma / surgery. Hypophysectomy / methods. Pituitary ACTH Hypersecretion / surgery. Pituitary Gland / surgery. Pituitary Neoplasms / surgery. Sella Turcica / surgery
  • [MeSH-minor] Adrenocorticotropic Hormone / blood. Adult. Blood Loss, Surgical / prevention & control. Cerebral Angiography. Child. Critical Care. Female. Humans. Length of Stay. Magnetic Resonance Imaging. Male. Middle Cerebral Artery / radiography. Minimally Invasive Surgical Procedures / methods. Treatment Outcome

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  • (PMID = 17037677.001).
  • [ISSN] 0030-6002
  • [Journal-full-title] Orvosi hetilap
  • [ISO-abbreviation] Orv Hetil
  • [Language] hun
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Hungary
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
  • [Number-of-references] 49
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22. Starkman MN, Giordani B, Gebarski SS, Schteingart DE: Improvement in mood and ideation associated with increase in right caudate volume. J Affect Disord; 2007 Aug;101(1-3):139-47
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  • BACKGROUND: The basal ganglia, particularly caudate, are hypothesized to play a role in affective and obsessive-compulsive disorders.
  • The depressive syndrome is a feature of untreated Cushing's disease.
  • The objective of this study was to test the hypothesis that after treatment of Cushing's disease reduces elevated cortisol, improvement in mood and related ideations are associated with increase in caudate volume.
  • METHODS: In this longitudinal, interventional study of 23 patients with Cushing's disease, 24-hour urinary free cortisol, structural magnetic resonance imaging and behavioral measures were obtained prior to treatment and approximately one year after pituitary microadenomectomy.
  • Although most likely not diminishing the significant findings, less sensitive methodology could lead to an increased probability of a type 2 error.
  • [MeSH-major] Affect / physiology. Caudate Nucleus / pathology. Depressive Disorder / psychology. Dominance, Cerebral / physiology. Image Processing, Computer-Assisted. Magnetic Resonance Imaging. Pituitary ACTH Hypersecretion / psychology. Postoperative Complications / psychology
  • [MeSH-minor] Adenoma / diagnosis. Adenoma / psychology. Adenoma / surgery. Adult. Anxiety Disorders / diagnosis. Anxiety Disorders / physiopathology. Anxiety Disorders / psychology. Female. Hippocampus / pathology. Humans. Hydrocortisone / urine. Longitudinal Studies. Male. Middle Aged. Obsessive-Compulsive Disorder / diagnosis. Obsessive-Compulsive Disorder / physiopathology. Obsessive-Compulsive Disorder / psychology. Personality Inventory. Pituitary Neoplasms / diagnosis. Pituitary Neoplasms / psychology. Pituitary Neoplasms / surgery

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  • (PMID = 17174404.001).
  • [ISSN] 0165-0327
  • [Journal-full-title] Journal of affective disorders
  • [ISO-abbreviation] J Affect Disord
  • [Language] eng
  • [Grant] United States / NCRR NIH HHS / RR / M01 RR00042; United States / NIDDK NIH HHS / DK / R01-DK51337; United States / NIMH NIH HHS / MH / R01-MH43372
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] Netherlands
  • [Chemical-registry-number] WI4X0X7BPJ / Hydrocortisone
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23. Kale SB, Saksena DS, Kole SD, Agnihotri YC: Carcinoid tumors of the thymus. Asian Cardiovasc Thorac Ann; 2006 Apr;14(2):e30-2
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  • Twenty-five cases of neuroendocrine carcinoma of the thymus associated with Cushing's syndrome have been reported since 1972.(1) We report two new cases of thymic carcinoid, one of which presented with Cushing's disease.
  • [MeSH-minor] Adult. Cushing Syndrome / etiology. Humans. Male. Middle Aged

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  • (PMID = 16551806.001).
  • [ISSN] 1816-5370
  • [Journal-full-title] Asian cardiovascular & thoracic annals
  • [ISO-abbreviation] Asian Cardiovasc Thorac Ann
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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24. Tateno T, Kato M, Tani Y, Yoshimoto T, Oki Y, Hirata Y: Processing of high-molecular-weight form adrenocorticotropin in human adrenocorticotropin-secreting tumor cell line (DMS-79) after transfection of prohormone convertase 1/3 gene. J Endocrinol Invest; 2010 Feb;33(2):113-7
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  • Ectopic ACTH-producing tumors preferentially secrete biologically inactive ACTH precursors and ACTH-related fragments.
  • DMS-79 is known to secrete unprocessed high-molecular-weight (HMW) form ACTH.
  • Molecular weights of ACTH-related peptides were determined by chromatographical analyses coupled with ACTH and beta-endorphin (beta-END) radioimmunoassays.
  • The steady-state mRNA levels of PC1/3 and 2 in DMS-79 were lower than those in ACTH-secreting and nonfunctioning pituitary tumors.
  • DMS-79 predominantly secreted HMW form with both ACTH and beta-END immunoreactivities by size-exclusion chromatography.
  • After purification by immunoaffinity chromatography with anti-ACTH antibody, the apparent molecular weight of HMW form ACTH was estimated to be 16 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis with silver staining.
  • After retroviral transfection of PC1/3 cDNA into DMS-79 and puromycin selection, PC1/3 stably-expressing cell line (DMS-79T) secreted two immunoreactive ACTH components, a major one coeluting with ACTH(1-39) and a minor one as a HMW form as well as two beta- END immunoreactive components coeluting with beta-lipotropic hormone and beta-END, respectively.
  • Thus, we have established PC1/3 stably-expressing cell line (DMS-79T) capable of proteolytically processing ACTH precursor molecule(s) into mature ACTH and beta-END.
  • [MeSH-major] Adrenocorticotropic Hormone / biosynthesis. Adrenocorticotropic Hormone / secretion. Gene Expression. Pro-Opiomelanocortin / metabolism. Proprotein Convertase 1 / genetics
  • [MeSH-minor] Adenoma / secretion. Cell Line, Tumor. Electrophoresis, Polyacrylamide Gel. Humans. Lung Neoplasms. Molecular Weight. Pituitary Neoplasms / secretion. Proprotein Convertase 2 / genetics. Proprotein Convertase 2 / metabolism. RNA, Messenger / analysis. Retroviridae / genetics. Small Cell Lung Carcinoma. Transfection. beta-Endorphin / metabolism

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  • (PMID = 19786827.001).
  • [ISSN] 1720-8386
  • [Journal-full-title] Journal of endocrinological investigation
  • [ISO-abbreviation] J. Endocrinol. Invest.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Italy
  • [Chemical-registry-number] 0 / RNA, Messenger; 60617-12-1 / beta-Endorphin; 66796-54-1 / Pro-Opiomelanocortin; 9002-60-2 / Adrenocorticotropic Hormone; EC 3.4.21.93 / Proprotein Convertase 1; EC 3.4.21.94 / Proprotein Convertase 2
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25. Storr HL, Afshar F, Matson M, Sabin I, Davies KM, Evanson J, Plowman PN, Besser GM, Monson JP, Grossman AB, Savage MO: Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing's disease. Eur J Endocrinol; 2005 Jun;152(6):825-33
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  • [Title] Factors influencing cure by transsphenoidal selective adenomectomy in paediatric Cushing's disease.
  • OBJECTIVE: Early diagnosis and effective treatment of paediatric Cushing's disease (CD) is necessary to minimise associated morbidity.
  • Sixteen patients (59%), seven males and nine females (mean age+/-s.d., 14.2+/-2.5 yr; range, 8.2-17.8 yr), were cured (post-operative serum cortisol < 50 nM).
  • Eleven patients, nine males and two females (mean age+/-s.d., 11.5+/-3.6 yr; range, 6.4-17.8 yr) had post-operative cortisol levels above 50 nM (2-20 days), with mean serum cortisol levels at 09:00 h of 537 nM (range 269-900 nM) indicating a lack of cure.
  • These 11 patients received external beam pituitary radiotherapy (RT).
  • One patient with a pituitary macroadenoma had a post-operative cortisol level of < 50 nM but 0.8 yr later showed an elevated cortisol and residual disease.
  • All patients had CT/MRI pituitary imaging: 14 were reported to have microadenomas and one macroadenoma, while 12 were reported as normal.
  • Bilateral simultaneous inferior petrosal sinus sampling (BSIPSS) with i.v. corticotropin-releasing hormone (CRH) administration was introduced as a pre-operative investigation in 1986 and was performed in 21 patients (78%), on BSIPSS, 16 (76%) had evidence suggesting pituitary adrenocorticotropic hormone (ACTH) secretion (central to peripheral (IPS:P) ACTH ratio after CRH of > or = 3.0) and 16 (76%) showed lateralisation of ACTH secretion (IPSG of > or = 1.4).
  • There was concordance between the BSIPSS finding and the position of the microadenoma at surgery in 17/21 (81%) patients.
  • Of the 16 patients showing lateralisation of ACTH secretion, 12 (75%) were cured by TSS.
  • Of the four without lateralisation of ACTH, suggesting a midline lesion, 3 (75%) were cured by TSS.
  • Post-operative pituitary hormone deficiencies in the patients cured by TSS were: pan-hypopituitarism 1/16, isolated growth hormone deficiency (GHD) (peak GH on glucagon/ITT < 1-17.9 mU/l) 9/16 and diabetes insipidus 3/16.
  • Introduction of BSIPSS resulted in the demonstration of a high rate of lateralisation of ACTH secretion consistent with the surgical identification of the adenoma, and therefore appears likely to have contributed to the higher surgical cure rate.

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  • (PMID = 15941921.001).
  • [ISSN] 0804-4643
  • [Journal-full-title] European journal of endocrinology
  • [ISO-abbreviation] Eur. J. Endocrinol.
  • [Language] ENG
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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26. Santos S, Santos E, Gaztambide S, Salvador J: [Diagnosis and differential diagnosis of Cushing's syndrome]. Endocrinol Nutr; 2009 Feb;56(2):71-84
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  • [Title] [Diagnosis and differential diagnosis of Cushing's syndrome].
  • [Transliterated title] Diagnóstico y diagnóstico diferencial del síndrome de Cushing.
  • Because of the variability in the clinical expression of Cushing's syndrome, different biochemical tests and imaging techniques must be used for effective diagnosis and treatment.
  • The clinical history is important to assess the general impact of hypercortisolism on organs and systems, as well as to guide suspicion toward more aggressive entities such as overt ectopic ACTH syndrome or to detect an iatrogenic etiology of Cushing's syndrome.
  • The screening phase relies on tests that are sensitive but not specific, such as urinary free cortisol, nocturnal salivary cortisol and 1 mg dexamethasone suppression, which still require established assessment criteria.
  • Confirmation can be obtained by repeating urinary cortisol, 2 mg/day dexamethasone suppression, both alone and combined with corticotropin releasing hormone (CRH), to exclude pseudoCushing states.
  • ACTH dependency can be easily explored by ACTH measurements, but the differential diagnosis between pituitary and ectopic Cushing's disease is difficult and may require invasive procedures such as inferior petrosal sinus sampling.
  • Sophisticated imaging and isotopic techniques play a significant role in locating the source of ACTH in ectopic syndromes but are not always effective.
  • In general, biochemical and imaging tests should be combined in order to assess different mechanisms and perspectives of the syndrome.
  • Rigorous methodology is essential to obtain accurate results, allowing a correct diagnosis and improving therapeutic performance in this devastating disease.
  • [MeSH-major] Cushing Syndrome / diagnosis
  • [MeSH-minor] ACTH Syndrome, Ectopic / complications. ACTH Syndrome, Ectopic / diagnosis. Adenoma / complications. Adenoma / diagnosis. Adenoma / secretion. Adrenal Cortex Neoplasms / complications. Adrenal Cortex Neoplasms / diagnosis. Adrenal Cortex Neoplasms / secretion. Adrenocorticotropic Hormone / blood. Circadian Rhythm. Corticotropin-Releasing Hormone. Deamino Arginine Vasopressin. Dexamethasone / administration & dosage. Diagnosis, Differential. Diagnostic Imaging. Humans. Hydrocortisone / analysis. Hydrocortisone / secretion. Hypothalamo-Hypophyseal System / physiopathology. Petrosal Sinus Sampling. Pituitary ACTH Hypersecretion / complications. Pituitary ACTH Hypersecretion / diagnosis. Pituitary Neoplasms / complications. Pituitary Neoplasms / diagnosis. Pituitary Neoplasms / secretion. Pituitary-Adrenal System / physiopathology. Saliva / chemistry

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  • (PMID = 19627715.001).
  • [ISSN] 1575-0922
  • [Journal-full-title] Endocrinología y nutrición : órgano de la Sociedad Española de Endocrinología y Nutrición
  • [ISO-abbreviation] Endocrinol Nutr
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article; Review
  • [Publication-country] Spain
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; 9015-71-8 / Corticotropin-Releasing Hormone; ENR1LLB0FP / Deamino Arginine Vasopressin; WI4X0X7BPJ / Hydrocortisone
  • [Number-of-references] 54
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27. Atkinson AB, Kennedy A, Wiggam MI, McCance DR, Sheridan B: Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance. Clin Endocrinol (Oxf); 2005 Nov;63(5):549-59
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  • [Title] Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance.
  • OBJECTIVE: There have been a few reports on long-term remission rates after apparent early remission following pituitary surgery in the management of Cushing's disease.
  • An undetectable postoperative serum cortisol has been regarded as the result most likely to predict long-term remission.
  • Our objective was to assess the relapse rates in patients who underwent transsphenoidal surgery in order to determine whether undetectable cortisol following surgery was predictive of long-term remission and whether it was possible to have long-term remission when early morning cortisol was measurable but not grossly elevated.
  • PATIENTS: We reviewed the long-term outcome in 63 patients who had pituitary surgery for the treatment of Cushing's disease between 1979 and 2000.
  • Our usual practice was that early after the operation, an 08:00 h serum cortisol was measured 24 h after the last dose of hydrocortisone.
  • Current clinical status and recent 24-h urinary free cortisol values were used as an index of activity of the Cushing's disease.
  • In many patients, sequential collections of early morning urine specimens for urinary cortisol to creatinine ratio were also performed in an attempt to diagnose cyclical and intermittent forms of recurrent hypercortisolism.
  • RESULTS: Mean age at diagnosis was 40.3 years (range 14-70 years).
  • Of these 45 patients, four have subsequently died while in remission from hypercortisolism.
  • Of those 10, six demonstrated definite cyclical cortisol secretion.
  • Two of the 10 had undetectable basal serum cortisol levels in the immediate postoperative period.
  • Fourteen (45%) of the 31 who remained in remission had detectable serum cortisol levels (> 50 nmol/l) immediately postoperatively, and remain in remission after a mean of 8.8 years.
  • CONCLUSIONS: The overall remission rate of 56% (35/63) at 9.6 years follow-up is disappointing and merits some re-appraisal of the widely accepted principle that pituitary surgery must be the initial treatment of choice in pituitary-dependent Cushing's syndrome.
  • Following pituitary surgery, careful ongoing expert endocrine assessment is mandatory as the incidence of relapse increases with time and also with increasing rigour of the endocrine evaluation.
  • A significant number of our patients were shown to have relapsed with a cyclical form of hypercortisolism.
  • [MeSH-major] Cushing Syndrome / surgery. Hypophysectomy
  • [MeSH-minor] Adolescent. Adrenocorticotropic Hormone / blood. Adult. Aged. Biomarkers / blood. Dexamethasone. Female. Follow-Up Studies. Humans. Hydrocortisone / blood. Male. Middle Aged. Recurrence. Remission Induction. Treatment Outcome

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  • (PMID = 16268808.001).
  • [ISSN] 0300-0664
  • [Journal-full-title] Clinical endocrinology
  • [ISO-abbreviation] Clin. Endocrinol. (Oxf)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers; 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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28. Azezli AD, Bayraktaroglu T, Ece T, Kutluturk F, Orhan Y: Static lung volumes in patients with Cushing's disease. Exp Clin Endocrinol Diabetes; 2008 Jan;116(1):53-7
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  • [Title] Static lung volumes in patients with Cushing's disease.
  • OBJECTIVE: Numerous clinical manifestations have been described in association with Cushing's syndrome.
  • There are no eligible data on pulmonary function tests in Cushing's disease (CD).
  • MATERIALS AND METHODS: This cross-sectional study comprised 10 patients with Cushing's disease (F/M, 9/1).
  • Disease duration and cortisol concentrations by HDDSTs were negatively correlated with predicted FEV1/FVC values and the percentage of predicted FEV1 ratios, respectively.
  • DISCUSSION: The lung volume and ventilatory performance by spirometry were not disturbed in patients with endogenous hypercostisolism due to Cushing's disease.
  • [MeSH-major] Lung Volume Measurements. Pituitary ACTH Hypersecretion / physiopathology

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  • (PMID = 17973213.001).
  • [ISSN] 0947-7349
  • [Journal-full-title] Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association
  • [ISO-abbreviation] Exp. Clin. Endocrinol. Diabetes
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] WI4X0X7BPJ / Hydrocortisone
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29. Kidambi S, Raff H, Findling JW: Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome. Eur J Endocrinol; 2007 Dec;157(6):725-31
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  • [Title] Limitations of nocturnal salivary cortisol and urine free cortisol in the diagnosis of mild Cushing's syndrome.
  • OBJECTIVE: Cushing's syndrome (CS) is difficult to diagnose due to its nonspecific presentation.
  • Diagnostic tests like 24-h urine free cortisol (UFC) and the overnight 1 mg dexamethasone suppression test (DST) lack sufficient sensitivity and specificity.
  • Measurement of nocturnal salivary cortisol (NSC) is an accurate and reproducible test with a high sensitivity for CS.
  • We present 11 cases of CS with normal or mildly elevated UFC in whom NSC was helpful in making a diagnosis.
  • Imaging studies included magnetic resonance imaging (MRI) of pituitary or computer tomography scan of abdomen.
  • Out of eleven patients, six had an abnormality in the pituitary gland found by MRI and two out of eleven had adrenal masses.
  • The remaining three had normal pituitary MRI but had inferior petrosal sinus (IPS) sampling indicating Cushing's disease.
  • All patients had appropriate surgery, and histopathology of all except one was suggestive of either a cortisol-producing adrenal adenoma or an ACTH-secreting pituitary adenoma.
  • Multiple samples (urine/saliva) and DST are needed to make the diagnosis of mild CS.

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  • (PMID = 18057379.001).
  • [ISSN] 1479-683X
  • [Journal-full-title] European journal of endocrinology
  • [ISO-abbreviation] Eur. J. Endocrinol.
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; WI4X0X7BPJ / Hydrocortisone
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30. Jensen RL, Jensen PR, Shrieve AF, Hazard L, Shrieve DC: Overall and progression-free survival and visual and endocrine outcomes for patients with parasellar lesions treated with intensity-modulated stereotactic radiosurgery. J Neurooncol; 2010 Jun;98(2):221-31
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  • Six patients with cavernous sinus meningiomas and eight with recurrent pituitary adenomas were treated.
  • Three of the pituitary tumors were hormonally active (two with Cushing disease, one with acromegaly).
  • [MeSH-major] Disease-Free Survival. Endocrine System Diseases / etiology. Meningeal Neoplasms / surgery. Pituitary Neoplasms / surgery. Radiosurgery / adverse effects. Vision Disorders / etiology

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  • (PMID = 20461446.001).
  • [ISSN] 1573-7373
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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31. Smith PW, Turza KC, Carter CO, Vance ML, Laws ER, Hanks JB: Bilateral adrenalectomy for refractory Cushing disease: a safe and definitive therapy. J Am Coll Surg; 2009 Jun;208(6):1059-64
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  • [Title] Bilateral adrenalectomy for refractory Cushing disease: a safe and definitive therapy.
  • BACKGROUND: Refractory Cushing disease (CD) is associated with considerable morbidity and mortality.
  • All patients achieved clinical reversal of hypercortisolism, including the 5 (13%) with ectopic adrenal tissue.
  • Elevated serum ACTH (> 200 ng/mL) was present during followup in 33% (13 of 40).
  • [MeSH-major] Adrenalectomy / methods. Pituitary ACTH Hypersecretion / surgery
  • [MeSH-minor] ACTH-Secreting Pituitary Adenoma / surgery. Adenoma / surgery. Adult. Aged. Female. Humans. Male. Middle Aged. Retrospective Studies. Treatment Outcome. Young Adult

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  • (PMID = 19476892.001).
  • [ISSN] 1879-1190
  • [Journal-full-title] Journal of the American College of Surgeons
  • [ISO-abbreviation] J. Am. Coll. Surg.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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32. Sieber-Ruckstuhl NS, Boretti FS, Wenger M, Maser-Gluth C, Reusch CE: Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane. Vet Rec; 2008 Oct 18;163(16):477-81
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  • [Title] Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane.
  • The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH).
  • In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane.
  • The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs.
  • During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly.
  • The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol.
  • [MeSH-major] Adrenocortical Hyperfunction / veterinary. Cortisone / blood. Dihydrotestosterone / analogs & derivatives. Dog Diseases / drug therapy. Enzyme Inhibitors / administration & dosage. Hydrocortisone / blood
  • [MeSH-minor] Adrenocorticotropic Hormone. Animals. Case-Control Studies. Dogs. Female. Hormones. Male. Pituitary Diseases / blood. Pituitary Diseases / veterinary. Pituitary Gland. Statistics, Nonparametric

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  • (PMID = 18931355.001).
  • [ISSN] 0042-4900
  • [Journal-full-title] The Veterinary record
  • [ISO-abbreviation] Vet. Rec.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Enzyme Inhibitors; 0 / Hormones; 08J2K08A3Y / Dihydrotestosterone; 9002-60-2 / Adrenocorticotropic Hormone; L0FPV48Q5R / trilostane; V27W9254FZ / Cortisone; WI4X0X7BPJ / Hydrocortisone
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33. Suda T, Kageyama K, Nigawara T, Sakihara S: Evaluation of diagnostic tests for ACTH-dependent Cushing's syndrome. Endocr J; 2009;56(3):469-76
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  • [Title] Evaluation of diagnostic tests for ACTH-dependent Cushing's syndrome.
  • We evaluated the usefulness and accuracy of diagnostic tests for adrenocorticotropic hormone (ACTH)- dependent Cushing's syndrome, based on our experience of 88 cases, including 73 cases with Cushing's disease, and 15 cases with ectopic ACTH syndrome (EAS).
  • In our study, 0.5 mg of dexamethasone failed to suppress the morning cortisol secretion in 100% of cases with Cushing's disease and EAS.
  • Plasma ACTH levels were significantly increased by desmopressin (DDAVP) in 86% of cases with Cushing's disease, especially in microadenomas (90%), while these levels were not affected in normal subjects.
  • Plasma ACTH levels were increased in response to the human corticotropin-releasing hormone (CRH) test in 100% of microadenomas and 73% of macroadenomas with Cushing's disease, but only in 27% of cases with EAS.
  • A high dose (8 mg) of dexamethasone suppressed the morning cortisol secretion in 89% of microadenomas with Cushing's disease, and in 82% of all cases with Cushing's disease, while it did in only 20% of cases with EAS.
  • Taken together, the 0.5 mg dexamethasone suppression test (DST) and DDAVP test are considerably useful for the screening of ACTH-dependent Cushing's syndrome.
  • The CRH test and 8 mg DST would be effective for the diagnosis of Cushing's diseases, because our study shows a sensitivity of 81% in cases with Cushing's disease when these tests are considered together.
  • These data were submitted to prepare the diagnostic criteria for Cushing's disease, suggested by the working group of the Ministry of Health, Labour, and Welfare of Japan.
  • [MeSH-major] ACTH Syndrome, Ectopic / diagnosis. Adrenocorticotropic Hormone / blood. Cushing Syndrome / diagnosis
  • [MeSH-minor] Circadian Rhythm. Corticotropin-Releasing Hormone. Deamino Arginine Vasopressin. Dexamethasone. Diagnosis, Differential. Humans. Sensitivity and Specificity

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  • (PMID = 19225213.001).
  • [ISSN] 1348-4540
  • [Journal-full-title] Endocrine journal
  • [ISO-abbreviation] Endocr. J.
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; 9015-71-8 / Corticotropin-Releasing Hormone; ENR1LLB0FP / Deamino Arginine Vasopressin
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34. Psaras T, Milian M, Hattermann V, Gallwitz B, Freiman T, Honegger J: Aftercare in patients with Cushing's disease and acromegaly: is there room for improvement? Acta Neurochir (Wien); 2010 Feb;152(2):271-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Aftercare in patients with Cushing's disease and acromegaly: is there room for improvement?
  • PURPOSE: Evaluation of aftercare, medical therapy and remission rate for Cushing's disease (CD) and acromegaly (AC).
  • The patients received a disease-related questionnaire and were invited for a follow-up at the outpatient clinic of the Department of Neurosurgery.
  • [MeSH-major] Acromegaly / drug therapy. Aftercare / methods. Aftercare / statistics & numerical data. Pituitary ACTH Hypersecretion / drug therapy. Quality Assurance, Health Care / methods
  • [MeSH-minor] Adenoma / complications. Adenoma / surgery. Adult. Aged. Biomarkers / analysis. Biomarkers / metabolism. Cross-Sectional Studies. Endocrinology / methods. Endocrinology / statistics & numerical data. Female. Human Growth Hormone / analogs & derivatives. Human Growth Hormone / therapeutic use. Humans. Insulin-Like Growth Factor I / analysis. Insulin-Like Growth Factor I / metabolism. Male. Middle Aged. Neurosurgery / statistics & numerical data. Neurosurgical Procedures. Octreotide / therapeutic use. Outcome Assessment (Health Care). Peptides, Cyclic / therapeutic use. Pituitary Neoplasms / complications. Pituitary Neoplasms / surgery. Recurrence. Somatostatin / analogs & derivatives. Somatostatin / therapeutic use. Surveys and Questionnaires

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  • (PMID = 19911113.001).
  • [ISSN] 0942-0940
  • [Journal-full-title] Acta neurochirurgica
  • [ISO-abbreviation] Acta Neurochir (Wien)
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Austria
  • [Chemical-registry-number] 0 / Biomarkers; 0 / Peptides, Cyclic; 0 / pegvisomant; 118992-92-0 / lanreotide; 12629-01-5 / Human Growth Hormone; 51110-01-1 / Somatostatin; 67763-96-6 / Insulin-Like Growth Factor I; RWM8CCW8GP / Octreotide
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35. Haritou SJ, Zylstra R, Ralli C, Turner S, Tortonese DJ: Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod. J Neuroendocrinol; 2008 Aug;20(8):988-96
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  • [Title] Seasonal changes in circadian peripheral plasma concentrations of melatonin, serotonin, dopamine and cortisol in aged horses with Cushing's disease under natural photoperiod.
  • Equine pituitary pars intermedia dysfunction (PPID) is a common and serious condition that gives rise to Cushing's disease.
  • In the older horse, it results in hyperadrenocorticism and disrupted energy metabolism, the severity of which varies with the time of year.
  • To gain insight into the mechanism of its pathogenesis, 24-h profiles for peripheral plasma melatonin, serotonin, dopamine and cortisol concentrations were determined at the winter and summer solstices, and the autumn and spring equinoxes in six horses diagnosed with Cushing's disease and six matched controls.
  • The plasma concentrations of cortisol did not show seasonal variation and were different in diseased horses only in the summer when they were higher across the entire 24-h period (P < 0.05).
  • By contrast, dopamine output showed seasonal variation and was significantly lower in the Cushing's group in the summer and autumn (P < 0.05).
  • The finding that the profiles of circulating melatonin are similar in Cushingoid and control horses reveals that the inability to read time of year by animals suffering from Cushing's syndrome is an unlikely reason for the disease.
  • [MeSH-major] Aging / blood. Dopamine / blood. Horses / blood. Hydrocortisone / blood. Melatonin / blood. Pituitary ACTH Hypersecretion / blood. Serotonin / blood

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  • (PMID = 18540997.001).
  • [ISSN] 1365-2826
  • [Journal-full-title] Journal of neuroendocrinology
  • [ISO-abbreviation] J. Neuroendocrinol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 333DO1RDJY / Serotonin; JL5DK93RCL / Melatonin; VTD58H1Z2X / Dopamine; WI4X0X7BPJ / Hydrocortisone
  • [Other-IDs] NLM/ PMC2658710
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36. Illouz F, Dubois-Ginouves S, Laboureau S, Rohmer V, Rodien P: [Use of cabergoline in persisting Cushing's disease]. Ann Endocrinol (Paris); 2006 Sep;67(4):353-6
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  • [Title] [Use of cabergoline in persisting Cushing's disease].
  • [Transliterated title] Utilisation de la cabergoline dans la maladie de Cushing non contrôlée.
  • Cabergoline is a dopaminergic agonist with demonstrated efficiency of for the treatment of prolactin-secreting pituitary tumors.
  • It has also been reported effective for patients with hypercortisolism uncontrolled by conventional therapies.
  • We describe the use of cabergoline in three patients with Cushing's disease, one of them presenting a silent ACTH-secreting pituitary tumor.
  • However persisting hypercortisolism motivated the use of cabergoline.
  • We describe a decrease or a normalization in hypercortisolism; for one of the subjects, tumor growth seemed to be stopped.
  • While cabergoline can induce a suppression of cortisol secretion or a corticotroph tumor shrinkage, the sites of action remain unclear.
  • [MeSH-major] Adrenocortical Hyperfunction / drug therapy. Ergolines / therapeutic use. Pituitary ACTH Hypersecretion / diagnosis

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  • (PMID = 17072242.001).
  • [ISSN] 0003-4266
  • [Journal-full-title] Annales d'endocrinologie
  • [ISO-abbreviation] Ann. Endocrinol. (Paris)
  • [Language] fre
  • [Publication-type] Case Reports; English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Dopamine Agonists; 0 / Ergolines; LL60K9J05T / cabergoline; WI4X0X7BPJ / Hydrocortisone
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37. Vilar L, Freitas Mda C, Lima LH, Lyra R, Kater CE: Cushing's syndrome in pregnancy: an overview. Arq Bras Endocrinol Metabol; 2007 Nov;51(8):1293-302
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  • [Title] Cushing's syndrome in pregnancy: an overview.
  • Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature.
  • Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease.
  • The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH.
  • Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur.
  • Therefore, the diagnosis of CS during pregnancy is much more difficult.
  • Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes.
  • Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical.
  • [MeSH-major] Cushing Syndrome / diagnosis. Pregnancy / metabolism. Pregnancy Complications / diagnosis
  • [MeSH-minor] Diabetes, Gestational / diagnosis. Diagnosis, Differential. Female. Humans. Hypothalamo-Hypophyseal System / physiopathology. Pre-Eclampsia / diagnosis. Pregnancy Outcome


38. Draper N, Stewart PM: 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action. J Endocrinol; 2005 Aug;186(2):251-71
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  • [Title] 11beta-hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action.
  • Two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1 and 11beta-HSD2) catalyse the interconversion of hormonally active cortisol and inactive cortisone.
  • The enzyme evolved from a metabolic pathway to a novel mechanism underpinning human disease with the elucidation of the role of the type 2 or 'kidney' isozyme and an inherited form of hypertension, 'apparent mineralocorticoid excess'.
  • 'Cushing's disease of the kidney' arises because of a failure of 11beta-HSD2 to inactivate cortisol to cortisone resulting in cortisol-induced mineralocorticoid excess.Conversely, 11beta-HSD1 has been linked to human obesity and insulin resistance, but also to other diseases in which glucocorticoids have historically been implicated (osteoporosis, glaucoma).
  • Here, the activation of cortisol from cortisone facilitates glucocorticoid hormone action at an autocrine level.

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  • (PMID = 16079253.001).
  • [ISSN] 0022-0795
  • [Journal-full-title] The Journal of endocrinology
  • [ISO-abbreviation] J. Endocrinol.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] EC 1.1.1.146 / 11-beta-Hydroxysteroid Dehydrogenase Type 1; EC 1.1.1.146 / 11-beta-Hydroxysteroid Dehydrogenase Type 2; EC 1.1.1.146 / 11-beta-Hydroxysteroid Dehydrogenases; V27W9254FZ / Cortisone; WI4X0X7BPJ / Hydrocortisone
  • [Number-of-references] 182
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39. Hornyak M, Weiss MH, Nelson DH, Couldwell WT: Nelson syndrome: historical perspectives and current concepts. Neurosurg Focus; 2007;23(3):E12
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  • [Title] Nelson syndrome: historical perspectives and current concepts.
  • The appearance of an adrenocorticotropic hormone (ACTH)-producing tumor after bilateral adrenalectomy for Cushing disease was first described by Nelson in 1958.
  • The syndrome that now bears his name was characterized by hyperpigmentation, a sellar mass, and increased plasma ACTH levels.
  • The treatment of Cushing disease has changed drastically since the 1950s, when the choice was adrenalectomy.
  • Thus, the occurrence, diagnosis, and treatment of Nelson syndrome have changed as well.
  • In the modern era of high-resolution neuroimaging, transsphenoidal microneurosurgery, and stereotactic radiosurgery, Nelson syndrome has become a rare entity.
  • The authors describe the history of the diagnosis and treatment of Nelson syndrome.
  • In light of the changes described, the authors believe this disease must be reevaluated in the contemporary era and a modern paradigm adopted.
  • [MeSH-major] Nelson Syndrome / history

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  • (PMID = 17961024.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Biography; Historical Article; Journal Article; Portraits
  • [Publication-country] United States
  • [Personal-name-as-subject] Nelson DH
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40. Kawashima ST, Usui T, Sano T, Iogawa H, Hagiwara H, Tamanaha T, Tagami T, Naruse M, Hojo M, Takahashi JA, Shimatsu A: P53 gene mutation in an atypical corticotroph adenoma with Cushing's disease. Clin Endocrinol (Oxf); 2009 Apr;70(4):656-7
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  • [Title] P53 gene mutation in an atypical corticotroph adenoma with Cushing's disease.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / complications. ACTH-Secreting Pituitary Adenoma / genetics. Adenoma / genetics. Mutation / genetics. Pituitary ACTH Hypersecretion / etiology. Pituitary Neoplasms / genetics. Tumor Suppressor Protein p53 / genetics

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  • (PMID = 18771563.001).
  • [ISSN] 1365-2265
  • [Journal-full-title] Clinical endocrinology
  • [ISO-abbreviation] Clin. Endocrinol. (Oxf)
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Tumor Suppressor Protein p53
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41. Yavuz N: Laparoscopic transperitoneal adrenalectomy using the LigaSure vessel sealing system. J Laparoendosc Adv Surg Tech A; 2005 Dec;15(6):591-5
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  • Indications for surgery were non-functioning adenoma (n = 10), pheochromocytoma (n = 4), Cushing's syndrome (n = 5), Conn's syndrome (n = 2), and lymphoma (n = 1).
  • The operative time for the patient with Cushing's disease in whom a bilateral adrenalectomy was performed was 180 minutes.
  • Wound infections developed in two patients with Cushing's syndrome.
  • Histopathologic examination of specimens revealed a cortex adenoma in 16 cases (10 of which was nonfunctional), a pheochromocytoma in 4 cases, a bilateral cortical hyperplasia in 1 case, and a lymphoma in 1 case.

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  • [ErratumIn] J Laparoendosc Adv Surg Tech A. 2006 Aug;16(4):433
  • (PMID = 16366864.001).
  • [ISSN] 1092-6429
  • [Journal-full-title] Journal of laparoendoscopic & advanced surgical techniques. Part A
  • [ISO-abbreviation] J Laparoendosc Adv Surg Tech A
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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42. Toniato A, Boschin I, Bernante P, Opocher G, Guolo AM, Pelizzo MR, Mantero F: Laparoscopic adrenalectomy for pheochromocytoma: is it really more difficult? Surg Endosc; 2007 Aug;21(8):1323-6
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  • OBJECTIVE: Laparoscopic adrenalectomy (LA) has become the gold standard technique for almost all the adrenal masses, but several Authors still debate about LA in pheochromocytoma.
  • BACKGROUND: The purpose of this study was to compare feasibility and safety of LA for pheo and analyze the results relative to LA for incidentaloma, Conn's disease and Cushing's disease.
  • METHODS: Between January 1994 and March 2006, 167 LAs were carried out in 160 consecutive patients at our Department and 46 of them were affected by pheo, 60 by Conn's disease, 34 by adrenal incidentaloma and 20 by Cushing's disease.
  • RESULTS: Successful LA was performed in 159 out of 167 cases (95.2%).
  • LA for patients with Cushing's disease (average length of hospital stay and intraoperative blood loss, p < 0.023 and p > 0.002 respectively) and with adrenal incidentaloma (intraoperative blood loss p < 0.009) seems to be a more challenging procedure.
  • CONCLUSION: The evaluation of this relatively large monoinstitutional experience suggests that LA could be considered the most suitable method for removing pheochromocytoma.
  • [MeSH-minor] Adolescent. Adrenal Cortex Neoplasms / surgery. Adrenocortical Adenoma / surgery. Adult. Aged. Aged, 80 and over. Blood Loss, Surgical. Child. Female. Humans. Male. Middle Aged. Pituitary ACTH Hypersecretion / surgery


43. Walsh MT, Couldwell WT: Symptomatic cystic degeneration of a clinically silent corticotroph tumor of the pituitary gland. Skull Base; 2010 Sep;20(5):367-70
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  • [Title] Symptomatic cystic degeneration of a clinically silent corticotroph tumor of the pituitary gland.
  • Clinically silent corticotroph tumors of the pituitary gland are those tumors that stain for adrenocorticotropic hormone (ACTH) but do not manifest with clinical or laboratory features of Cushing disease.
  • These tumors have been described as exhibiting more aggressive behavior than other nonfunctional pituitary tumors.
  • We present an unusual case of a clinically silent corticotropic adenoma of the pituitary gland that underwent cystic degeneration following recurrence after transsphenoidal surgery and radiation therapy.
  • Patients with clinically silent ACTH-secreting tumors should be monitored for aggressive tumor behavior and may require closer follow-up than those patients harboring other nonfunctional tumors.

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  • [Cites] Nucleic Acids Res. 1983 Oct 25;11(20):7191-203 [6634412.001]
  • (PMID = 21359002.001).
  • [ISSN] 1532-0065
  • [Journal-full-title] Skull base : official journal of North American Skull Base Society ... [et al.]
  • [ISO-abbreviation] Skull Base
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Other-IDs] NLM/ PMC3023327
  • [Keywords] NOTNLM ; Cortisol / Cushing disease / adrenocorticotropic hormone / corticotroph cells / cystic degeneration / nonfunctional pituitary adenoma
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44. Sun DQ, Cheng JJ, Frazier JL, Batra S, Wand G, Kleinberg LR, Rigamonti D, Quinones-Hinojosa A, Salvatori R, Lim M: Treatment of pituitary adenomas using radiosurgery and radiotherapy: a single center experience and review of literature. Neurosurg Rev; 2010 Apr;34(2):181-9
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  • [Title] Treatment of pituitary adenomas using radiosurgery and radiotherapy: a single center experience and review of literature.
  • Fractionated radiotherapy (FRT) and gamma knife stereotactic radiosurgery (GKSRS) are used as adjuvant therapies to surgical resection for functional and non-functional pituitary adenomas, although their optimum role in the treatment algorithm, as well as long-term safety and efficacy, still awaits further study.
  • We report a single center experience with 33 patients with non-functional (16 patients), ACTH- (five patients), GH- (four patients), or prolactin-secreting (eight patients) tumors treated with FRT or SRS.
  • For GKSRS, the median dosage was 16 Gy for non-functional adenomas and 23 Gy for hormone-secreting tumors.
  • Biochemical control, defined as normalized hormone values in the absence of medical therapy, was achieved in five out of eight prolactinoma patients and two out of five patients with Cushing's disease, but none of the four patients with acromegaly.
  • These results are presented with a review of the relevant literature on the differential characteristics of FRT versus SRS in the treatment of functional and non-functional pituitary adenomas and validate postoperative irradiation as a potentially safe and effective means for tumor control.
  • [MeSH-major] Pituitary Neoplasms / radiotherapy. Pituitary Neoplasms / surgery. Radiosurgery / methods
  • [MeSH-minor] Adrenocorticotropic Hormone / blood. Adult. Aged. Aged, 80 and over. Disease Progression. Female. Follow-Up Studies. Hormones / blood. Human Growth Hormone / blood. Humans. Hypopituitarism / etiology. Magnetic Resonance Imaging. Male. Middle Aged. Postoperative Complications / epidemiology. Prolactin / blood. Radiometry. Retrospective Studies. Treatment Outcome. Vision Disorders / epidemiology. Vision Disorders / etiology. Visual Fields. Young Adult

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  • (PMID = 20838838.001).
  • [ISSN] 1437-2320
  • [Journal-full-title] Neurosurgical review
  • [ISO-abbreviation] Neurosurg Rev
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Hormones; 12629-01-5 / Human Growth Hormone; 9002-60-2 / Adrenocorticotropic Hormone; 9002-62-4 / Prolactin
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45. Yano S, Kawano T, Kudo M, Makino K, Nakamura H, Kai Y, Morioka M, Kuratsu J: Endoscopic endonasal transsphenoidal approach through the bilateral nostrils for pituitary adenomas. Neurol Med Chir (Tokyo); 2009 Jan;49(1):1-7
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  • [Title] Endoscopic endonasal transsphenoidal approach through the bilateral nostrils for pituitary adenomas.
  • The endoscopic endonasal transsphenoidal approach through the bilateral nostrils was evaluated for the treatment of pituitary adenoma.
  • In addition, neuronavigation and real-time hormone monitoring are used.
  • Tumor removal rate, endocrinological outcomes, and complications were retrospectively assessed in 194 patients with pituitary adenomas who underwent 213 procedures between December 2001 and March 2008.
  • Endocrinological remission was achieved in 20 of 26 growth hormone-secreting tumors of Knosp grades 0-2, 16 of 17 microprolactinomas, and 6 of 9 cases of pure Cushing's disease.
  • Postoperative complications were cerebrospinal fluid leakage in 9 cases, visual worsening in 5, anterior pituitary insufficiency in 5, and permanent diabetes insipidus in 2.
  • The use of neuronavigation or intraoperative hormone monitoring leads to improved surgical results.
  • [MeSH-major] Adenoma / surgery. Endoscopy / methods. Pituitary Neoplasms / surgery
  • [MeSH-minor] Acromegaly / etiology. Adolescent. Adult. Aged. Aged, 80 and over. Diabetes Insipidus / etiology. Female. Humans. Hypopituitarism / etiology. Male. Middle Aged. Nasal Cavity / surgery. Neuronavigation. Pituitary ACTH Hypersecretion / etiology. Pituitary ACTH Hypersecretion / surgery. Postoperative Complications / etiology. Prolactinoma / surgery. Remission Induction. Retrospective Studies. Sphenoid Bone / surgery. Subdural Effusion / etiology. Vision Disorders / etiology. Young Adult

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  • (PMID = 19168995.001).
  • [ISSN] 1349-8029
  • [Journal-full-title] Neurologia medico-chirurgica
  • [ISO-abbreviation] Neurol. Med. Chir. (Tokyo)
  • [Language] eng
  • [Publication-type] Case Reports; Evaluation Studies; Journal Article
  • [Publication-country] Japan
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46. Kulkarni KP, Kochar IS: Cushing disease presenting as arthritis. J Pediatr Endocrinol Metab; 2010 Jun;23(6):603-5
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  • [Title] Cushing disease presenting as arthritis.
  • Cushing's syndrome is an endocrine disorder caused by hypercortisolism.
  • Despite its varied clinical spectrum of presentation, Cushing's disease has not been reported to present as arthritis.
  • Moreover, keratilysis exfolitiva has not been described in Cushing disease.
  • We report a 12 year old male child with pituitary micro adenoma initially presenting as arthritis and developing keratilysis exfolitiva.
  • [MeSH-major] Arthritis, Juvenile / diagnosis. Cushing Syndrome / diagnosis
  • [MeSH-minor] Adenoma / complications. Adenoma / pathology. Adenoma / surgery. Child. Diagnosis, Differential. Humans. Magnetic Resonance Imaging. Male. Pituitary Neoplasms / complications. Pituitary Neoplasms / pathology. Pituitary Neoplasms / surgery. Radiosurgery. Treatment Outcome

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  • (PMID = 20662334.001).
  • [ISSN] 0334-018X
  • [Journal-full-title] Journal of pediatric endocrinology & metabolism : JPEM
  • [ISO-abbreviation] J. Pediatr. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] England
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47. Minniti G, Brada M: Radiotherapy and radiosurgery for Cushing's disease. Arq Bras Endocrinol Metabol; 2007 Nov;51(8):1373-80
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  • [Title] Radiotherapy and radiosurgery for Cushing's disease.
  • Patients with residual or recurrent Cushing's disease receive external beam radiotherapy (RT) with the aim of achieving long-term tumour control and normalization of elevated hormone levels.
  • Nevertheless the review of the published literature suggests better hormone and tumour control rates after fractionated irradiation compared to single fraction radiosurgery.
  • On the basis of the available literature, fractionated conventional and stereotactic radiotherapy offer effective treatment for Cushing's disease not controlled with surgery alone.
  • The lower efficacy and higher toxicity of single fraction treatment suggest that SRS is not the appropriate therapy for the majority of patients with Cushing's disease.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma. Adenoma. Pituitary ACTH Hypersecretion. Radiosurgery. Radiotherapy, Conformal

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  • (PMID = 18209876.001).
  • [ISSN] 0004-2730
  • [Journal-full-title] Arquivos brasileiros de endocrinologia e metabologia
  • [ISO-abbreviation] Arq Bras Endocrinol Metabol
  • [Language] eng
  • [Publication-type] Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't; Review
  • [Publication-country] Brazil
  • [Number-of-references] 52
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48. Brown ES, Vazquez M, Nakamura A: Randomized, placebo-controlled, crossover trial of memantine for cognitive changes with corticosteroid therapy. Biol Psychiatry; 2008 Oct 15;64(8):727-9
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  • BACKGROUND: In animal models, corticosteroids are associated with changes in hippocampal structure and functioning that are prevented by glutamate release inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists.
  • Cushing's disease and prescription corticosteroid administration are also associated with memory impairment and hippocampal atrophy.
  • [MeSH-major] Adrenal Cortex Hormones / adverse effects. Cognition Disorders / prevention & control. Excitatory Amino Acid Antagonists / therapeutic use. Memantine / therapeutic use. Nootropic Agents / therapeutic use. Verbal Learning / drug effects

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  • (PMID = 18582848.001).
  • [ISSN] 1873-2402
  • [Journal-full-title] Biological psychiatry
  • [ISO-abbreviation] Biol. Psychiatry
  • [Language] eng
  • [Databank-accession-numbers] ClinicalTrials.gov/ NCT00280774
  • [Publication-type] Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Adrenal Cortex Hormones; 0 / Excitatory Amino Acid Antagonists; 0 / Nootropic Agents; 0 / Receptors, N-Methyl-D-Aspartate; W8O17SJF3T / Memantine
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49. Sonino N, Tomba E, Fava GA: Psychosocial approach to endocrine disease. Adv Psychosom Med; 2007;28:21-33
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  • [Title] Psychosocial approach to endocrine disease.
  • In recent years, there has been growing interest in the psychosocial aspects of endocrine disease, such as the role of life stress in the pathogenesis of some conditions, their association with affective disorders, and the presence of residual symptoms after adequate treatment.
  • In clinical endocrinology, exploration of psychosocial antecedents may elucidate the temporal relationships between life events and symptom onset, as it has been shown to be relevant for pituitary (Cushing's disease, hyperprolactinemia) or thyroid (Graves' disease) conditions, as well as the role of allostatic load, linked to chronic stress, in uncovering a person's vulnerability.
  • After endocrine abnormalities are established, they are frequently associated with a wide range of psychological symptoms: at times, such symptoms reach the level of psychiatric illness (mainly mood and anxiety disorders); at other times, however, they can only be identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR).
  • Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process and induce highly individualized affective responses.
  • The DCPR have been demonstrated to be a valuable tool for psychological assessment in the various phases of endocrine disease from diagnostic to follow-up periods.
  • [MeSH-major] Endocrine System Diseases / diagnosis. Endocrine System Diseases / psychology. Psychophysiologic Disorders / diagnosis
  • [MeSH-minor] Anxiety / diagnosis. Bipolar Disorder / diagnosis. Humans. Irritable Mood. Psychology. Quality of Life / psychology

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  • (PMID = 17684318.001).
  • [ISSN] 0065-3268
  • [Journal-full-title] Advances in psychosomatic medicine
  • [ISO-abbreviation] Adv Psychosom Med
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Switzerland
  • [Number-of-references] 55
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50. Kageyama K, Ikeda H, Nigawara T, Sakihara S, Suda T: Expression of adrenocorticotropic hormone, prolactin and transcriptional factors in clinically nonfunctioning pituitary adenoma. Endocr J; 2007 Dec;54(6):961-8
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  • [Title] Expression of adrenocorticotropic hormone, prolactin and transcriptional factors in clinically nonfunctioning pituitary adenoma.
  • We describe here a case of a clinically nonfunctioning pituitary adenoma, but with expression of ACTH and PRL.
  • A 42-year-old woman was referred to our department for further evaluation of pituitary tumor.
  • GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were all within the normal ranges, while PRL levels were mildly elevated.
  • Both ACTH and cortisol levels were adequately increased in response to CRH, and both were suppressed by a small dose of dexamethasone.
  • Plasma ACTH and cortisol levels were decreased at night, suggesting the circadian rhythms for plasma ACTH levels were undisturbed.
  • Based on these findings we did not clinically suspect ACTH-producing tumor, however immunohistochemistry revealed ACTH immunoreactivity in the pituitary adenoma.
  • Therefore, the tumor was considered a silent corticotroph adenoma.
  • PRL was co-expressed in a significant subpopulation of ACTH-immunoreactive tumor cells.
  • Ptx1, Neuro D1, and T pit were densely expressed and Pit-1 was sparsely expressed in the nuclei of adenoma cells.
  • [MeSH-major] Adenoma, Chromophobe / metabolism. Adrenocorticotropic Hormone / biosynthesis. Pituitary Neoplasms / metabolism. Prolactin / biosynthesis. Transcription Factors / biosynthesis
  • [MeSH-minor] Adult. Basic Helix-Loop-Helix Transcription Factors / metabolism. Female. Homeodomain Proteins / metabolism. Human Growth Hormone / blood. Humans. Immunohistochemistry. T-Box Domain Proteins / metabolism. Thyrotropin / blood. Transcription Factor Pit-1 / metabolism. Vesicular Transport Proteins / metabolism

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  • (PMID = 18079591.001).
  • [ISSN] 1348-4540
  • [Journal-full-title] Endocrine journal
  • [ISO-abbreviation] Endocr. J.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 0 / Basic Helix-Loop-Helix Transcription Factors; 0 / ERGIC2 protein, human; 0 / Homeodomain Proteins; 0 / NEUROD1 protein, human; 0 / T-Box Domain Proteins; 0 / TBX19 protein, human; 0 / Transcription Factor Pit-1; 0 / Transcription Factors; 0 / Vesicular Transport Proteins; 12629-01-5 / Human Growth Hormone; 9002-60-2 / Adrenocorticotropic Hormone; 9002-62-4 / Prolactin; 9002-71-5 / Thyrotropin
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51. Yeh JK, Evans JF, Niu QT, Aloia JF: A possible role for melanocortin peptides in longitudinal growth. J Endocrinol; 2006 Dec;191(3):677-86
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  • Clinical and in vitro data suggest a link between the elevation of the melanocortin peptide, ACTH, and longitudinal growth.
  • Overproduction of ACTH in familial glucocorticoid deficiency (FGD) is associated with increased growth and ACTH increases the differentiation of chondrocytes along the endochondral pathway in vitro.
  • Using the leptin-deficient obese (ob/ob) mouse along with lean control littermates (n = 9-10), we investigated the effects of adrenalectomy (ADX)-induced elevated ACTH with and without peripheral administration of the MC3-R-specific agonist, gamma2-melanocyte stimulating hormone (gamma2-MSH), on longitudinal growth.
  • [MeSH-major] Adrenalectomy. Adrenocorticotropic Hormone / blood. Growth / drug effects. Obesity / blood. gamma-MSH / pharmacology

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  • (PMID = 17170224.001).
  • [ISSN] 0022-0795
  • [Journal-full-title] The Journal of endocrinology
  • [ISO-abbreviation] J. Endocrinol.
  • [Language] eng
  • [Grant] United States / NICHD NIH HHS / HD / R03-HD044692
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Leptin; 0 / gamma-MSH; 9002-60-2 / Adrenocorticotropic Hormone; W980KJ009P / Corticosterone
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52. Güven M, Unay K, Bes C, Poyanli O, Akman B: Hip osteonecrosis in Cushing's disease treated with bone-preserving procedures. J Orthop Sci; 2009 Sep;14(5):662-5
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  • [Title] Hip osteonecrosis in Cushing's disease treated with bone-preserving procedures.
  • [MeSH-major] Bone Transplantation / methods. Femur Head Necrosis / etiology. Femur Head Necrosis / surgery. Pituitary ACTH Hypersecretion / complications

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  • (PMID = 19802682.001).
  • [ISSN] 1436-2023
  • [Journal-full-title] Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association
  • [ISO-abbreviation] J Orthop Sci
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Japan
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53. Schwarte S, Brabant EG, Bastian L, Bruns F: Cortisol as a possible marker of metastatic adrenocortical carcinoma: a case report with 3-year follow-up. Anticancer Res; 2007 Jul-Aug;27(4A):1917-20
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  • [Title] Cortisol as a possible marker of metastatic adrenocortical carcinoma: a case report with 3-year follow-up.
  • BACKGROUND: Adrenocortical carcinoma (ACC) is a rare tumour, sometimes causing glucocorticoid hypersecretion.
  • CASE REPORT: A 55-year-old Caucasian woman presented with adrenal Cushing's disease.
  • Postoperatively, elevated serum cortisol levels normalized.
  • Hypercortisolism occurred again two years later.
  • Initial histological diagnosis was revised according to the increased proliferative changes.
  • Postoperatively, cortisol declined to normal levels.
  • Following curettage and stabilization, radiotherapy of this region with 37.5 Gy was performed, improving slightly elevated cortisol levels and neurological symptoms.
  • In this case of oligometastasizing ACC, serum cortisol values correlated with the clinical course.
  • An aggressive multimodal treatment, including repeated surgical approach with consolidating radiotherapy in cases of incomplete resection, might be indicated to provide symptom control and possible long-term survival in oligometastatic disease of ACC.
  • [MeSH-minor] Adrenalectomy. Antineoplastic Agents / therapeutic use. Bone Neoplasms / radiotherapy. Bone Neoplasms / secondary. Female. Humans. Immunoassay. Liver Neoplasms / drug therapy. Liver Neoplasms / secondary. Middle Aged. Mitotane / therapeutic use. Pituitary ACTH Hypersecretion / etiology

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  • (PMID = 17649795.001).
  • [ISSN] 0250-7005
  • [Journal-full-title] Anticancer research
  • [ISO-abbreviation] Anticancer Res.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Biomarkers, Tumor; 78E4J5IB5J / Mitotane; WI4X0X7BPJ / Hydrocortisone
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54. Teshima T, Hara Y, Takekoshi S, Nezu Y, Harada Y, Yogo T, Teramoto A, Osamura RY, Tagawa M: Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis. Domest Anim Endocrinol; 2009 Jan;36(1):32-44
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  • [Title] Trilostane-induced inhibition of cortisol secretion results in reduced negative feedback at the hypothalamic-pituitary axis.
  • Cushing's disease caused by pituitary corticotroph adenoma in dogs is usually treated by medical treatment, and the efficacy of this treatment has been reported.
  • However, controversy remains as to whether reduced negative feedback through the inhibition of cortisol secretion, similar to Nelson's syndrome, may appear as an adverse effect.
  • The purpose of this study was to investigate the effect of reduced negative feedback through the inhibition of cortisol secretion by daily trilostane administration on the pituitary-adrenal axis in clinically normal dogs.
  • After the initiation of trilostane administration, plasma adrenocorticotropic hormone (ACTH) concentrations were increased remarkably.
  • As assessed by magnetic resonance imaging (MRI) during administration, the pituitary became enlarged.
  • After trilostane administration, the cytoplasmic areas of the pituitary corticotrophs were increased and the ratio of pituitary corticotrophs to all cells in the anterior lobe was greater in the trilostane-treated dogs than that in untreated animals.
  • In addition, histological examinations revealed bilateral adrenal cortical hyperplasia.
  • Using real-time PCR quantification, the expression of proopiomelanocortin (POMC) mRNA in the pituitary and ACTH receptor (ACTH-R) mRNA in the adrenal gland was greater in the dogs treated with trilostane than in untreated dogs.
  • These results indicate that reduced negative feedback induced hyperfunction of the pituitary corticotrophs and pituitary enlargement in healthy dogs.
  • These changes suggest that the inhibition of cortisol secretion by trilostane may increase the risk for accelerating the growth of corticotroph adenomas in dogs with Cushing's disease.
  • [MeSH-major] Antineoplastic Agents / adverse effects. Dihydrotestosterone / analogs & derivatives. Dogs. Hydrocortisone / antagonists & inhibitors. Hypothalamus / drug effects. Pituitary Gland / drug effects
  • [MeSH-minor] Adrenal Glands / chemistry. Adrenal Glands / drug effects. Adrenal Glands / pathology. Adrenocorticotropic Hormone / blood. Animals. Corticotrophs / drug effects. Corticotrophs / ultrastructure. Feedback, Physiological / drug effects. Female. Hyperplasia. Magnetic Resonance Imaging. Male. Pro-Opiomelanocortin / genetics. RNA, Messenger / analysis. Receptors, Corticotropin / genetics

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  • (PMID = 19041802.001).
  • [ISSN] 1879-0054
  • [Journal-full-title] Domestic animal endocrinology
  • [ISO-abbreviation] Domest. Anim. Endocrinol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / RNA, Messenger; 0 / Receptors, Corticotropin; 08J2K08A3Y / Dihydrotestosterone; 66796-54-1 / Pro-Opiomelanocortin; 9002-60-2 / Adrenocorticotropic Hormone; L0FPV48Q5R / trilostane; WI4X0X7BPJ / Hydrocortisone
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55. Pollock BE, Brown PD, Nippoldt TB, Young WF Jr: Pituitary tumor type affects the chance of biochemical remission after radiosurgery of hormone-secreting pituitary adenomas. Neurosurgery; 2008 Jun;62(6):1271-6; discussion 1276-8
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  • [Title] Pituitary tumor type affects the chance of biochemical remission after radiosurgery of hormone-secreting pituitary adenomas.
  • OBJECTIVE: Reported biochemical remission rates have ranged widely after stereotactic radiosurgery for patients with hormone-secreting pituitary adenomas.
  • Confounding variables include histology, radiation dose, use of pituitary-suppressive medications, and length of follow-up.
  • METHODS: A retrospective review of 46 patients with pituitary adenomas (growth hormone-secreting, n = 27; prolactin-secreting, n = 11; adrenocorticotropin-secreting, n = 8) undergoing radiosurgery between January 1990 and December 2003 was conducted.
  • All received a tumor margin dose of 18 Gy or more and were off pituitary-suppressive medications for at least 1 month before radiosurgery.
  • RESULTS: The 4-year remission rates were 87% for patients with Cushing's disease, 67% for patients with acromegaly, and 18% for patients with prolactinomas.
  • Patients with oversecretion of adrenocorticotropin or growth hormone were more likely to achieve remission after radiosurgery than patients with prolactinomas (hazard ratio, 4.4; 95% confidence interval, 1.1-18.2; P = 0.04).
  • Of 44 patients with normal or partial anterior pituitary function before radiosurgery, 16 (36%) developed one or more new anterior pituitary deficits.
  • The incidence of new anterior pituitary deficits was 26% at 4 years.
  • CONCLUSION: There seems to be a differential sensitivity after radiosurgery for hormone-secreting pituitary adenomas.
  • Remission rates are greater for patients with Cushing's disease and acromegaly, whereas radiosurgery is less effective in achieving biochemical remission for patients with prolactinomas.
  • [MeSH-major] Adenoma / metabolism. Adenoma / surgery. Pituitary Hormones / metabolism. Pituitary Neoplasms / metabolism. Pituitary Neoplasms / surgery. Radiosurgery

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  • [CommentIn] Neurosurgery. 2010 May;66(5):E1030; author reply E1030 [20404679.001]
  • (PMID = 18824993.001).
  • [ISSN] 1524-4040
  • [Journal-full-title] Neurosurgery
  • [ISO-abbreviation] Neurosurgery
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Pituitary Hormones
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56. Fracassi F, Mandrioli L, Diana A, Hilbe M, Grinwis G, Gandini G: Pituitary macroadenoma in a cat with diabetes mellitus, hypercortisolism and neurological signs. J Vet Med A Physiol Pathol Clin Med; 2007 Sep;54(7):359-63
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  • [Title] Pituitary macroadenoma in a cat with diabetes mellitus, hypercortisolism and neurological signs.
  • Laboratory investigation revealed diabetes mellitus and pituitary-dependent hypercortisolism.
  • Diagnostic imaging showed bilaterally enlarged adrenals and a large pituitary mass.
  • Histopathological and immunohistochemical examination confirmed the clinical diagnosis of an ACTH-producing pituitary macroadenoma.
  • [MeSH-major] Adrenocorticotropic Hormone / biosynthesis. Cat Diseases / pathology. Cushing Syndrome / veterinary. Pituitary Neoplasms / veterinary

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  • (PMID = 17718809.001).
  • [ISSN] 0931-184X
  • [Journal-full-title] Journal of veterinary medicine. A, Physiology, pathology, clinical medicine
  • [ISO-abbreviation] J Vet Med A Physiol Pathol Clin Med
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
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57. Gross BA, Mindea SA, Pick AJ, Chandler JP, Batjer HH: Diagnostic approach to Cushing disease. Neurosurg Focus; 2007;23(3):E1
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Diagnostic approach to Cushing disease.
  • In Cushing disease, a pituitary corticotroph neoplasm causes secondary adrenal hypercortisolism.
  • An 11 p.m. salivary cortisol level is a modern, simple initial screening tool for the diagnosis of Cushing syndrome.
  • Confirmation with a 24-hour urinary free cortisol test and/or a low-dose dexamethasone suppression test may subsequently be performed.
  • Patients with repeatedly equivocal results should be reevaluated after several months or undergo a corticotropin-releasing hormone (CRH) stimulation test following low-dose dexamethasone suppression to help rule out pseudo-Cushing states.
  • The presence of low morning serum adrenocorticotropic hormone (ACTH) levels then distinguishes primary adrenal hypercortisolism from Cushing disease and the ectopic ACTH syndrome.
  • Patients with moderate ACTH levels can undergo CRH stimulation testing to clarify the underlying disease because those with an ACTH-independent disorder have blunted subsequent ACTH levels.
  • Once ACTH-dependent hypercortisolemia is detected, magnetic resonance (MR) imaging of the pituitary gland can be performed to detect a pituitary neoplasm.
  • Normal or equivocal MR imaging results revealing small pituitary lesions should be followed up with inferior petrosal sinus sampling, a highly specific measure for the diagnosis of Cushing disease in experienced hands.
  • If necessary, body imaging may be used in turn to detect sources of ectopic ACTH.
  • [MeSH-major] Pituitary ACTH Hypersecretion / diagnosis
  • [MeSH-minor] Adrenocorticotropic Hormone / metabolism. Dexamethasone. Humans. Hydrocortisone / metabolism. Pituitary Gland / pathology

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  • (PMID = 17961030.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
  • [Number-of-references] 50
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58. Pecori Giraldi F, Bucciarelli LG, Saccani A, Scacchi M, Pesce S, Losa M, Cavagnini F: Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH-secreting pituitary adenomas in vitro. J Neuroendocrinol; 2007 Mar;19(3):208-12
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  • [Title] Ghrelin stimulates adrenocorticotrophic hormone (ACTH) secretion by human ACTH-secreting pituitary adenomas in vitro.
  • Ghrelin, like its synthetic counterparts, the growth hormone (GH) secretagogues, has been shown to markedly stimulate adrenocorticotrophic hormone (ACTH) and cortisol secretion in humans and the ACTH-releasing effect of GH secretagogues is even greater in patients with pituitary ACTH-secreting tumours.
  • The aim of the present study was to evaluate the effect of ghrelin on ACTH secretion by human pituitary corticotroph tumours in vitro to test the functionality of this circuit.
  • Nine ACTH-secreting pituitary tumours (four microadenomas, five macroadenomas) were collected during surgery and incubated with 10-100 nM human ghrelin or with 10 nM human corticotrophin-releasing hormone (CRH).
  • Control experiments were performed in rat anterior pituitary primary cultures.
  • ACTH secretion was assessed after 4 h and 24 h incubation by immunometric assay.
  • After 4 h of incubation with ghrelin, medium ACTH concentrations were two- to ten-fold higher compared to ACTH concentrations in unstimulated wells.
  • The ACTH-releasing effect of ghrelin was significantly less than the response elicited by 10 nM CRH (up to 40-fold) Similar results were obtained after 24 h of incubation and a superimposable response pattern was observed in rat anterior pituitary primary cultures.
  • The present study demonstrates that the endogenous GH secretagogue, ghrelin, stimulates ACTH secretion directly from human tumoural corticotrophs, as well as from normal rat pituitary, and indicates that the marked ACTH release elicited by ghrelin in patients with Cushing's disease in vivo is due, at least in part, to its action on the pituitary tumour.
  • Moreover, these data uphold the concept of a functional intratumoural ghrelin paracrine circuit in human corticotroph adenomas.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / secretion. Adenoma / secretion. Adrenocorticotropic Hormone / secretion. Corticotrophs / secretion. Peptide Hormones / physiology
  • [MeSH-minor] Adult. Animals. Corticotropin-Releasing Hormone / physiology. Female. Ghrelin. Humans. In Vitro Techniques. Male. Middle Aged. Pituitary ACTH Hypersecretion / metabolism. Pituitary Gland, Anterior / metabolism. Rats

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  • (PMID = 17280594.001).
  • [ISSN] 0953-8194
  • [Journal-full-title] Journal of neuroendocrinology
  • [ISO-abbreviation] J. Neuroendocrinol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Ghrelin; 0 / Peptide Hormones; 9002-60-2 / Adrenocorticotropic Hormone; 9015-71-8 / Corticotropin-Releasing Hormone
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59. Banasiak MJ, Malek AR: Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management. Neurosurg Focus; 2007;23(3):E13
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  • [Title] Nelson syndrome: comprehensive review of pathophysiology, diagnosis, and management.
  • Nelson syndrome (NS) is a rare clinical manifestation of an enlarging pituitary adenoma that can occur following bilateral adrenal gland removal performed for the treatment of Cushing disease.
  • The authors present a comprehensive review of the pathophysiology, diagnosis, and management of NS.
  • [MeSH-major] Nelson Syndrome


60. Sica DA: Endocrine causes of secondary hypertension. J Clin Hypertens (Greenwich); 2008 Jul;10(7):534-40
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  • Various patterns of hypertension exist in the patient with an endocrine source of their disease, including new-onset hypertension in a previously normotensive individual, a loss of blood pressure control in a patient with previously well-controlled blood pressure, and/or labile blood pressure in the setting of either of these 2 patterns.
  • Endocrine forms of secondary hypertension, such as pheochromocytoma and Cushing's disease, are extremely uncommon.
  • Primary aldosteronism can be insidious in its presentation since a supposed hallmark finding, hypokalemia, may be variable in its presentation.
  • [MeSH-major] Endocrine System / physiopathology. Endocrine System Diseases / complications. Endocrine System Diseases / diagnosis. Hypertension / etiology
  • [MeSH-minor] Diagnosis, Differential. Humans. Hyperaldosteronism / complications. Hyperaldosteronism / physiopathology. Pheochromocytoma / complications. Pheochromocytoma / physiopathology. Risk Factors

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  • (PMID = 18607139.001).
  • [ISSN] 1524-6175
  • [Journal-full-title] Journal of clinical hypertension (Greenwich, Conn.)
  • [ISO-abbreviation] J Clin Hypertens (Greenwich)
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 36
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61. Kreutzer J, Jeske I, Hofmann B, Blumcke I, Fahlbusch R, Buchfelder M, Buslei R: No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo. Clin Neuropathol; 2009 Nov-Dec;28(6):430-9
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  • [Title] No effect of the PPAR-gamma agonist rosiglitazone on ACTH or cortisol secretion in Nelson's syndrome and Cushing's disease in vitro and in vivo.
  • OBJECTIVE: Surgical tumor resection remains the primary treatment strategy in ACTH-secreting pituitary adenomas, i.e.
  • Cushing's disease (CD) and Nelson's syndrome (NS).
  • However, an effective long-term pharmacological regime is not available in patients with persistent ACTH-hypersecretion.
  • The nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) is abundantly expressed in most pituitary adenomas.
  • First encouraging data reported that the PPAR-gamma ligand rosiglitazone antagonizes ACTH hypersecretion and exerts also antiproliferative effects in pituitary cell lines.
  • Herein, we studied the potential therapeutical effects of rosiglitazone in patients with ACTH-secreting pituitary adenomas in vitro and in vivo.
  • MATERIALS AND METHODS: Seven patients with persistent ACTH-hypersecretion (3 with NS, 4 with persistent CD) were treated 5 months with rosiglitazone (4 - 16 mg/day).
  • In vitro assays were performed in primary cell cultures obtained from eight additional patients with ACTH-secreting pituitary adenomas applying 80 microM rosiglitazone repeatedly over a time period of 14 days.
  • RESULTS: Our long-term clinical trial with the PPAR-gamma activator rosiglitazone showed no amelioration of clinical symptoms nor an inhibiting effect on ACTH-secretion in vivo.
  • In vitro, rosiglitazone treatment led to a statistically significant decrease of ACTH levels in 2 out of 8 primary cell cultures after 14 days compared to untreated controls.
  • CONCLUSION: In contrast to the initially promising laboratory data gathered in pituitary cell line experiments and nude mice models, our experimental data obtained in primary human ACTH-expressing pituitary adenoma cell cultures as well as our clinical experience with a long-term rosiglitazone trial in approved antidiabetic doses support the recently reported disappointing reports on acute or short-term medical treatment of ACTH-hypersecretion with PPAR-gamma activators.
  • [MeSH-major] Adrenocorticotropic Hormone / secretion. Hydrocortisone / secretion. Nelson Syndrome / blood. PPAR gamma / agonists. Pituitary ACTH Hypersecretion / blood. Thiazolidinediones / pharmacology
  • [MeSH-minor] Adenoma / pathology. Adenoma / secretion. Adult. Female. Humans. In Vitro Techniques. Magnetic Resonance Imaging. Male. Middle Aged. Pituitary Neoplasms / pathology. Pituitary Neoplasms / secretion. Treatment Outcome. Tumor Cells, Cultured

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  • (PMID = 19919817.001).
  • [ISSN] 0722-5091
  • [Journal-full-title] Clinical neuropathology
  • [ISO-abbreviation] Clin. Neuropathol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / PPAR gamma; 0 / Thiazolidinediones; 05V02F2KDG / rosiglitazone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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62. de Bruin C, Feelders RA, Lamberts SW, Hofland LJ: Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome. Rev Endocr Metab Disord; 2009 Jun;10(2):91-102
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  • [Title] Somatostatin and dopamine receptors as targets for medical treatment of Cushing's Syndrome.
  • Somatostatin (SS) and dopamine (DA) receptors are widely expressed in neuroendocrine tumours that cause Cushing's Syndrome (CS).
  • In Cushing's disease, corticotroph adenomas mainly express dopamine receptor subtype 2 (D(2)) and somatostatin receptor subtype 5 (sst(5)), whereas sst(2) is expressed at lower levels.
  • Activation of these receptors can inhibit ACTH-release in primary cultured corticotroph adenomas and compounds that target either sst(5) (pasireotide, or SOM230) or D(2) (cabergoline) have shown significant efficacy in subsets of patients in recent clinical studies.
  • In selected cases of Ectopic ACTH-producing Syndrome (EAS), the sst(2)-preferring compound octreotide is able to reduce cortisol levels effectively.
  • A recent study showed that D(2) receptors are also significantly expressed in the majority of EAS and that cabergoline may decrease cortisol levels in subsets of these patients.
  • [MeSH-major] Cushing Syndrome / drug therapy. Receptors, Dopamine D2 / agonists. Receptors, Somatostatin / agonists
  • [MeSH-minor] ACTH-Secreting Pituitary Adenoma / drug therapy. Adrenocorticotropic Hormone / metabolism. Animals. Antineoplastic Agents / therapeutic use. Humans

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  • (PMID = 18642088.001).
  • [ISSN] 1573-2606
  • [Journal-full-title] Reviews in endocrine & metabolic disorders
  • [ISO-abbreviation] Rev Endocr Metab Disord
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Receptors, Dopamine D2; 0 / Receptors, Somatostatin; 9002-60-2 / Adrenocorticotropic Hormone
  • [Number-of-references] 115
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63. Liu JK, Fleseriu M, Delashaw JB Jr, Ciric IS, Couldwell WT: Treatment options for Cushing disease after unsuccessful transsphenoidal surgery. Neurosurg Focus; 2007;23(3):E8
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  • [Title] Treatment options for Cushing disease after unsuccessful transsphenoidal surgery.
  • Cushing disease is considered an aggressive pituitary endocrinopathy because of the devastating effects from untreated hypercortisolemia.
  • Although they are histologically benign, these adrenocorticotropic hormone (ACTH)-secreting pituitary tumors are associated with significant morbidity and premature death.
  • Currently, transsphenoidal surgery is the primary treatment of Cushing disease associated with an ACTH-secreting pituitary tumor, resulting in remission rates ranging from about 50 to 90%.
  • Some patients, however, will not achieve sustained remission after transsphenoidal surgery and can exhibit persistent or recurrent Cushing disease that requires multimodal treatment to achieve remission.
  • Despite undergoing multiple treatment modalities, some patients may ultimately require bilateral adrenalectomy for definitive treatment to eliminate hypercortisolemia associated with Cushing disease.
  • In this article, the authors review the treatment options for patients who have persistent or recurrent Cushing disease after unsuccessful transsphenoidal surgery.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / surgery. Adenoma / surgery. Pituitary ACTH Hypersecretion / therapy

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  • (PMID = 17961031.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 67
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64. Baldeweg SE, Pollock JR, Powell M, Ahlquist J: A spectrum of behaviour in silent corticotroph pituitary adenomas. Br J Neurosurg; 2005 Feb;19(1):38-42
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  • [Title] A spectrum of behaviour in silent corticotroph pituitary adenomas.
  • Silent corticotroph adenomas (SCA) are pituitary tumours positive on immunohistochemical staining for ACTH but without clinical evidence of Cushing's disease in the patient.
  • Previous reports suggest that these tumours may behave in a more aggressive way then other pituitary adenomas.
  • We identified 22 patients in whom trans-sphenoidal surgery was performed for a non-functioning adenoma (NFA) with positive immunostaining for ACTH between 1990 and 2000 and examined the history of their disease.
  • In four cases hypercortisolaemia was observed later in the course of the disease.
  • We suggest that certain 'silent' corticotroph tumours may have the potential for ACTH secretion leading to hypercortisolaemia at a later stage in the disease.
  • [MeSH-major] Adenoma / physiopathology. Pituitary Neoplasms / physiopathology
  • [MeSH-minor] Adrenocorticotropic Hormone / analysis. Adult. Aged. Anti-Inflammatory Agents / analysis. Female. Humans. Hydrocortisone / analysis. Immunohistochemistry / methods. Magnetic Resonance Imaging / methods. Male. Middle Aged. Neoplasm Recurrence, Local / surgery. Reoperation. Treatment Outcome. Vision Disorders / etiology

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  • (PMID = 16147581.001).
  • [ISSN] 0268-8697
  • [Journal-full-title] British journal of neurosurgery
  • [ISO-abbreviation] Br J Neurosurg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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65. Hook JN, Giordani B, Schteingart DE, Guire K, Giles J, Ryan K, Gebarski SS, Langenecker SA, Starkman MN: Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease. J Int Neuropsychol Soc; 2007 Jan;13(1):21-9
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.
  • Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology.
  • Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment.
  • At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol.
  • Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment.
  • [MeSH-major] Cognition Disorders / diagnosis. Cognition Disorders / epidemiology. Hydrocortisone / metabolism. Pituitary ACTH Hypersecretion

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  • (PMID = 17166300.001).
  • [ISSN] 1355-6177
  • [Journal-full-title] Journal of the International Neuropsychological Society : JINS
  • [ISO-abbreviation] J Int Neuropsychol Soc
  • [Language] eng
  • [Grant] United States / NIDDK NIH HHS / DK / 5R01 DK 51337
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural
  • [Publication-country] England
  • [Chemical-registry-number] WI4X0X7BPJ / Hydrocortisone
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66. Ghadirian AM, Marcovitz S, Pearson Murphy BE: A case of seasonal bipolar disorder exacerbated by Cushing's disease. Compr Psychiatry; 2005 Mar-Apr;46(2):155-8
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  • [Title] A case of seasonal bipolar disorder exacerbated by Cushing's disease.
  • While depression is common in Cushing's syndrome from whatever cause (pituitary, adrenal, or ectopic adrenocorticotropic hormone-secreting tumor or hyperplasia, or exogenous administration of glucocorticoids) and hypercortisolemia is prevalent in major depression, any association between seasonal affective disorder and Cushing's syndrome is unknown.
  • We present a case of seasonal bipolar disorder, gradually worsening for more than 9 years (1985-1994), accompanied by increasing osteoporosis, mild weight gain, and slight truncal obesity in a middle-aged woman.
  • In January 1991, her seasonal affective disorder was successfully treated with light therapy, but in the following year, bipolar mood swings with a seasonal pattern emerged, which were refractory to light therapy and antidepressants but responsive to lithium.
  • In August 1992, she became depressed despite a 1500-mg lithium daily dosage along with light therapy, and, in 1993, a diagnosis of Cushing's disease (Cushing's syndrome as a result of a pituitary adrenocorticotropic hormone-secreting tumor) was made.
  • The pituitary tumor was removed in February 1994, and pituitary function was fully restored by 1996.
  • While the symptoms of Cushing's syndrome subsided, her bipolar illness continued to require maintenance treatment with low doses of lithium but did not require light therapy.
  • [MeSH-major] Adrenocorticotropic Hormone / secretion. Bipolar Disorder / diagnosis. Cushing Syndrome / complications. Seasonal Affective Disorder / diagnosis
  • [MeSH-minor] Adrenalectomy. Antidepressive Agents / therapeutic use. Antimanic Agents / therapeutic use. Combined Modality Therapy. Diagnosis, Differential. Female. Follow-Up Studies. Humans. Lithium Carbonate / therapeutic use. Middle Aged. Petrosal Sinus Sampling. Phototherapy. Pituitary Neoplasms / complications. Pituitary Neoplasms / diagnosis. Pituitary Neoplasms / psychology. Pituitary Neoplasms / secretion. Treatment Failure


67. Raverot G, Wierinckx A, Jouanneau E, Auger C, Borson-Chazot F, Lachuer J, Pugeat M, Trouillas J: Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing's disease. Eur J Endocrinol; 2010 Jul;163(1):35-43
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  • [Title] Clinical, hormonal and molecular characterization of pituitary ACTH adenomas without (silent corticotroph adenomas) and with Cushing's disease.
  • OBJECTIVE: Silent corticotroph adenomas (SCAs) are rare pituitary tumours immunoreactive for ACTH, but without clinical evidence of Cushing's disease.
  • We characterized SCAs based on clinical, hormonal and molecular data, and compared the characteristics of these tumours with those of macro (MCA)- and micro (mCA)-ACTH adenomas with Cushing's disease.
  • METHODS: Fifty ACTH adenomas (14 SCAs, 15 MCAs and 21 mCAs) with complete corresponding clinical, radiological and biochemical data were selected.
  • Histological corticotroph differentiation; immunostaining for ACTH, beta-endorphin and beta-LPH; and mRNA expression levels of TPIT, POMC, GRalpha, prohormone convertase 1/3 (PC1/3) and galectin-3 were compared in 21 representative tumours.
  • RESULTS: Despite the absence of clinical hypercortisolism in patients with SCA, elevated plasma ACTH levels that were similar to those associated with mCA were observed.
  • The cortisol/ACTH ratio was similar between SCA and MCA groups and lower than that found with mCA (P<0.05).
  • After an i.v. dexamethasone suppression test, ACTH levels were significantly higher in patients with MCA than in those with mCA (P<0.05).
  • CONCLUSIONS: Despite the absence of hypercortisolism, SCAs exhibit histological, biochemical and molecular corticotroph differentiation.

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  • (PMID = 20385723.001).
  • [ISSN] 1479-683X
  • [Journal-full-title] European journal of endocrinology
  • [ISO-abbreviation] Eur. J. Endocrinol.
  • [Language] ENG
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Galectin 3; 0 / Homeodomain Proteins; 0 / Receptors, Glucocorticoid; 0 / T-Box Domain Proteins; 0 / TBX19 protein, human; 0 / glucocorticoid receptor alpha; 66796-54-1 / Pro-Opiomelanocortin; 9002-60-2 / Adrenocorticotropic Hormone; EC 3.4.21.93 / Proprotein Convertase 1; WI4X0X7BPJ / Hydrocortisone
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68. Axlund TW, Behrend EN, Sorjonen DC, Simpson ST, Kemppainen RJ: Canine hypophysectomy using a ventral paramedian approach. Vet Surg; 2005 May-Jun;34(3):179-89
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  • OBJECTIVE: To evaluate the degree of pituitary exposure, completeness of hypophysectomy, and perioperative morbidity associated with an alternative paramedian surgical approach and excisional technique for the canine pituitary gland.
  • METHODS: Surgical landmarks for the pituitary were determined by computed tomography (CT), and then using a ventral paramedian approach medial to the rami of the mandible, the pituitary was exposed and removed en bloc by manipulation and ultrasonic aspiration.
  • Statistically significant decreases in secretion of all measured pituitary hormones except adrenocorticotropic hormone (ACTH) occurred after hypophysectomy.
  • Despite the absence of gross evidence of residual pituitary tissue, immunohistochemical staining revealed residual pituitary cells in the sella turcica of most dogs.
  • CONCLUSION: CT imaging and a paramedian approach facilitated surgical access to the pituitary gland by a transoral technique; however, use of an ultrasonic aspirator removed all visible pituitary glands but left cellular remnants capable of ACTH secretion in the sella turcica.
  • CLINICAL RELEVANCE: Although this technique did not result in complete hypophysectomy, clinical use in dogs with pituitary-dependent hyperadrenocorticism is warranted because the goal is not complete hypophysectomy but removal of a pituitary tumor.
  • [MeSH-major] Adrenocortical Hyperfunction / veterinary. Dog Diseases / surgery. Hypophysectomy / veterinary. Pituitary Gland / surgery
  • [MeSH-minor] Animals. Dogs. Pituitary Function Tests / veterinary. Tomography, X-Ray Computed

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  • (PMID = 16115073.001).
  • [ISSN] 0161-3499
  • [Journal-full-title] Veterinary surgery : VS
  • [ISO-abbreviation] Vet Surg
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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69. Dhatariya K: DHEA levels in treated Cushing's disease may contribute to low quality of life. Clin Endocrinol (Oxf); 2005 Feb;62(2):258-9
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  • [Title] DHEA levels in treated Cushing's disease may contribute to low quality of life.
  • [MeSH-major] Cushing Syndrome / blood. Dehydroepiandrosterone / blood. Quality of Life

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  • [CommentOn] Clin Endocrinol (Oxf). 2004 Oct;61(4):458-65 [15473878.001]
  • (PMID = 15670205.001).
  • [ISSN] 0300-0664
  • [Journal-full-title] Clinical endocrinology
  • [ISO-abbreviation] Clin. Endocrinol. (Oxf)
  • [Language] eng
  • [Publication-type] Comment; Letter
  • [Publication-country] England
  • [Chemical-registry-number] 459AG36T1B / Dehydroepiandrosterone
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70. Andrioli M, Pecori Giraldi F, De Martin M, Cattaneo A, Carzaniga C, Cavagnini F: Differential diagnosis of ACTH-dependent hypercortisolism: imaging versus laboratory. Pituitary; 2009;12(4):294-6
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Differential diagnosis of ACTH-dependent hypercortisolism: imaging versus laboratory.
  • Differential diagnosis of ACTH-dependent Cushing's syndrome often presents major difficulties.
  • Diagnostic troubles are increased by suboptimal specificity of endocrine tests, the rarity of ectopic ACTH secretion and the frequent incidental discovery of pituitary adenomas.
  • A 43-year-old female reported with mild signs and symptoms of hypercortisolism, and initial hormonal tests and results of pituitary imaging (7-mm adenoma) were suggestive for Cushing's disease.
  • However, inadequate response to corticotrophin-releasing hormone and failure to suppress after 8 mg dexamethasone pointed towards an ectopic source.
  • Inferior petrosal sinus sampling revealed an absent center:periphery ACTH gradient but octreoscan and (18)F-FDG-PET-CT failed to detect abnormal tracer accumulation.
  • Pathology identified a typical, ACTH-staining carcinoid and the diagnosis was confirmed by postsurgical hypoadrenalism.
  • In conclusion, imaging may prove unsatisfactory or even misleading for the etiologial diagnosis of ACTH-dependent Cushing's syndrome and should therefore be interpreted only in context with results of hormonal dynamic testing.
  • [MeSH-major] Adrenocorticotropic Hormone / metabolism. Cushing Syndrome / diagnosis. Cushing Syndrome / metabolism

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  • [Cites] J Clin Endocrinol Metab. 2004 May;89(5):2214-21 [15126544.001]
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  • (PMID = 19294516.001).
  • [ISSN] 1573-7403
  • [Journal-full-title] Pituitary
  • [ISO-abbreviation] Pituitary
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
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71. Brown CG, Graves TK: Hyperadrenocorticism: treating dogs. Compend Contin Educ Vet; 2007 Mar;29(3):132-4, 136, 138 passim; quiz 144-5
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  • [Title] Hyperadrenocorticism: treating dogs.
  • This article is a complete review of all reported therapies for hyperadrenocorticism in dogs.
  • Both medical and surgical options for treating pituitary-dependent hyperadrenocorticism and adrenal tumor-related disease are discussed, and the efficacy, safety, and use of these treatments are compared.
  • [MeSH-major] Adrenalectomy / veterinary. Adrenocortical Hyperfunction / veterinary. Dog Diseases / drug therapy. Dog Diseases / surgery

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  • (PMID = 17726933.001).
  • [ISSN] 1940-8307
  • [Journal-full-title] Compendium (Yardley, PA)
  • [ISO-abbreviation] Compend Contin Educ Vet
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 08J2K08A3Y / Dihydrotestosterone; 78E4J5IB5J / Mitotane; L0FPV48Q5R / trilostane; R9400W927I / Ketoconazole
  • [Number-of-references] 53
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72. Albiero C, Juarez-Allen L, Longobardi V, Danilowicz K, Manavela MP, Bruno OD: [Analysis of a pituitary adenoma registry]. Medicina (B Aires); 2010;70(5):415-20
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Analysis of a pituitary adenoma registry].
  • [Transliterated title] Análisis de un Registro de adenomas pituitarios.
  • Collection and analysis of data obtained during the clinical treatment of pituitary tumours are of great utility in the decision making process, when facing clinical situations.
  • We report here data on 519 from 670 patients with pituitary adenomas obtained from a computerized registry.
  • Final diagnosis was acromegaly in 176, Cushing's disease in 153, prolactinoma in 101 and clinically non-functioning adenoma in 89.
  • Mean age at diagnosis was 43.9 ± 13.5 (16-80) for acromegalics, 35.7 ± 12.9 (14-72) for Cushing's, 30.0 ± 13.4 (15-79) for prolactinoma and 52.1 ± 15.2 (17-79), for non-functioning tumours.
  • The setup of an institutional registry on pituitary tumours constitutes a useful tool to analyze clinical experience, optimize the cost/benefit ratio of procedures used for diagnosis and to ameliorate therapeutic strategies, improving patient's care.
  • [MeSH-major] Adenoma. Pituitary Neoplasms. Prolactinoma

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  • (PMID = 20920957.001).
  • [ISSN] 0025-7680
  • [Journal-full-title] Medicina
  • [ISO-abbreviation] Medicina (B Aires)
  • [Language] spa
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] Argentina
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73. Barber TM, Adams E, Ansorge O, Byrne JV, Karavitaki N, Wass JA: Nelson's syndrome. Eur J Endocrinol; 2010 Oct;163(4):495-507
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  • [Title] Nelson's syndrome.
  • Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease.
  • In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre.
  • Definitive diagnostic criteria for Nelson's syndrome are lacking.
  • We argue in favour of a new set of criteria.
  • We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images;.
  • ii) an elevated 0800 h plasma level of ACTH (>500 ng/l) in addition to progressive elevations of ACTH (a rise of >30%) on at least three consecutive occasions.
  • Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA.
  • Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours.

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  • (PMID = 20668020.001).
  • [ISSN] 1479-683X
  • [Journal-full-title] European journal of endocrinology
  • [ISO-abbreviation] Eur. J. Endocrinol.
  • [Language] ENG
  • [Publication-type] Journal Article; Review
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Alkylating Agents; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide; 9002-60-2 / Adrenocorticotropic Hormone
  • [Number-of-references] 101
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74. Kells J, Dollbaum CM: Saliva tests, part 1: clinical use, elements of testing, and guidelines for posttreatment interpretation. Int J Pharm Compd; 2009 Jul-Aug;13(4):280-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • The baseline measurement of hormone levels in saliva provides an accurate assessment and can be used to identify or monitor a number of clinical conditions, including climacteric changes in perimenopausal or postmenopausal women, adrenal disorders such as Addison's disease or Cushing's disease, and androgen deficiency in men and women, the age-related decrease of hormones such as testosterone and dehydroepiandrosterone can also be assessed and monitored.
  • In this first of a two-part series, we discuss the clinical use and basic elements of saliva testing and provide guidelines for postreatment interpretation by compounding pharmacists.

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  • (PMID = 23966517.001).
  • [ISSN] 1092-4221
  • [Journal-full-title] International journal of pharmaceutical compounding
  • [ISO-abbreviation] Int J Pharm Compd
  • [Language] ENG
  • [Publication-type] Journal Article
  • [Publication-country] United States
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75. Jagannathan J, Sheehan JP, Jane JA Jr: Evaluation and management of Cushing syndrome in cases of negative sellar magnetic resonance imaging. Neurosurg Focus; 2007;23(3):E3
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Evaluation and management of Cushing syndrome in cases of negative sellar magnetic resonance imaging.
  • The treatment of patients with Cushing disease and without magnetic resonance (MR) imaging evidence of Cushing disease (that is, negative MR imaging) is discussed in this paper.
  • Magnetic resonance imaging is the diagnostic modality of choice in Cushing disease, but in up to 40% of these patients negative imaging can be caused by tumor-related factors and limitations in imaging techniques.
  • In cases in which the MR imaging is negative, it is critical to make sure that the diagnosis of Cushing disease is correct.
  • If these evaluations suggest a pituitary source of the hypercortisolemia, then transsphenoidal surgery remains the treatment of choice.
  • Radiosurgery is an effective treatment option in patients with persistent Cushing disease.
  • [MeSH-major] Pituitary ACTH Hypersecretion / pathology. Pituitary ACTH Hypersecretion / therapy
  • [MeSH-minor] Adrenocorticotropic Hormone / metabolism. False Negative Reactions. Humans. Magnetic Resonance Imaging. Neurosurgical Procedures

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  • (PMID = 17961018.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
  • [Number-of-references] 47
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76. Guignat L, Assie G, Bertagna X, Bertherat J: [Corticotroph adenoma]. Presse Med; 2009 Jan;38(1):125-32
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Corticotroph adenoma].
  • Corticotroph adenomas cause ACTH oversecretion responsible for Cushing's disease.
  • This represents the most frequent cause of Cushing's syndrome, or chronic excess of endogenous glucocorticoids.
  • Cushing's disease diagnosis requires careful hormonal and imaging investigations, aiming first at the diagnosis of Cushing's syndrome and in a second step at the diagnosis of its pituitary origin.
  • The treatment of corticotroph adenoma is mainly based on pituitary surgery.
  • In case of failure of pituitary surgery, or in patients in whom surgery is not appropriate as a first line treatment, medical therapy (mainly anticortisolic drugs), pituitary radiotherapy or surgical bilateral adrenalectomy can be discussed.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / complications. Pituitary ACTH Hypersecretion / etiology. Pituitary Neoplasms / complications
  • [MeSH-minor] Adrenalectomy. Adrenocorticotropic Hormone / analysis. Chemotherapy, Adjuvant. Corticotropin-Releasing Hormone / analysis. Cushing Syndrome / diagnosis. Cushing Syndrome / etiology. Cushing Syndrome / therapy. Diagnosis, Differential. Humans. Hydrocortisone / analysis. Hydrocortisone / antagonists & inhibitors. Magnetic Resonance Imaging. Neoadjuvant Therapy. Radiotherapy, Adjuvant

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  • (PMID = 19041214.001).
  • [ISSN] 2213-0276
  • [Journal-full-title] Presse medicale (Paris, France : 1983)
  • [ISO-abbreviation] Presse Med
  • [Language] fre
  • [Publication-type] English Abstract; Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone; 9015-71-8 / Corticotropin-Releasing Hormone; WI4X0X7BPJ / Hydrocortisone
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77. Biller BM, Sheppard M: The Network for the Enhancement of Endocrinology and Oncology Knowledge: a case-based consideration of current practice in Cushing's disease and acromegaly. Best Pract Res Clin Endocrinol Metab; 2009 Dec;23 Suppl 1:S1-4
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The Network for the Enhancement of Endocrinology and Oncology Knowledge: a case-based consideration of current practice in Cushing's disease and acromegaly.
  • [MeSH-major] Acromegaly / therapy. Endocrinology / methods. Medical Oncology / methods. Pituitary ACTH Hypersecretion / therapy. Societies, Scientific

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  • (PMID = 20129189.001).
  • [ISSN] 1878-1594
  • [Journal-full-title] Best practice & research. Clinical endocrinology & metabolism
  • [ISO-abbreviation] Best Pract. Res. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Introductory Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
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78. Oki Y: [Treatment of pituitary Cushing's syndrome in internal medicine]. Nihon Naika Gakkai Zasshi; 2006 Apr 10;95(4):683-8
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] [Treatment of pituitary Cushing's syndrome in internal medicine].
  • [MeSH-major] Cushing Syndrome / drug therapy

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  • (PMID = 16722437.001).
  • [ISSN] 0021-5384
  • [Journal-full-title] Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine
  • [ISO-abbreviation] Nippon Naika Gakkai Zasshi
  • [Language] jpn
  • [Publication-type] Journal Article; Review
  • [Publication-country] Japan
  • [Number-of-references] 5
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79. Raitila A, Georgitsi M, Karhu A, Tuppurainen K, Mäkinen MJ, Birkenkamp-Demtröder K, Salmenkivi K, Orntoft TF, Arola J, Launonen V, Vahteristo P, Aaltonen LA: No evidence of somatic aryl hydrocarbon receptor interacting protein mutations in sporadic endocrine neoplasia. Endocr Relat Cancer; 2007 Sep;14(3):901-6
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  • Germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene were recently observed in patients with pituitary adenoma predisposition (PAP).
  • Though AIP mutation-positive individuals with prolactin-, mixed growth hormone/prolactin-, and ACTH-producing pituitary adenomas as well as non-secreting pituitary adenomas have been reported, most mutation-positive patients have had growth hormone-producing adenomas diagnosed at relatively young age.
  • Pituitary adenomas are also component tumors of some familial endocrine neoplasia syndromes such as multiple endocrine neoplasia type 1 (MEN1) and Carney complex (CNC).
  • Genes underlying MEN1 and CNC are rarely mutated in sporadic pituitary adenomas, but more often in other lesions contributing to these two syndromes.
  • Thus far, the occurrence of somatic AIP mutations has not been studied in endocrine tumors other than pituitary adenomas.
  • Here, we have analyzed 32 pituitary adenomas and 79 other tumors of the endocrine system for somatic AIP mutations by direct sequencing.
  • However, two out of nine patients with prolactin-producing adenoma were shown to harbor a Finnish founder mutation (Q14X) with a complete loss of the wild-type allele in the tumors.
  • These results are in agreement with previous studies in that prolactin-producing adenomas are component tumors in PAP.
  • The data also support the previous finding that somatic AIP mutations are not common in pituitary adenomas and suggest that such mutations are rare in other endocrine tumors as well.
  • [MeSH-major] Adenoma / genetics. Carcinoma / genetics. Endocrine Gland Neoplasms / genetics. Mutation. Proteins / genetics

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  • (PMID = 17914118.001).
  • [ISSN] 1351-0088
  • [Journal-full-title] Endocrine-related cancer
  • [ISO-abbreviation] Endocr. Relat. Cancer
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Intracellular Signaling Peptides and Proteins; 0 / Proteins; 0 / aryl hydrocarbon receptor-interacting protein
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80. Triay J, Lambert AP: Cushing's disease occurring in preganacy. Diabet Med; 2010 Jan;27(1):123-5
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  • [Title] Cushing's disease occurring in preganacy.
  • [MeSH-major] Hydrocortisone / metabolism. Pituitary ACTH Hypersecretion / diagnosis. Pre-Eclampsia / surgery

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  • (PMID = 20121900.001).
  • [ISSN] 1464-5491
  • [Journal-full-title] Diabetic medicine : a journal of the British Diabetic Association
  • [ISO-abbreviation] Diabet. Med.
  • [Language] eng
  • [Publication-type] Case Reports; Letter
  • [Publication-country] England
  • [Chemical-registry-number] WI4X0X7BPJ / Hydrocortisone
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81. Karavitaki N, Thanabalasingham G, Shore HC, Trifanescu R, Ansorge O, Meston N, Turner HE, Wass JA: Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma. Clin Endocrinol (Oxf); 2006 Oct;65(4):524-9
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  • [Title] Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.
  • BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy.
  • OBJECTIVE: We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas.
  • PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied.
  • RESULTS: Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas).
  • CONCLUSIONS: Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas.
  • Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice.
  • [MeSH-major] Adenoma / blood. Biomarkers, Tumor / blood. Pituitary Neoplasms / blood. Prolactin / blood. Prolactinoma / blood
  • [MeSH-minor] Adolescent. Adult. Aged. Aged, 80 and over. Diagnosis, Differential. Female. Humans. Immunohistochemistry / methods. Male. Middle Aged. Reference Values. Statistics, Nonparametric

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  • (PMID = 16984247.001).
  • [ISSN] 0300-0664
  • [Journal-full-title] Clinical endocrinology
  • [ISO-abbreviation] Clin. Endocrinol. (Oxf)
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 9002-62-4 / Prolactin
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82. Hwang YC, Chung JH, Min YK, Lee MS, Lee MK, Kim KW: Comparisons between macroadenomas and microadenomas in Cushing's disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci; 2009 Feb;24(1):46-51
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  • [Title] Comparisons between macroadenomas and microadenomas in Cushing's disease: characteristics of hormone secretion and clinical outcomes.
  • It has been suggested that the patients with Cushing's disease secondary to pituitary macroadenomas (>10 mm) have higher basal adrenocorticotropic hormone (ACTH) levels, which are less suppressible on high-dose dexamethasone suppression tests (HDDST).
  • Basal morning plasma ACTH levels were 101.5+/-23.2 pg/mL for macroadenoma patients and 83.6+/-11.1 pg/mL for microadenoma patients (mean+/-SEMs) (p=0.44).
  • Morning serum cortisol levels were 26.8+/-3.2 microg/dL for macroadenoma patients and 29.5+/-2.9 microg/dL for microadenoma patients (p=0.77).
  • Thus, tumor size is not a major determinant of hormone secretion or clinical outcomes in patients with Cushing's disease.
  • [MeSH-major] Adenoma / metabolism. Adrenocorticotropic Hormone / secretion. Hydrocortisone / secretion. Pituitary ACTH Hypersecretion / diagnosis. Pituitary Neoplasms / metabolism

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  • (PMID = 19270812.001).
  • [ISSN] 1598-6357
  • [Journal-full-title] Journal of Korean medical science
  • [ISO-abbreviation] J. Korean Med. Sci.
  • [Language] eng
  • [Publication-type] Comparative Study; Journal Article
  • [Publication-country] Korea (South)
  • [Chemical-registry-number] 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
  • [Other-IDs] NLM/ PMC2650989
  • [Keywords] NOTNLM ; Outcome Assessment (Health Care) / Pituitary ACTH Hypersecretion / Pituitary Adenoma
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83. Tsuchiya K, Ohta K, Yoshimoto T, Doi M, Izumiyama H, Hirata Y: A Case of acromegaly associated with subclinical Cushing's disease. Endocr J; 2006 Oct;53(5):679-85
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  • [Title] A Case of acromegaly associated with subclinical Cushing's disease.
  • Magnetic resonance imaging of the brain revealed the presence of a pituitary macroadenoma.
  • Endocrine examination of the hypothalamo-pituitary-adrenal (HPA) axis showed a lack of circadian rhythm of ACTH and cortisol, non-suppressibility to low-dose (1 mg), but suppressibility to high-dose (8 mg) dexamethasone, and normal response to CRH stimulation.
  • The tumor resected by transsphenoidal surgery was histopathologically consistent with the diagnosis of eosinophilic adenoma: positive immunoreactivities of GH, PRL and ACTH were demonstrated, but negative immunoreactivities of prohormone convertase (PC) 1/3 by immunohistochemical method.
  • Metabolic co-morbidities such as diabetes and hypertension disappeared after removal of the pituitary tumor.
  • This is a very rare case of GH-producing pituitary adenoma causing typical acromegaly with concomitant production of ACTH causing subclinical Cushing's disease.
  • [MeSH-major] Acromegaly / complications. Pituitary ACTH Hypersecretion / complications
  • [MeSH-minor] Adenoma / diagnosis. Adenoma / radiography. Adenoma / surgery. Adrenocorticotropic Hormone / blood. Diabetes Mellitus, Type 2 / blood. Diabetes Mellitus, Type 2 / complications. Growth Hormone-Secreting Pituitary Adenoma / diagnosis. Growth Hormone-Secreting Pituitary Adenoma / radiography. Growth Hormone-Secreting Pituitary Adenoma / surgery. Human Growth Hormone / blood. Humans. Hydrocortisone / blood. Male. Middle Aged. Pituitary Function Tests

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  • (PMID = 16926523.001).
  • [ISSN] 0918-8959
  • [Journal-full-title] Endocrine journal
  • [ISO-abbreviation] Endocr. J.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Japan
  • [Chemical-registry-number] 12629-01-5 / Human Growth Hormone; 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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84. Dalvi AN, Thapar PM, Vijay Kumar K, Kamble RS, Rege SA, Deshpande AA, Shah NS, Menon PS: Laparoscopic adrenalectomy: Gaining experience by graded approach. J Minim Access Surg; 2006 Jun;2(2):59-66
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  • INTRODUCTION: Laparoscopic adrenalectomy (LA) has become a gold standard in management of most of the adrenal disorders.
  • Though report on the first laparoscopic adrenalectomy dates back to 1992, there is no series of LA reported from India.
  • Starting Feb 2001, a graded approach to LA was undertaken in our center.
  • Patients were divided into Group A - unilateral LA and Group B - bilateral LA (BLA).
  • The indications in Group A were pheochromocytoma (n=7), Conn's syndrome (n=3), Cushing's adenoma (n=2), incidentaloma (n=2); and in Group B, Cushing's disease (CD) following failed trans-sphenoid pituitary surgery (n = 8); ectopic ACTH- producing Cushing's syndrome (n=1) and congenital adrenal hyperplasia (CAH) (n=1).
  • Three patients in Group B developed Nelson's syndrome.
  • CONCLUSION: LA though technically demanding, is feasible and safe.
  • Graded approach to LA is the key to success.

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  • (PMID = 21170236.001).
  • [ISSN] 0972-9941
  • [Journal-full-title] Journal of minimal access surgery
  • [ISO-abbreviation] J Minim Access Surg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] India
  • [Other-IDs] NLM/ PMC2997274
  • [Keywords] NOTNLM ; Laparoscopic adrenalectomy / graded approach
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85. Kasperlik-Załuska AA, Bonicki W, Jeske W, Janik J, Zgliczyński W, Czernicki Z: Nelson's syndrome -- 46 years later: clinical experience with 37 patients. Zentralbl Neurochir; 2006 Feb;67(1):14-20
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  • [Title] Nelson's syndrome -- 46 years later: clinical experience with 37 patients.
  • OBJECTIVE: Pituitary tumours occurring after bilateral adrenalectomy for Cushing's disease (Nelson's syndrome) are frequently aggressive, so an early diagnosis and careful management are of prime importance.
  • For a new insight into this entity it is necessary to analyse the factors predisposing to its development and the course of the disease, as well as the methods of diagnosis and modalities of treatment.
  • PATIENTS AND METHODS: Thirty-seven patients with Nelson's syndrome were observed, 32 women and 5 men, aged 16 to 61 years at the time of pituitary tumour detection (at present, 27 to 82 years old).
  • The diagnostic methods included clinical observation, imaging examinations (X-ray studies, CT, MRI), hormonal evaluation (especially ACTH and cortisol levels during replacement therapy) and ophthalmologic investigations.
  • RESULTS: The clinical analysis indicated that young age at the time of adrenalectomy, pregnancy, insufficient replacement therapy and fulminant course of Cushing's disease were the main factors predisposing to Nelson's syndrome.
  • Plasma ACTH levels varied between 32.6 pmol/l in an early phase to 2 000 pmol/l in the full-blown syndrome.
  • CONCLUSIONS: MRI, ophthalmologic examination and plasma ACTH determination were the most valuable investigations for early diagnosis of Nelson's syndrome.
  • [MeSH-major] Nelson Syndrome / surgery. Pituitary Neoplasms / surgery
  • [MeSH-minor] Adolescent. Adrenalectomy / adverse effects. Adrenocorticotropic Hormone / blood. Adult. Aged. Aged, 80 and over. Cushing Syndrome / complications. Cushing Syndrome / surgery. Eye Diseases / diagnosis. Eye Diseases / etiology. Female. Follow-Up Studies. Hormone Replacement Therapy. Humans. Hydrocortisone / blood. Magnetic Resonance Imaging. Male. Middle Aged. Neurosurgical Procedures. Tomography, X-Ray Computed

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  • (PMID = 16518746.001).
  • [ISSN] 0044-4251
  • [Journal-full-title] Zentralblatt für Neurochirurgie
  • [ISO-abbreviation] Zentralbl. Neurochir.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Germany
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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86. Ishtiaq O, Haq MU, Rizwan A, Masood MQ, Mehar S, Jabbar A: Etiology, functional status and short term outcome of patients with pituitary lesions. An experience from a developing country. J Pak Med Assoc; 2009 Dec;59(12):839-43
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  • [Title] Etiology, functional status and short term outcome of patients with pituitary lesions. An experience from a developing country.
  • OBJECTIVE: To describe the etiology, functional status and short term outcome of patients with pituitary lesions (PL).
  • METHODS: Brain or pituitary MRI reports of 3753 patients were analyzed for PL over the period of 2000 to 2007, done at the Aga Khan University Hospital (AKUH), Karachi, Pakistan.
  • MRIs with reported PL and all those ordered by Endocrinologists with or without pituitary abnormalities, were included in the analysis.
  • PL were defined as pituitary tumors, cysts, haemorrhage, hypoplasia; and empty sella.
  • RESULTS: In the analysis of 338 MRI reports, 23% had normal pituitary gland on MRI examination.
  • Hypogonadotrophic hypogonadism was the commonest (38.5%) endocrine abnormality seen with normal pituitary MRI, followed by hypopituitarism (5.1%).
  • Patients with microadenoma included 39.5% prolactinomas, 18.6% cushing disease, 14% acromegaly, 4.7% hypogonadotrophic hypogonadism and 2.3% hypopituitrism.
  • [MeSH-major] Pituitary Neoplasms / epidemiology
  • [MeSH-minor] Adenoma / epidemiology. Adolescent. Adult. Aged. Child. Empty Sella Syndrome / epidemiology. Humans. Male. Middle Aged. Pakistan / epidemiology. Prolactinoma / epidemiology. Young Adult

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  • (PMID = 20201177.001).
  • [ISSN] 0030-9982
  • [Journal-full-title] JPMA. The Journal of the Pakistan Medical Association
  • [ISO-abbreviation] J Pak Med Assoc
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Pakistan
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87. Gnjidić Z, Sajko T, Kudelić N, Malenica M, Vizner B, Vrkljan M, Hat J, Rumboldt Z: Reversible "brain atrophy" in patients with Cushing's disease. Coll Antropol; 2008 Dec;32(4):1165-70
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  • [Title] Reversible "brain atrophy" in patients with Cushing's disease.
  • During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing's disease.
  • This "brain atrophy" appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level.
  • Observed difference between degree of "brain atrophy" in the Cushing's disease group and in the control group was statistically significant (p < 0.001).
  • The degree of "brain atrophy" correlated well with the duration of Cushing's disease.
  • Partial reversibility of "brain atrophy" was noticed during the 2nd, 3rd and 4th year after surgery and normalization of cortisol level.
  • Increased cortisol level is one of the causative factors in pathogenesis of "brain atrophy".
  • Loss of brain volume is at least partially reversible after normalization of cortisol levels.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / pathology. Adenoma / pathology. Brain / pathology. Pituitary ACTH Hypersecretion / pathology

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  • (PMID = 19149224.001).
  • [ISSN] 0350-6134
  • [Journal-full-title] Collegium antropologicum
  • [ISO-abbreviation] Coll Antropol
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Croatia
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88. Sacerdote A, Weiss K, Tran T, Rokeya Noor B, McFarlane SI: Hypertension in patients with Cushing's disease: pathophysiology, diagnosis, and management. Curr Hypertens Rep; 2005 Jun;7(3):212-8
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  • [Title] Hypertension in patients with Cushing's disease: pathophysiology, diagnosis, and management.
  • Hypertension is a very common comorbidity in patients with Cushing's disease/syndrome, resulting from the interplay of several pathophysiologic mechanisms, including stimulation of mineralocorticoid and glucocorticoid receptors as well as the associated insulin resistance, sleep apnea, and overexpression of renin-angiotensin system.
  • Although treatment of Cushing's disease results in resolution or amelioration of hypertension in these patients, a significant proportion of patients do not achieve complete cure or require a prolonged period of time for complete response to therapy.
  • Therefore, therapeutic strategies for Cushing's-specific hypertension are necessary to decrease morbidity and mortality associated with this disease.
  • In this review, we discuss the pathophysiology of hypertension in patients with Cushing's disease, highlighting the therapeutic options, including the exciting new developments in the role of peroxisome proliferator-activated receptor (PPAR)-g agonists in the management of this patient population.
  • [MeSH-major] Cushing Syndrome / physiopathology. Cushing Syndrome / therapy. Hypertension / physiopathology. Hypertension / therapy

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  • (PMID = 15913497.001).
  • [ISSN] 1522-6417
  • [Journal-full-title] Current hypertension reports
  • [ISO-abbreviation] Curr. Hypertens. Rep.
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Number-of-references] 46
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89. Singer E, Strohm S, Göbel U, Bieringer M, Schmidt D, Schneider W, Kettritz R, Luft FC: Cushing's disease, hypertension, and other sequels. Hypertension; 2008 Dec;52(6):1001-5
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  • [Title] Cushing's disease, hypertension, and other sequels.
  • [MeSH-major] Hypertension / complications. Hypertension / diagnosis. Pituitary ACTH Hypersecretion / complications. Pituitary ACTH Hypersecretion / diagnosis. Suicide
  • [MeSH-minor] Fatal Outcome. Humans. Male. Mental Disorders / complications. Mental Disorders / diagnosis. Mental Disorders / physiopathology. Middle Aged

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  • (PMID = 18981320.001).
  • [ISSN] 1524-4563
  • [Journal-full-title] Hypertension (Dallas, Tex. : 1979)
  • [ISO-abbreviation] Hypertension
  • [Language] eng
  • [Publication-type] Case Reports; Clinical Conference; Journal Article
  • [Publication-country] United States
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90. Liao CC, Lin SY, Lin HW, Chen KH, Chang LH, Chen ST, Wang J: Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma mimicking polycystic ovary syndrome. Taiwan J Obstet Gynecol; 2006 Jun;45(2):176-9
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  • [Title] Menstrual abnormalities in a woman with ACTH-dependent pituitary macroadenoma mimicking polycystic ovary syndrome.
  • OBJECTIVE: Here, we present a case of ACTH-dependent pituitary macroadenoma (Cushing's disease) resulting in secondary amenorrhea mimicking polycystic ovary syndrome (PCOS).
  • She visited a gynecologic clinic where PCOS was impressed according to the clinical manifestation and ultrasound finding.
  • Endocrine studies revealed: serum prolactin 21 ng/mL (3.0-20 ng/mL), FSH 5.69 mIU/mL (3.4-10.0 mIU/mL), LH 1.01 mIU/mL (1.1-11.6 mIU/mL), E2 < 20 pg/mL (follicular phase 53-258 pg/mL), ACTH 110 pg/mL (0-46.0 pg/mL), cortisol 26.7 microg/dL at 8 a.m. (5.0-25 microg/dL), cortisol 21.3 microg/dL at 11 p.m. (half of normal morning value).
  • Right pituitary macroadenoma was diagnosed through a series of dexamethasone tests and MRI.
  • CONCLUSION: PCOS is a common disease resulting in secondary amenorrhea.
  • However, Cushing's syndrome resulting from pituitary macroadenoma should also be considered.
  • Therefore, a careful history, observation, physical examination, and endocrine studies can differentiate between patients with PCOS and Cushing's disease.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / complications. ACTH-Secreting Pituitary Adenoma / diagnosis. Amenorrhea / etiology. Pituitary Neoplasms / complications. Pituitary Neoplasms / diagnosis. Polycystic Ovary Syndrome / diagnosis
  • [MeSH-minor] Adult. Craniotomy. Diagnosis, Differential. Female. Humans. Magnetic Resonance Imaging

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  • (PMID = 17197364.001).
  • [ISSN] 1875-6263
  • [Journal-full-title] Taiwanese journal of obstetrics & gynecology
  • [ISO-abbreviation] Taiwan J Obstet Gynecol
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] China
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91. John M, Lila AR, Bandgar T, Menon PS, Shah NS: Diagnostic efficacy of midnight cortisol and midnight ACTH in the diagnosis and localisation of Cushing's syndrome. Pituitary; 2010;13(1):48-53
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  • [Title] Diagnostic efficacy of midnight cortisol and midnight ACTH in the diagnosis and localisation of Cushing's syndrome.
  • Classical tests for diagnosis of Cushing's syndrome (CS) like urine free cortisol and dexamethasone suppression tests have limitations in various clinical settings.
  • This study evaluated the usefulness of sleeping midnight serum cortisol (SMNC) as a diagnostic test for hypercortisolemia.
  • A simultaneously done midnight plasma ACTH level was used to classify the disease as ACTH dependent or independent.
  • Standard biochemical tests, SMNC, midnight plasma ACTH and appropriate imaging evaluated patients with a clinical suspicion of Cushing's syndrome.
  • We evaluated 43 patients with CS comprising of 34 patients with Cushing's disease (CD), 2 patients with thymic carcinoid producing ectopic CS, 5 patients with adrenal carcinoma and 2 with adrenal adenoma.
  • SMNC, midnight plasma ACTH and dexamethasone suppressed cortisol was collected from patients with a suspicion of CS.
  • SMNC achieved 100% sensitivity in the diagnosis of endogenous CS at cut offs of 138 nmol/l and below.
  • At a cut off of 1.65 pmol/l, midnight plasma ACTH could distinguish ACTH independent causes of CS with 100% sensitivity.
  • We concluded that a single midnight collection could identify all patients with CS and classify the ACTH status at the proposed cut offs.
  • [MeSH-major] Adrenocorticotropic Hormone / blood. Cushing Syndrome / diagnosis. Hydrocortisone / blood
  • [MeSH-minor] Adolescent. Adult. Child. Diagnosis. Female. Histocytochemistry / standards. Humans. Male. Middle Aged. Sensitivity and Specificity. Sleep. Young Adult

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  • (PMID = 19714471.001).
  • [ISSN] 1573-7403
  • [Journal-full-title] Pituitary
  • [ISO-abbreviation] Pituitary
  • [Language] eng
  • [Publication-type] Evaluation Studies; Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone; WI4X0X7BPJ / Hydrocortisone
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92. Pecori Giraldi F, Pesce S, Maroni P, Pagliardini L, Lasio G, Losa M, Cavagnini F: Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours. J Neuroendocrinol; 2010 Apr;22(4):294-300
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  • [Title] Inhibitory effect of prepro-thyrotrophin-releasing hormone (178-199) on adrenocorticotrophic hormone secretion by human corticotroph tumours.
  • Prepro-thyrotrophin-releasing hormone (TRH) (178-199), a 22-amino acid cleavage product of the TRH prohormone, has been postulated to act as an adrenocorticotrophin hormone (ACTH)-release inhibitor.
  • Indeed, although in vitro evidence indicates that this peptide may inhibit basal and stimulated ACTH secretion in rodent anterior pituitary primary cultures and cell lines, not all studies concur and no study has as yet evaluated the effect of this peptide in Cushing's disease.
  • Twenty-four human ACTH-secreting pituitary tumours (13 macroadenomas, 11 microadenomas) were collected during surgery and incubated with 10 or 100 nm preproTRH(178-199).
  • ACTH secretion was assessed after 4 and 24 h of incubation by immunometric assay and expressed relative to levels observed in control, unchallenged wells (= 100%).
  • Parallel experiments were performed in rat anterior pituitary primary cultures.
  • A clear inhibition of ACTH secretion at 4 and 24 h was observed in 12 specimens (for 10 nm ppTRH: 70 +/- 4% control at 4 h and 83 +/- 5% control at 24 h; for 100 nm ppTRH: 70 +/- 4% control at 4 h and 85 +/- 5% control at 24 h), whereas a mild and short-lasting stimulatory effect was observed in three tumours and no changes in ACTH secretion in the remaining nine tumoural specimens.
  • Significant inhibition of ACTH secretion by preproTRH(178-199) in rat pituitary cultures was observed after 24 h of incubation.
  • The present study conducted in a large series of human corticotroph tumours shows that preproTRH(178-199) inhibits tumoural ACTH secretion in a sizable proportion of specimens, in close relation to the size of the tumour and its sensitivity to glucocorticoid negative feedback.
  • This appears a promising avenue of research and further studies are warranted to explore the full scope of preproTRH(178-199) as a regulator of ACTH secretion.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / secretion. Adenoma / secretion. Adrenocorticotropic Hormone / secretion. Peptide Fragments / pharmacology. Protein Precursors / pharmacology. Thyrotropin-Releasing Hormone / pharmacology
  • [MeSH-minor] Animals. Cell Culture Techniques. Cells, Cultured. Corticotropin-Releasing Hormone / pharmacology. Dexamethasone / pharmacology. Dose-Response Relationship, Drug. Down-Regulation / drug effects. Drug Evaluation, Preclinical. Female. Hormone Antagonists / pharmacology. Humans. Male. Pituitary Gland, Anterior / drug effects. Pituitary Gland, Anterior / metabolism. Rats

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  • (PMID = 20136686.001).
  • [ISSN] 1365-2826
  • [Journal-full-title] Journal of neuroendocrinology
  • [ISO-abbreviation] J. Neuroendocrinol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Hormone Antagonists; 0 / Peptide Fragments; 0 / Protein Precursors; 122018-92-2 / prepro-thyrotropin-releasing hormone (178-199); 5Y5F15120W / Thyrotropin-Releasing Hormone; 7S5I7G3JQL / Dexamethasone; 9002-60-2 / Adrenocorticotropic Hormone; 9015-71-8 / Corticotropin-Releasing Hormone
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93. Takata MC, Kebebew E, Clark OH, Duh QY: Laparoscopic bilateral adrenalectomy: results for 30 consecutive cases. Surg Endosc; 2008 Jan;22(1):202-7
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  • BACKGROUND: Most patients requiring bilateral adrenalectomy have adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome.
  • Some of these patients are severely debilitated from the chronic effects of cortisol overproduction.
  • The patient records were analyzed to obtain patient demographics, disease etiology, surgical approach, operating room information, postoperative complications (30 days), hospital length of stay (LOS), and follow-up information.
  • The indications for bilateral adrenalectomy were refractory Cushing's disease (n = 16), occult ectopic ACTH syndrome (n = 9), and bilateral pheochromocytoma (n = 5).
  • At this writing, the patients with Cushing's syndrome available for follow-up evaluation continue to receive steroid replacement, and all the pheochromocytoma patients have experienced a documented postoperative biochemical cure.
  • [MeSH-minor] Adolescent. Adult. Cohort Studies. Cushing Syndrome / diagnosis. Cushing Syndrome / mortality. Cushing Syndrome / surgery. Female. Follow-Up Studies. Humans. Male. Middle Aged. Minimally Invasive Surgical Procedures / methods. Pheochromocytoma / diagnosis. Pheochromocytoma / mortality. Pheochromocytoma / surgery. Retrospective Studies. Risk Assessment. Survival Rate. Time Factors. Treatment Outcome

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  • (PMID = 17623238.001).
  • [ISSN] 1432-2218
  • [Journal-full-title] Surgical endoscopy
  • [ISO-abbreviation] Surg Endosc
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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94. Catrina SB, Virtanen K, Hällsten K, Lönnqvist F, Nuutila P, Brismar K: Effect of rosiglitazone on early-morning plasma cortisol levels. Neuro Endocrinol Lett; 2005 Dec;26(6):763-4; author reply 765
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  • [Title] Effect of rosiglitazone on early-morning plasma cortisol levels.
  • OBJECTIVES: PPAR-gamma agonists are able to inhibit pituitary tumour development and tumoral hormonal secretion in rodents both in vitro and in vivo.
  • Their use for treatment of Cushing Disease (CD) has been suggested but the clinical experience with the two PPAR-gamma agonists commercially available (rosiglitazone and pioglitazone) was not impressive.
  • We report here the effect on early-morning plasma cortisol levels of a long-time treatment with rosiglitazone at the highest approved dose.
  • METHODS: Because PPAR-gamma receptors are located in normal corticotroph cells we tested in a placebo-controlled study the influence of rosiglitazone on cortisol secretion.
  • Plasma morning cortisol (8.00 a.m.) was measured at the baseline and at the end of the study.
  • RESULTS: Rosiglitazone vs placebo did not modify the early morning plasma levels of cortisol (13 microg/dl [3-21] vs 11 microg/dl [7-23] [median and range]) after 26 weeks of treatment.
  • CONCLUSION: The discrepancy between in vitro and animal data on one side and clinical data on the other side warrant further investigations into the mechanisms of action of PPAR-gamma agonists on ACTH secretion before other clinical studies will be conducted.
  • [MeSH-minor] Double-Blind Method. Humans. Hypoglycemic Agents / pharmacology. Hypothalamo-Hypophyseal System / drug effects. Pituitary-Adrenal System / drug effects

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  • [CommentOn] Neuro Endocrinol Lett. 2005 Feb;26(1):51-4 [15726020.001]
  • (PMID = 16380670.001).
  • [ISSN] 0172-780X
  • [Journal-full-title] Neuro endocrinology letters
  • [ISO-abbreviation] Neuro Endocrinol. Lett.
  • [Language] eng
  • [Publication-type] Comment; Letter; Randomized Controlled Trial
  • [Publication-country] Sweden
  • [Chemical-registry-number] 0 / Hypoglycemic Agents; 0 / PPAR gamma; 0 / Thiazolidinediones; 05V02F2KDG / rosiglitazone; WI4X0X7BPJ / Hydrocortisone
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95. Bangaru ML, Woodliff J, Raff H, Kansra S: Growth suppression of mouse pituitary corticotroph tumor AtT20 cells by curcumin: a model for treating Cushing's disease. PLoS One; 2010;5(4):e9893
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  • [Title] Growth suppression of mouse pituitary corticotroph tumor AtT20 cells by curcumin: a model for treating Cushing's disease.
  • BACKGROUND: Pituitary corticotroph tumors secrete excess adrenocorticotrophic hormone (ACTH) resulting in Cushing's disease (CD).
  • Our laboratory recently demonstrated that curcumin inhibited growth and induced apoptosis in prolactin- and growth hormone-producing tumor cells.
  • Subsequently, Schaaf et.al. confirmed our findings and also showed the in vivo effectiveness of curcumin to suppress pituitary tumorigenesis.
  • Finally, curcumin had a concentration-dependent suppressive effect on ACTH secretion from AtT20 cells.
  • CONCLUSION: The ability of curcumin to inhibit NFkappaB and induce apoptosis in pituitary corticotroph tumor cells leads us to propose developing it as a novel therapeutic agent for the treatment of CD.
  • [MeSH-major] ACTH-Secreting Pituitary Adenoma / drug therapy. Cell Proliferation / drug effects. Curcumin / pharmacology. Pituitary ACTH Hypersecretion / drug therapy
  • [MeSH-minor] Adrenocorticotropic Hormone / secretion. Animals. Antineoplastic Agents. Apoptosis / drug effects. Cell Line, Tumor. Dose-Response Relationship, Drug. Mice. NF-kappa B / antagonists & inhibitors

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  • [ErratumIn] PLoS One. 2010;5(4). doi:10.1371/annotation/38a101d6-a1f2-4a74-ab63-bc5c61e5f62b
  • (PMID = 20405005.001).
  • [ISSN] 1932-6203
  • [Journal-full-title] PloS one
  • [ISO-abbreviation] PLoS ONE
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / NF-kappa B; 9002-60-2 / Adrenocorticotropic Hormone; IT942ZTH98 / Curcumin
  • [Other-IDs] NLM/ PMC2854133
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96. Cereseto M, Reinés A, Ferrero A, Sifonios L, Rubio M, Wikinski S: Chronic treatment with high doses of corticosterone decreases cytoskeletal proteins in the rat hippocampus. Eur J Neurosci; 2006 Dec;24(12):3354-64
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  • Hypercortisolism is a common trait of Cushing's disease and depression.
  • These two disorders also share hippocampal volume decrease and cognitive deficits.
  • However, experimentally induced hypercortisolism induces neuronal atrophy, which has been proposed to be the phenomenon underlying the hippocampal shrinkage.
  • These results provide a subcellular insight into the trophic changes found in experimental models of hypercortisolism.
  • The coincidence between decrements in MAP2 and glutamate release suggests possible links between high glucocorticoid levels, dendritic atrophy and the cognitive impairment reported in patients suffering from Cushing's disease and depression.

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  • (PMID = 17229084.001).
  • [ISSN] 0953-816X
  • [Journal-full-title] The European journal of neuroscience
  • [ISO-abbreviation] Eur. J. Neurosci.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] France
  • [Chemical-registry-number] 0 / Anti-Inflammatory Agents; 0 / Cytoskeletal Proteins; 3KX376GY7L / Glutamic Acid; EC 4.2.1.11 / Phosphopyruvate Hydratase; W980KJ009P / Corticosterone
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97. Lindsay JR, Nansel T, Baid S, Gumowski J, Nieman LK: Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission. J Clin Endocrinol Metab; 2006 Feb;91(2):447-53
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Long-term impaired quality of life in Cushing's syndrome despite initial improvement after surgical remission.
  • CONTEXT: Cushing's syndrome (CS) is associated with symptoms that may impair health-related quality of life (HRQL).
  • METHODS: We used the short-form 36 survey to evaluate HRQL in 23 patients with Cushing's disease before and after transsphenoidal surgery (age, 42.7 +/- 12.0 yr; 19 women and four men) and in a cross-section of 343 CS patients (age, 48.2 +/- 14.1 yr; 265 women and 78 men) in remission for up to 25.8 yr after surgery (adrenal, 5%; ectopic, 6%).
  • RESULTS: Active Cushing's disease was associated with low PCS and MCS scores (P < 0.05).
  • Logistic regression demonstrated that previous pituitary radiation and current glucocorticoid use had little effect on HRQL outcomes.
  • Determination of modifiable factors that contribute to impaired HRQL may help reduce the physical and psychosocial burden of this disease.
  • [MeSH-major] Cushing Syndrome / psychology. Cushing Syndrome / surgery

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  • [CommentIn] Nat Clin Pract Endocrinol Metab. 2006 Dec;2(12):666-7 [17143312.001]
  • (PMID = 16278266.001).
  • [ISSN] 0021-972X
  • [Journal-full-title] The Journal of clinical endocrinology and metabolism
  • [ISO-abbreviation] J. Clin. Endocrinol. Metab.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
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98. Lad SP, Patil CG, Laws ER Jr, Katznelson L: The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing's disease. Neurosurg Focus; 2007;23(3):E2
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] The role of inferior petrosal sinus sampling in the diagnostic localization of Cushing's disease.
  • Cushing's syndrome can present a complex problem of differential diagnosis.
  • Of cases in which hypercortisolemia results from an adrenocorticotropic hormone (ACTH)-dependent process, approximately 80% are due to a pituitary adenoma (Cushing's disease [CD]), 10% are due to adrenal lesions, and the remaining 10% are secondary to ectopic ACTH secretion.
  • For patients with CD, surgical removal of the pituitary adenoma is the treatment of choice.
  • Thus, localization of the source of ACTH secretion is critical in guiding timely treatment decisions.
  • Inferior petrosal sinus sampling (IPSS) is considered to be the gold standard for confirming the origin of ACTH secretion in patients with Cushing's syndrome.
  • A number of other techniques are discussed including sampling from the cavernous sinus, the jugular vein, and multiple sites to aid the diagnosis and lateralization of ACTH-producing pituitary adenomas.
  • [MeSH-major] Petrosal Sinus Sampling / methods. Pituitary ACTH Hypersecretion / diagnosis
  • [MeSH-minor] Adrenocorticotropic Hormone / metabolism. Humans. Predictive Value of Tests

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  • (PMID = 17961020.001).
  • [ISSN] 1092-0684
  • [Journal-full-title] Neurosurgical focus
  • [ISO-abbreviation] Neurosurg Focus
  • [Language] eng
  • [Publication-type] Journal Article; Review
  • [Publication-country] United States
  • [Chemical-registry-number] 9002-60-2 / Adrenocorticotropic Hormone
  • [Number-of-references] 46
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99. Mori A, Lee P, Izawa T, Oda H, Mizutani H, Koyama H, Arai T, Sako T: Assessing the immune state of dogs suffering from pituitary gland dependent hyperadrenocorticism by determining changes in peripheral lymphocyte subsets. Vet Res Commun; 2009 Oct;33(7):757-69
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Assessing the immune state of dogs suffering from pituitary gland dependent hyperadrenocorticism by determining changes in peripheral lymphocyte subsets.
  • In order to evaluate the immune state of dogs suffering from pituitary-dependent hyperadrenocorticism (PDH), peripheral lymphocyte subsets were examined.
  • Twenty seven PDH dogs were categorized into 4 groups based on their post serum cortisol concentrations by ACTH stimulation test: 2-5, excellent control (n = 8); 5-20, fair control (n = 7); >20, poor control (n = 4); and untreated (n = 8).
  • Furthermore, lymphocyte subset distribution in excellent control PDH dogs without concurrent disease (n = 4) better resembled that of control dogs as compared to PDH dogs with concurrent disease (n = 4).
  • Furthermore, treatment of both PDH and concurrent disease might improve lymphocyte subset distribution.
  • [MeSH-major] Adrenocortical Hyperfunction / veterinary. Dog Diseases / immunology. Dogs / immunology. Lymphocyte Subsets / immunology
  • [MeSH-minor] Animals. Anti-Bacterial Agents / therapeutic use. B-Lymphocytes / immunology. Female. Humans. Informed Consent. Leukocyte Count. Male. Pituitary Gland / pathology. Polyuria / immunology. Polyuria / veterinary. Reference Values. T-Lymphocytes / immunology. T-Lymphocytes, Cytotoxic / immunology. T-Lymphocytes, Helper-Inducer / immunology

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  • (PMID = 19462252.001).
  • [ISSN] 1573-7446
  • [Journal-full-title] Veterinary research communications
  • [ISO-abbreviation] Vet. Res. Commun.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] Netherlands
  • [Chemical-registry-number] 0 / Anti-Bacterial Agents
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100. Adams JR, Blevins LS Jr, Allen GS, Verity DK, Devin JK: Disorders of water metabolism following transsphenoidal pituitary surgery: a single institution's experience. Pituitary; 2006;9(2):93-9