Ectopic Non-Hypothalamic Tumor CRH Secretion Causes Hyperplasia/Hypersecretion by the Pituitary Corticotrophs, Resulting in Pituitary Hypersecretion of ACTH (and Subsequent, Bilateral Adrenal Hyperplasia and Cortisol Hypersecretion)
In Some Patients, Pituitary ACTH Secretion Can Be Inhibited by Dexamethasone (NEJM, 1984) [MEDLINE]
However, Many of These Tumors Also Secrete ACTH, Which is Not Suppressed by Dexamethasone (Clin Endocrinol, 1986) [MEDLINE] (J Clin Endocrinol Metab, 1986) [MEDLINE] (J Endocrinol, 1987) [MEDLINE] (Clin Endocrinol-Oxf, 1992) [MEDLINE] (Endocr Rev, 1992) [MEDLINE]
Iatrogenic/Factitious Cushing Syndrome Due to Administration of Exogenous ACTH (Not Glucocorticoids)
Epidemiology
Rare (Accounts for <1% of All Cushing Syndrome Cases)
ACTH-Independent Cushing Syndrome (20% of All Cushing Syndrome Cases)
This Disorder Must Be Distinguished from Macronodular Hyperplasia in Cushing Disease in Which Plasma ACTH Concentrations are Not Suppressed (Endocr Rev, 2001) [MEDLINE]
Iatrogenic/Factitious Cushing Syndrome
Epidemiology
Iatrogenic/Factitious Cushing Syndrome (Due to Exogenous Glucocorticoid Intake) is a Rare Etiology of Cushing Syndrome (Accounting for <1% of All Cushing Syndrome Cases) (J Clin Endocrinol Metab, 1996) [MEDLINE] (Arch Intern Med, 1998) [MEDLINE]
Often Occurs in Patients With Access to These Medications Via the Health Profession
Iatrogenic/Factitious Cushing Syndrome (Due to Exogenous Glucocorticoid Intake) is the Most Common Etiology of ACTH-Independent Cushing Syndrome
The Clearance of Some Inhaled Steroids May Be Delayed by Ritonavir, Resulting in Cushing Syndrome (see xxxx)) (J Clin Endocrinol Metab, 2005) [MEDLINE]
Both of These are Progestins with Some Intrinsic Glucocorticoid Activity
Physiology
Iatrogenic/Factitious Cushing Syndrome is Most Commonly Due to Administration of Excessive Amounts of a Synthetic Glucocorticoid (Arch Intern Med, 1998) [MEDLINE]
Plasma ACTH, Serum/Salivary Cortisol Levels, and Urinary Cortisol Excretion, Unless Hydrocortisone (i.e. Cortisol] is the Steroid Administered) are All Low (Arch Intern Med, 1998) [MEDLINE]
Biochemical Hypercortisolism without Cushingoid Features
Epidemiology
Case Reports
Physiology
Impaired Cortisone-to-Cortisol Conversion In Vivo and Decreased Cortisol-to-Cortisone Metabolites, Consistent with Impaired 11-β-Hydroxysteroid Dehydrogenase Type 1 Activity
Increased Cortisol Clearance was Suggested as the Mechanism by Which the Patients were Protected from Tissue Actions of Cortisol
Chronic hypercortisolism inhibits both hypothalamic corticotropin-releasing hormone (CRH) and vasopressin secretion as well as ACTH secretion by normal pituitary corticotrophs (J Clin Endocrinol Metab, 1991) [MEDLINE]
Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary gland to suppress the secretion of adrenocorticotropic hormone (ACTH)
Specifically, dexamethasone binds to glucocorticoid receptors in the anterior pituitary gland, which lie outside the blood–brain barrier, resulting in regulatory modulation
Cushing’s syndrome secondary to ectopic cortisol production by an ovarian carcinoma. J Clin Endocrinol Metab. 1983;57(4):737 [MEDLINE]
Ectopic secretion of corticotropin-releasing factor as a cause of Cushing’s syndrome. A clinical, morphologic, and biochemical study. N Engl J Med. 1984;311(1):13 [MEDLINE]
ACTH and CRF-producing bronchial carcinoid associated with Cushing’s syndrome. Clin Endocrinol. 1986;24:523 [MEDLINE]
Cushing’s syndrome from the therapeutic use of intramuscular dexamethasone acetate. Arch Intern Med. 1986;146(9):1848 [MEDLINE]
A phaeochromocytoma presenting with Cushing’s syndrome associated with increased concentrations of circulating corticotrophin-releasing factor. J Endocrinol. 1987;113(1):133 [MEDLINE]
Cushing’s syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma. Clin Endocrinol (Oxf). 1992;37(5):460 [MEDLINE]
Corticotropin-releasing hormone in humans. Endocr Rev. 1992;13(2):164 [MEDLINE]
Iatrogenic Cushing’s syndrome due to nasal betamethasone: a problem not to be sniffed at! Postgrad Med J. 1995;71(834):231 [MEDLINE]
Glucocorticoidlike activity of megestrol. A summary of Food and Drug Administration experience and a review of the literature. Arch Intern Med. 1997;157(15):1651 [MEDLINE]
Cushing’s syndrome attributable to topical use of lotrisone. Endocr Pract. 1997;3(3):140 [MEDLINE]
Cushing syndrome due to surreptitious glucocorticoid administration. Arch Intern Med. 1998;158(3):294 [MEDLINE]
Ectopic and abnormal hormone receptors in adrenal Cushing’s syndrome. Endocr Rev. 2001;22(1):75 [MEDLINE]
Iatrogenic Cushing’s syndrome with osteoporosis and secondary adrenal failure in human immunodeficiency virus-infected patients receiving inhaled corticosteroids and ritonavir-boosted protease inhibitors: six cases. J Clin Endocrinol Metab. 2005;90(7):4394 [MEDLINE]
A woman with Cushing’s syndrome after use of an Indonesian herb: a case report. Neth J Med. 2007;65(4):150 [MEDLINE]
Complications of chronic use of skin lightening cosmetics. Int J Dermatol. 2008;47(4):344 [MEDLINE]
Physiology
Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing’s disease and major depression: potential clinical implications. J Clin Endocrinol Metab. 1991;72(2):260 [MEDLINE]
