The patient in this scenario has symptoms of Cushing’s syndrome. In the setting of high baseline ACTH, suppression of cortisol with a high dose of dexamethasone indicates pituitary adenoma as the cause of disease.
The most common cause of Cushing’s syndrome is the administration of exogenous steroids (iatrogenic Cushing’s). Several endogenous processes can also produce Cushing’s syndrome, including pituitary adenoma (Cushing’s disease, 70% of endogenous cases), adrenal adenoma (15% of case), and ectopic ACTH production (15% of cases). To distinguish between a pituitary adenoma that produces ACTH and an ectopic carcinoma producing ACTH, a dexamethasone suppression test is completed.
Kirk et al. reviews the diagnosis and clinical manifestations of Cushing’s syndrome. ACTH levels and the dexamethasone suppression test are used to distinguish between different endogenous Cushing’s etiologies. Dexamethasone is administered overnight and serum cortisol is checked in the morning. In the setting of high ACTH levels, high-dose dexamethasone suppression will decrease cortisol levels in a pituitary adenoma (via suppression of ACTH release), while cortisol suppression will not occur in the case of ectopic ACTH production from a carcinoma.
Bertagna et al. reviews the diagnosis of Cushing’s disease using imaging and the dexamethasone suppression test. Diagnosis of Cushing's syndrome requires that chronic hypercortisolism is demonstrated biologically, with 24-hour urinary cortisol, late-evening plasma or salivary cortisol, or midnight 1-mg or the 48-h-low-dose dexamethasone suppression test. A high dose dexamethasone suppression test may then follow.
Illustration A shows diagrams the classic features of Cushing's syndrome.
Image A shows the hypothalamic-pituitary-adrenal axis (HPA axis). The HPA axis demonstrates negative feedback to regulate cortisol production via cortisol suppressing CRH from the hypothalamus and ACTH from the pituitary gland.
Answer 1: Cortisol suppression after dexamethasone administration amid normal baseline ACTH levels is a normal finding in patients without Cushing’s syndrome.
Answer 3: A lack of cortisol suppression after dexamethasone administration amid high baseline ACTH levels indicates an ectopic ACTH-producing tumor. Examples include small cell lung cancer and bronchial carcinoids.
Answer 4: A lack of cortisol suppression after dexamethasone administration amid low baseline ACTH levels is diagnostic of a cortisol-producing tumor, such as an adrenal adenoma.
Answer 5: Dexamethasone administration does not increase serum cortisol above pre-test values.
Kirk LF Jr, Hash RB, Katner HP, Jones T. Cushing's disease: clinical manifestations and diagnostic evaluation. Am Fam Physician. 2000 Sep 1;62(5):1119-27, 1133-4. Review. Erratum in: Am Fam Physician 2002 Feb 1;65(3):386
PMID:10997535 (Link to Abstract)
Bertagna X, Guignat L, Groussin L, Bertherat J. Cushing's disease. Best Pract Res Clin Endocrinol Metab. 2009 Oct;23(5):607-23. Review
PMID:19945026 (Link to Abstract)
USMLE World Step 1 QBank Question #927. Copyright © USMLEWorld, LLC 2012