A Diagnostic Approach to Cushingʼs Syndrome

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Abstract
Cushing's syndrome is caused by either chronic excessive effects of endogenous cortisol or exogenous glucocorticoid administration. Patients with Cushingoid obesity mimic those with Cushing's syndrome. Tests have been developed to assess the functional status of the hypothalamic-pituitary-adrenal axis. In a patient, an elevated urinary free cortisol excretion rate or plasma cortisol to a low-dose dexamethasone (Dex) suppression test (DST) has a diagnostic accuracy for endogenous Cushing's syndrome of >90%. Plasma ACTH assists in differentiating patients with ACTH-dependent Cushing's syndrome (pituitary and ectopic ACTH-secreting tumors) from those with ACTH-independent Cushing's syndrome (adrenal tumors or adenomatous hyperplasia). The high-dose overnight (4-8 mg at 11 to 12 p.m.) and multiple-dose DSTs have sensitivities of 89 and 69%, respectively, and specificities of 100% for diagnosing Cushing's disease. Patients with adrenal causes never have false-positive responses to a high-dose DST, but rarely a false-positive response occurs in those with ectopic ACTH-secreting tumors. About 20% of patients with Cushing's disease have false-negative high-dose DST responses. A positive cortisol response to corticotropin-releasing hormone administration or a positive high-dose DST has a specificity for diagnosis of Cushing's disease approaching 100%. An approach to evaluating surreptitious glucocorticoid users or those taking drugs that accelerate Dex clearance is reviewed. Testing includes measuring both plasma endogenous and synthetic corticosteroids. (C) Lippincott-Raven Publishers.

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