Cushing Syndrome results from effects of supraphysiologic glucocorticoid levels originating from either exogenous administration or endogenous overproduction by the adrenal gland (adrenocorticotropic hormone [ACTH]-dependent) or by abnormal adrenocortical tissues (ACTH-independent).
ACTH-dependent Cushing syndrome (80% of all Cushing syndrome cases) is usually caused by overproduction of ACTH by the pituitary gland, causing adrenal hyperplasia. Pituitary adenomas account for ~85% of these cases (Cushing disease). Ectopic ACTH-secreting tumors and nonneoplastic corticotropin hypersecretion cause the remaining 20% of ACTH-dependent cases.
Ectopic ACTH syndrome refers to excessive ACTH production resulting from an endocrine or nonendocrine tumor, usually of the pancreas, thyroid, or lung (eg, small-cell lung cancer).
ACTH-independent Cushing syndrome is usually caused by adrenal adenomas and carcinomas.
CLINICAL PRESENTATION
The most common findings in Cushing syndrome are central obesity and facial rounding (90% of patients). Peripheral obesity and fat accumulation occur in 50% of patients. Fat accumulation in the dorsocervical area (buffalo hump) is nonspecific, but increased supraclavicular fat pads are more specific for Cushing syndrome. Patients are often described as having moon facies and a buffalo hump.
Other findings may include myopathy or muscular weakness, abdominal striae, hypertension, glucose intolerance, psychiatric changes, gonadal dysfunction, and amenorrhea and hirsutism in women.
Up to 60% of patients develop Cushing-induced osteoporosis; ~40% present with back pain, and 20% progress to spinal compression fractures.
DIAGNOSIS
Hypercortisolism can be established with a 24-hour urinary free cortisol (UFC), midnight plasma cortisol, late-night (11 pm) salivary cortisol, and/or low-dose dexamethasone suppression test (DST).
Other tests to determine etiology are plasma ACTH test; adrenal vein catheterization; metyrapone stimulation test; adrenal, chest, or abdominal computed tomography (CT); corticotropin-releasing hormone (CRH) stimulation test; inferior petrosal sinus sampling; and pituitary magnetic resonance imaging (MRI).
Adrenal nodules and masses are identified using high-resolution CT scanning or MRI.
