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Cushing's Syndrome


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Cushing's Syndrome

Cushing's syndrome (the clinical effects of increased glucocorticoid hormone) is most often iatrogenic, due to therapy with glucocorticoid drugs. ACTH-secreting pituitary microadenomas (Cushing's disease) account for 80% of cases of endogenous Cushing's syndrome. Adrenal tumors and ectopic ACTH secretion account for the remainder.

I. Clinical findings include truncal obesity, rounded face, fat deposits in the supraclavicular fossae and over the posterior neck, hypertension, hirsutism, amenorrhea, and depression. More specific findings include thin skin, easy bruising, reddish striae, proximal muscle weakness, and osteoporosis. Diabetes mellitus develops in some patients. Hyperpigmentation or hypokalemic alkalosis suggests Cushing's syndrome due to ectopic ACTH secretion.

II. Diagnosis is based on increased cortisol excretion and lack of normal feedback inhibition of ACTH and cortisol secretion.

A. The overnight dexamethasone suppression test (1 mg dexamethasone given PO at 11:00 PM; plasma cortisol measured at 8:00 AM the next day; normal plasma cortisol level <2 mg/dl) or 24-hour urine cortisol measurement can be done as a screening test. Both tests are very sensitive, and a normal value virtually excludes the diagnosis.

B. An abnormal screening test indicates the need to perform a low-dose dexamethasone suppression test. Dexamethasone, 0.5 mg PO q6h, is given for 48 hours, and urine cortisol is measured during the last 24 hours. Failure to suppress urine cortisol to less than the normal reference range is diagnostic of Cushing's syndrome. Testing should not be done during severe illness or depression, which may cause false-positive results. Phenytoin therapy also causes false-positive dexamethasone suppression test results by accelerating metabolism of dexamethasone. Random plasma cortisol levels are not useful for diagnosis, because the wide range of normal values overlaps those of Cushing's syndrome. After the diagnosis of Cushing's syndrome is made, tests to determine the cause are best done in consultation with an endocrinologist.

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