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
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.