Cushing Syndrome

About Cushing Syndrome

Cushing syndrome results from chronic exposure to excess cortisol. Harvey Cushing described the condition in 1932. The most common cause is exogenous glucocorticoid medications prednisone, dexamethasone used for inflammatory conditions. Endogenous causes include Cushing disease pituitary ACTH producing adenoma, approximately 70 percent of endogenous cases, adrenal adenoma or carcinoma, and ectopic ACTH syndrome small cell lung cancer, carcinoid tumors. The clinical presentation is distinctive and includes central obesity with thin extremities, moon face rounded fullness, buffalo hump fat pad on upper back, purple abdominal striae stretch marks, proximal muscle weakness, easy bruising, thin fragile skin, acne, hirsutism in women, menstrual irregularity, decreased libido, hypertension, diabetes mellitus, osteoporosis, mood changes depression, irritability, emotional lability, and cognitive impairment. A key clinical clue is the contrast between the appearance and the patient feeling unwell. Diagnosis requires confirming hypercortisolism through elevated 24 hour urine cortisol, late night salivary cortisol, or failure to suppress cortisol on the low dose overnight dexamethasone suppression test. Once confirmed, ACTH levels distinguish ACTH dependent from independent causes. Pituitary MRI, adrenal CT, and inferior petrosal sinus sampling help localize the tumor. Treatment involves gradually reducing glucocorticoid medication where clinically possible, under medical supervision because stopping suddenly can be dangerous, transsphenoidal surgery for pituitary adenomas, adrenalectomy for adrenal tumors, and surgery or therapy for ectopic ACTH sources. Untreated Cushing syndrome historically carried high mortality.