Ectopic Adrenocorticotropic Hormone Production by a Noncatecholamine Secreting Pheochromocytoma

Abstract

Ectopic secretion of adrenocorticotropic hormone (ACTH) is an infrequent cause of Cushing’s syndrome. There are few reports of pheochromocytoma causing the ectopic ACTH syndrome. These tumors also produce catecholamines.1, 2 To our knowledge we report the first case of the ectopic ACTH syndrome caused by a noncatecholamine secreting pheochromocytoma. CASE REPORT A 52-year-old woman was admitted to the hospital with severe hypokalemia. She described a monthlong history of weight gain, muscle weakness, polyuria, polydipsia and emotional lability. She denied symptoms of adrenergic hyperactivity. Physical examination revealed a cushingoid phenotype and hypertension. Laboratory testing showed severe hypokalemia (1.5 mEq./l., normal 3.5 to 5), metabolic alkalosis (pH 7.6, normal 7.35 to 7.45; bicarbonate 42.9 mEq./l., normal 21 to 28) and blood glucose of 161 mg./dl. (normal 70 to 110). Urinary free cortisol was greater than 2,000 g. per day (normal 28.5 to 213.7), plasma ACTH was 323 pg./ml. (normal 9 to 46) and serum cortisol was 53 g./dl. (normal 5 to 25) with failure of suppression after high dose dexamethasone suppression test. Computerized tomography (CT) of the abdomen demonstrated a left adrenal mass measuring 4.2 4.5 cm. On magnetic resonance imaging (MRI) the left adrenal gland showed high signal intensity on T2-weighted image. 131 Iodine metaiodobenzylguanidine (MIBG) scintigraphy revealed higher uptake in the left adrenal gland. Urinary and plasma catecholamine levels, urinary metanephrines and vanillylmandelic acid excretion were consistently within normal limits. The patient underwent left adrenalectomy and a 4.2 cm. neoplasia was removed. Pathological examination of the tumor demonstrated a typical pheochromocytoma. Immunostaining of tumor cells was markedly positive for chromogranin and ACTH antibodies, but negative for vimentin, cytokeratins and melan-A (see figure). ACTH level in the tumor was extremely elevated, and ACTH messenger RNA was isolated by reverse transcriptase-polymerase chain reaction from the tumor cells. Postoperatively, signs and symptoms of Cushing’s syndrome resolved, with normalization of basal and dynamic cortisol, and ACTH, blood pressure, potassium and glucose levels. DISCUSSION