Ectopic Cushing Syndrome due to an Adrenocorticotropic Hormone-Producing Pheochromocytoma

Pheochromocytomas are rare catecholamine-secreting tumors arising from adrenomedullary chromaffin cells. Very rarely, they cosecrete adrenocorticotropic hormone (ACTH), causing ectopic Cushing syndrome. Because of its rarity, clinicians may not consider this etiology, despite the high morbidity associated with simultaneous catecholamine and cortisol excess. We present a case in which a systematic and methodical diagnostic approach led to identification and successful treatment of an ACTH-producing pheochromocytoma.

A 48-year-old man presented with altered mental status, rapid-onset hypertension and diabetes, profound hypercortisolism and proximal muscle weakness. Imaging revealed a 3.4 cm left adrenal mass and contralateral adrenal hyperplasia. ACTH, cortisol, and metanephrines were markedly elevated, and DOTATATE positron electron tomography demonstrated intense uptake in the adrenal mass, raising suspicion for an ACTH-secreting pheochromocytoma. After alpha-blockade, he underwent laparoscopic adrenalectomy. Postoperatively, ACTH became undetectable and he developed transient adrenal insufficiency, confirming cure. Pathology showed pheochromocytoma with positive ACTH staining. His hypertension, diabetes, mental status, and myopathy improved, and genetic testing for hereditary syndromes was negative.

ACTH-secreting pheochromocytomas can present with abrupt and severe hypercortisolism that may overshadow adrenergic symptoms. Clues include profound ACTH elevation, abnormal dexamethasone suppression test, elevated metanephrines, and a unilateral adrenal mass with contralateral adrenal hyperplasia. Early recognition is essential, considering higher morbidity associated with dual secretion of catecholamines and cortisol.

ACTH-producing pheochromocytoma is an uncommon but important cause of ectopic Cushing syndrome. Incorporating this entity into the differential diagnosis of rapidly progressive hypercortisolism enables timely intervention and reduces morbidity associated with combined catecholamine and cortisol excess.