Ectopic adrenocorticotropin production in bilateral pheochromocytomas

Ectopic ACTH production represents a subset of disease entities which lead to hypercortisolism and are due to ectopic ACTH secretion by organs/tumours other than the pituitary gland. Very few of these tumours are of adrenal origin. In rare cases unilateral pheochromocytomas have been observed as a cause of ACTH production. We describe a 53-yr-old female with arterial hypertension who presented with a cushingoid-habitus and serious recurrent hypertensive crisis. Laboratory studies indicated severe hypokalaemia (K 2,28 mmol/l), alkalosis, diabetes (HbA1c 11,8%), and random serum cortisols greater than 1400 nmol/l. ACTH levels were elevated at >62 pmol/l. The endocrinological investigation showed biochemical evidence of ectopic ACTH production (lack of regulation in Dexamethason-/CRH-Test). Unexspecedly urinary catecholamines were markedly elevated (Adr. >300 nmol/l, Noradr. >3500 nmol/l) leading to the diagnosis of a pheochromocytoma.

Several imaging techniques were performed. MRI of the sella region showed no pathological findings, abdominal CT-scan showed a 3 to 3, 5-cm left adrenal mass and a hypertrophic right adrenal. Total body MIBG-scan showed relevant staining in projection to both adrenals whereas PET-scan did not indicate any increased metabolism.

All together the diagnostic workup, including bilateral selective adrenal vein catheterization, indicated a bilateral pheochromocytoma with unilateral ectopic ACTH secretion of the left adrenal.

After alpha-blockade with phenoxybenzamine a bilateral adrenalectomy resulted in remission of the Cushing's syndrome and the arterial hypertension within an improved glucose metabolism as well as improved insulin sensitivity. Plasma ACTH, urinary cortisol and catecholamine excretion normalized post surgery.

Surprisingly pathological examination of both adrenals revealed pheochromocytomas which showed strong immunostaining for ACTH.

To our knowledge, this is the first description of a case with ectopic ACTH syndrome due to bilateral ACTH production in bilateral pheochromocytomas.