Self-Treatment: Infarction of an Adrenal Pheochromocytoma with ACTH-dependent Cushing Syndrome Resulting in Biochemical Cure

Introduction:
Pheochromocytomas (PCCs) are rare malignancies associated with catecholamine-secretion, however can rarely secrete other substances including adrenocorticotropin hormone (ACTH). Here we present the first reported case of an ACTH-producing PCC, which biochemically resolved following infarction from an esophageal bleed.

Case Description:
A 65-year-old man with a history of hypertension presented to the emergency room after he was found to have a potassium of 2.9 at urgent care. He reported two months of weight loss, progressively worsening uncontrolled hypertension and left lower quadrant pain. CT Imaging revealed right renal mass and left 4.8cm adrenal mass. Labs revealed 24-hour urine metanephrines 4333 mg and normetanephrines 2740 mg, with plasma metanephrine 2.66 nmol/L and normetanephrine 4.09 nmol/L. Also found to have elevated ACTH 378.0 pg/mL, DHEA-S 1071.7 mg/dL and positive low-dose dexamethasone test. Plasma CRH unable to be obtained. PCC subsequently became the working diagnosis with a concomitant ACTH-dependent Cushing syndrome of unknown source. MRI was negative for anterior pitutary pathology and CT chest was negative for intra-pulmonary pathology. While awaiting surgical removal of suspected PCC, he developed a Mallory-Weiss tear from vomiting resulting in hemorrhagic shock. After this episode of shock and resuscitation, he improved clinically with reduction of hyperpigmentation and a decrease in insulin requirements from 80IU to 0IU daily. Follow-up labs were notable for plasma metanephrine 0.82, plasma normetanephrine 0.82, DHEA-S 27.6, and ACTH 38.7, all significantly decreased. Pre-surgery, patient appropriately underwent alpha, followed by beta blockade. Patient underwent resection of the adrenal mass, which was consistent with PCC with areas of infarction and hemorrhage, but negative for ACTH stain, on pathology. Following adrenalectomy, he developed adrenal insufficiency with resulting moderate rise in ACTH. The patient was discharged on his original anti-hypertensive regimen, and hydrocortisone. Annual biochemical screens are planned with eventual weaning of hydrocortisone.

Discussion:
Accounting for 5% of all ACTH-producing neuroendocrine tumors, the incidence of reported ACTH-producing PCCs remains less than 100 cases in current literature. In our case, despite having stained negative for ACTH on pathology, the patient met standards proposed by other authors for the diagnosis of ACTH-producing PCC, which includes 1) clinical/lab evidence of hypercortisolism; 2) elevated plasma ACTH; 3) evidence of PCC biochemically or via imaging; 4) resolution of symptoms of hormonal excess after adrenalectomy; 5) rapid normalization of plasma ACTH after adrenalectomy. In our case, symptoms and lab studies improved after infarction of the tumor, not requiring adrenalectomy for biochemical resolution. Surprisingly, an extensive literature review yielded no other reports of an ACTH-producing pheochromocytoma which hormonally resolved after infarct. Concomitant improvement in his catecholamines and Cushing syndrome indicated the PCC was the likely source of the ACTH production.