Unlikely Coexistence of Sporadic Pheochromocytoma and Bilateral Macronodular Adrenal Hyperplasia: A Challenge to Manage

Background: The incidence of bilateral macronodular adrenal hyperplasia (BMAH) is unknown, but growing in an era of increased utilization of imaging. Coexistence of BMAH and pheochromocytoma has not previously been reported. Clinical Case: A 63-year man presented with enlarging left chest-wall mass found to have a poorly differentiated sarcoma. Staging PET/CT identified a hypermetabolic 2.0 cm left adrenal nodule with SVU of 16.6 concerning for metastasis. Hormonal evaluation included dexamethasone suppression test with 7AM serum cortisol of 24.7 ug/dL (<1.8 ug/dL) without dexamethasone level, serum ACTH <5.0 pg/mL (7.2–63 pg/mL), plasma metanephrine of <0.20 nmol/L (0–0.49 nmol/L), and plasma normetanephrine of 0.76 nmol/L (0.00–0.89 nmol/L). Biopsy of this left adrenal nodule was consistent with pheochromocytoma. By history, he lacked any classical symptoms of pheochromocytoma. Repeat testing demonstrated only slight elevations in normetanephrine (1.3 nmol/L and 1.2 nmol/L); he remains asymptomatic at follow-up 4 months later. However, history and exam revealed central obesity, thin skin, type 2 diabetes mellitus on insulin, and hypertension controlled on three agents concerning for Cushing’s. Repeat evaluation showed AM cortisol of 17.9 ug/dL (<1.8 mcg/dL) with dexamethasone level of 917 ng/dL (180–550 ng/dL), ACTH of 6.4 pg/mL with concordant cortisol of 23.1 ug/dL, and 24 hour urine collection with 0.98 L volume, creatinine of 0.58 g/24h (1–2 g/24hr), and urinary free cortisol of 67 ug/24h (3.5–45) altogether suggesting ACTH-independent hypercortisolism. On review of CT abdomen, he has bilateral adrenal nodules measuring >1cm with bilateral gland enlargement consistent with BMAH. Resection of his left adrenal gland was not pursued due to cormorbidities as well as biochemically-silent nature of his pheochromocytoma. To manage his hypercortisolism, he was recently initiated on osilodrostat after completing radiation therapy for his chest-wall sarcoma. Conclusion: This is the first case demonstrating clinical, biochemical, and imaging results consistent with bilateral macronodular adrenal hyperplasia and hypercortisolism also found to have a clinically and biochemically silent, biopsy proven pheochromocytoma. This is also a unique use of osilodrostat to manage BMAH.