SAT-316 MAX-Related Bilateral Pheochromocytoma Associated with Subclinical Adrenal Insufficiency: A Case Report

INTRODUCTION: Loss-of-function mutation in the MYC-associated factor X (MAX) gene causes hereditary pheochromocytoma (PCC) that are frequently bilateral or multifocal(1). Adrenal insufficiency (AI) associated with unresected bilateral PCC has not been previously described. We hereby present a case of subclinical AI in a patient with bilateral PCC. CLINICAL CASE: An otherwise healthy 30-year-old woman was found to have a pathogenic MAX gene mutation (c.228delG) after undergoing genetic testing for a significant family history of PCC in 3 relatives. She participated in high-intensity interval training 5 times per week and denied episodes of palpitations, flushing, diaphoresis, or dizziness, but endorsed frequent pulsatile tinnitus and morning headaches. She had a history of hypertension in late pregnancy which had been presumed gestational. Exam was notable only for manual BP 152/110 mmHg, HR 110 bpm, and a faint resting tremor. Lab work was consistent with PCC: plasma norepinephrine 12417 pg/mL (ref <874) and normetanephrine 26 nmol/L (ref <0.9); urine norepinephrine 3378 mcg/24h (ref <135) and normetanephrine 16620 mcg/24h (ref <500). AM cortisol was 10.9 mcg/dL (ref 5-20) with a high normal ACTH of 46 pg/mL (ref 0-46) and low DHEA-S of 23 mcg/dL (ref 75-530). She had no prior history of glucocorticoid exposure, and thyroid studies were normal. CT imaging revealed bilateral contrast-enhancing heterogeneous adrenal masses (R: 3.5 x 2.2 cm; L: 4.6 x 4.5 cm). She was treated with alpha- then beta-adrenergic blockade and subsequently underwent surgical removal of both adrenal tumors with sparing of the superior adrenal cortices bilaterally. Plasma and urine catecholamines and metanephrines normalized a week post-operatively, and she began to report fatigue and dizziness. Two weeks post-operatively, midday plasma levels of cortisol, DHEA-S, and ACTH were 6.3 mcg/dL, <15 mcg/dL, and 118 pg/mL, respectively. Standard-dose 250mcg ACTH stimulation test confirmed AI with peak cortisol of 15.1 mcg/dL. Replacement hydrocortisone was initiated with prompt resolution of symptoms. CONCLUSIONS: Individuals with a pathogenic MAX mutation require prompt screening for PCC as symptoms may be subtle despite significant biochemical abnormalities. Large PCCs may also impact hormone synthesis by the adjacent adrenal cortex. Even prior to surgery, this patient had subclinical AI as evidenced by a high-normal plasma ACTH and clearly low DHEA-S. The latter is the earliest adrenal steroid to decline in patients with primary or central AI(2). It is unclear whether her worsening adrenal function after surgery was a surgical complication or due to dramatic decline in circulating catecholamines. Regardless, loss of adrenal androgen production warrants close follow-up for development of AI. REFERENCES: (1) Burnichon N et al. Clin Cancer Res 2012;18:2828 (2) Sayyed Kassem L et al. JCEM 2012;97:3655