SAT-501 Rare MEN2A Presentation: Simultaneous Manifestation Of The Complete Triad With Giant Pheochromocytoma

Abstract Disclosure: R. Lopez Fanas: None. L. Rasquin Leon: None. H. Angammana: None. M. Wysocki: None. R. Berkenblit: None. J.C. McAuliffe: Boston Scientific Consultant. N. Suda: None. B.Y. Wong: None. Introduction: Multiple Endocrine Neoplasia 2A (MEN2A) is a hereditary syndrome linked to RET proto-oncogene mutations and characterized by the triad of medullary thyroid cancer (MTC), pheochromocytoma (PCC), and primary hyperparathyroidism (PHPT). Concurrent presentation of all three features on initial evaluation, along with bilateral giant PCCs, is exceptionally rare. Case: A 44-year-old man, immigrating from Nigeria, presented with abdominal pain and sweating. Family history was significant for a twin sister with MTC, a sister with a thyroid mass, and his mother who died young of an unknown cause. He had a BP 169/103 mm Hg, HR 110 bpm, and exhibited marfanoid features with weight 74.4 kg, height 77", and arm span-to-height ratio 1.07. Abdominal imaging showed a 15 cm right adrenal mass compressing the inferior vena cava (IVC) and renal vessels, and a 10 cm left adrenal mass, both with heterogenous enhancement and non-contrast density of 39 and 35 Hounsfield units, respectively. Laboratory tests revealed: 24-hour urine total metanephrines 116,902 mcg/24h (182-739 mcg/24h), metanephrines (MN) 39,957 mcg/24h (58-203 mcg/24h), normetanephrines (NMN) 76,945 mcg/24h (88-649 mcg/24h), Chromogranin A 11525 ng/mL (<311 ng/mL), calcium 11.6 mg/dL (8.5 - 10.5 mg/dL), parathyroid hormone 99.7 pg/mL (20 - 80 pg/mL), and calcitonin 4692 pg/mL (<10 pg/mL). Aspiration biopsy of the thyroid nodules was consistent with MTC. Genetic testing confirmed MEN2A with pathogenic RET mutation Cys634Arg. He underwent bilateral adrenalectomy, complicated by right nephrectomy, IVC venotomy, and hemorrhagic shock. Pathology confirmed a 26 cm right PCC with Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) ≥6, and a 9 cm left PCC without malignant features. Discussion: We report an uncommon presentation of MEN2A linked to the Cys634Arg mutation in the RET gene. MTC occurs in nearly all patients with MEN2A and is generally the first manifestation. PCC and PHPT occur in 30%-50% and 20% of cases, respectively. It is rare for all three characteristic features to present simultaneously. In MEN2A, 72% of patients develop bilateral PCCs, 82% of which are synchronous. In this population, tumors typically have a median size of 3.8 cm, with average urinary MN levels near 5,800 mcg/24h. Giant PCCs (≥10 cm) are rare and less frequently associated with germline mutations. Our patient had giant PCC with a urinary MN level of 39,957 mcg/24h, which is 158 times the upper limit of normal, highlighting the unusual nature of this case. The rare presentation of the complete MEN2A triad, coupled with giant bilateral PCCs and markedly elevated MN, complicates medical management. Additionally, the presence of marfanoid features, associated with MEN2B, highlights the phenotypic variability within MEN syndromes. This case underscores the importance of recognizing atypical presentations of MEN2A. Presentation: Saturday, July 12, 2025