Case Presentation: We report a case of a 29 yo female whose initial clinical manifestation of pheochromocytoma/MEN was suspected due to an incidental discovery of bilateral adrenal lesions revealed by abdominal CT instead of a positive family history with relevant symptoms. Despite repeatedly presenting to the emergency department for episodic anxiety accompanied by hypertension, the patient was never assessed for possible pheochromocytoma/MEN, although the patient’s father had died due to metastatic MTC to liver secondary to MEN2A-RET mutation: exon 11, C634R (Cys634Arg); 1900T→ C (TGC>CGC); the paternal grandfather was believed to have MTC and the patient herself had the history of failure to seek relevant genetic counselling recommended in 2006. The plasma metanephrine was 301 pg/mL and normetanephrine 3291 pg/mL. The ultrasound guided thyroid FNA was positive for malignant cells consistent with MTC, positive for calcitonin, TTF-1 and CEA. By the time the patient was diagnosed and underwent total thyroidectomy, she had MTC with B/L cervical lymph node involvement with extranodal extension, B/L pheochromocytoma, HPTH and renal dysfunction.
Discussion: MEN2A is a rare genetic disorder (1 case per 30,000-50,000 persons in US) characterized by medullary thyroid carcinoma/MTC (95-100%), pheochromocytomas (30-50%) and primary hyperparathyroidism (10-20%), occasionally associated with Hirschsprung disease (2-5%) and cutaneous lichen amyloidosis. Transmitted as autosomal dominant with virtually 100% penetrance by biochemical testing, only 60-70% present with clinical symptoms. Pheochromocytoma, although usually benign, diagnosed at the same time as MTC or later, can serve as a pertinent window to the diagnosis of MEN, is easily missed due to intermittent symptoms and being a “great mimic”. The American Thyroid Association recommends genetic counseling and testing for RET germline mutations to first-degree relatives of patients with proven hereditary MTC. With preimplantation genetic diagnosis and prenatal chorionic villus sampling or amniocentesis techniques available, it becomes easier to limit the transmission of the syndrome and timely diagnosis to prevent life threatening consequences afterwards. However, people who do not pursue genetic testing should be counselled to mention the positive family history on every healthcare encounter even if unasked to help aid the diagnosis and timely treatment to limit complications.
Conclusions: MEN2A is a rare syndrome with significant morbidity and mortality, which can be limited by the available options of genetic testing in the indicated population. However, lack of follow up for genetic testing can veil the diagnosis particularly if the family history is missed, as in our case. The healthcare providers must consider all organic causes of anxiety in their differentials so as not to miss pheochromocytoma and MEN syndromes.