Endocrine Abstracts

Pheochromocytoma is a rare catecholamine producing neuroendocrine tumor arising from the adrenal medulla. Approximately 40% of cases are hereditary and the remaining are sporadic. There are several familial syndromic disorders associated with phaeochromocytoma including: von Hippel-Lindau (VHL) syndrome, multiple endocrine neoplasia type 2 (MEN2) and, neurofibromatosis type 1 (NF1). Bilateral phaeochromocytoma should prompt suspicion of a hereditary familial syndrome such as MEN2 or VHL or SDHx or less commonly associated with inherited pathogenic variants in genes including; TMEM127, NF1, or MAX. We hereby present a case of bilateral phaeochromocytoma heralding a new diagnosis of MEN2 A in a kindred. A 32-year female, who had a past medical history of goitre, Grave’s thyrotoxicosis, supra ventricular tachycardia/atrial flutter, diabetes mellitus and hypertension was investigated for secondary causes of hypertension. She had a history of hypertension, palpitations, on and off headaches and anxiety. Her mother was also diagnosed with hypertension at the age of 29 years. Other than hypertension and a palpable goitre, there were no other remarkable clinical findings. Biochemical testing revealed elevated plasma metanephrines, normetanephrines and 3 methoxytyramine levels at 2039, 148087 and 1703 pmol/l respectively. Subsequent MRI imaging identified large bilateral indeterminate adrenal masses without evidence of signal drop out. A diagnosis of bilateral phaeochromocytoma was confirmed and the patient was planned for laparoscopic bilateral adrenalectomy. After adequate alpha blockade with doxazocin, carvedilol was added for blood pressure control. Tumor multi-focality prompted testing for suspected familial syndromes. The calcium levels were mildly raised (2.63 mmol/l) with unsuppressed PTH (4.13 pmol/l) and a fasting calcitonin level was 157.90 ng/l. The patient underwent an uncomplicated bilateral laparoscopic adrenalectomy. The histopathology samples showed bilateral phaeochromocytoma and an extra adrenal sympathetic para-ganglioma in infra renal aortic nodal area. Post operatively, due to elevated fasting calcitonin, she underwent a total thyroidectomy which confirmed bilateral, nodal metastatic medullary carcinoma of thyroid, c-cell hyperplasia, and diffuse parathyroid hyperplasia in a single gland. The genetic analysis was positive for a pathogenic RETc.1900T>G p.(Cys634Gly) variant. Her three children (13, 9 and 7 years) were also found to have inherited the RET variant and are awaiting prophylactic thyroidectomy and her father has also been diagnosed with the same variant and medullary thyroid carcinoma and is awaiting surgery. This case highlights the association of bilateral phaeochromocytoma with familial syndromes and importance of genetic analysis as phaeochromocytomas may be the presenting tumor phenotype in endocrine neoplasia syndromes such as MEN2A.