Endocrine Abstracts

Introduction: Pheochromocytomas are catecholamine-producing tumors originated from the chromaffin cells of the adrenal medulla. Although usually sporadic, this tumors could be associated with germline mutations in about 40% of cases. TMEM127 has recently been identified as a novel gene conferring increased susceptibility to pheochromocytoma.

Case report: A 42-year-old woman was referred to our Hospital to perform a right adrenalectomy for pheochromocytoma. Months before she had hemoptysis, chest pain and arterial hypertension (180/120 mmHg) and performed a chest computed tomography that revealed a 6.5 cm right adrenal nodule with a density similar to liver parenchyma. During hospitalization, she presented several hypertensive peaks and performed an iodine-123MIBG Whole Body Scan that revealed increased uptake in the right adrenal gland. Urinary metanephrines and vanilmandelic acid were normal. She underwent phenoxybenzamine therapy and was submitted to right adrenalectomy by laparotomy. The histological exam confirmed the presence of a pheochromocytoma with probable aggressive biological behavior, proliferation index (Ki67) of 5% and preservation of the adrenal cortex. After the surgery, she presented normalization of blood pressure, normal values of urinary metanephrines and vanilmandelic acid and a slight elevation of chromogranin A, norepinephrine and 5-hydroxyindoleacetic acid. During the biochemical and imaging follow-up, the patient showed no signs of recurrence or new extra-adrenal foci and remains in regular surveillance without evidence of disease 7 years after surgery. A gene panel analysis was performed (SDHAF2,SDHB,SDHC,SDHD,VHL,MAX,TMEM127) and the c.202delG mutation in TMEM127 gene was found. A molecular study was carried out on first-degree relatives and two asymptomatic carriers (father and sister) were identified.

Discussion and conclusion: An increasing number of genes have been associated with familial pheochromocytomas/paragangliomas and are associated with different manifestations/risk of malignancy. Pheochromocytoma associated with this mutation is unilateral in 70% of cases and may be associated with the risk of extra-adrenal locations. We report the clinical case of a patient with familial pheochromocytoma with identified mutation in TMEM127 gene, present in heterozygosity. To the best of our knowledge, this is the first mutation in this gene described in the Portuguese population. The present case identifies an adrenal lesion with typical manifestations, with a histology suggestive of aggressive behavior, without manifestations of disease to date in the other two mutation carriers. These data emphasize the need for molecular study of a large panel of genes in patients with apparently sporadic pheochromocytoma.