Endocrine Abstracts

Background: Catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla and the sympathetic ganglia are respectively referred to as pheochromocytomas and paragangliomas. The classic triad of symptoms in patients with pheochromocytoma (PHEO)consists of episodic headache, sweating, and tachycardia. Approximately one-half have paroxysmal hypertension; the rest have either primary hypertension or normal blood pressure. Clinicians should always consider PHEO when evaluating for secondary causes of hypertension, as missing this diagnosis can result in devastating complications, including death.

Clinical case: A previously healthy 53-year-old woman presented to her general practitioner with daily pulsatile bilateral frontal headaches persisting for 6 months, reporting different characteristics than her usual migraines. She complained of paroxysmal episodes of fatigue, palpitations, heat, sweating, and non-quantified weight gain in the previous months. Her past medical history was unremarkable, except for sporadic migraines since adolescence. She denied other relevant pathological medical history and had no previous hospital admissions or surgeries. She was not on regular medication or supplements. The physical examination was notable for a high diastolic blood pressure (BP) (137/106 mmHg) and a body mass index of 25.4 kg/m². Arterial hypertension was diagnosed, no treatment started, and she underwent investigation of secondary causes of arterial hypertension. During workup, high urinary metanephrines were detected and the abdominal MRI evidenced 2 nodular bilateral adrenal lesions. ¹⁸F-FDG-PET/CT scanning revealed mild to moderateuptake in both lesions without extra-adrenal uptake, the ¹²³I-MIBG scintigraphy demarcated the right lesion as suspicious and a CT-scan confirmed the heterogeneous nodular lesion on the right adrenal gland as suspicious for PHEO. A right adrenalectomy was performed with posterior resolution of symptoms and normalization of urinary metanephrines and histology confirmed a PHEO. Genetic testing became available five months after surgery and revealed a TMEM127 gene mutation detected in heterozigoty (NM_017849.3:c.410-2A > C p.?).

Discussion: TMEM127 is a negative regulator of mammalian target of rapamycin effector proteins, which promote cell growth and protein translation. Due to the high prevalence of multicentric and bilateral tumors and also renal cell carcinoma in TMEM127-related PHEO, periodic surveillance of the surgical site and the contralateral adrenal gland is mandatory. Moreover, cortical-sparing procedures should be favored in order to preserve adrenocortical function. This case report evidences the benefit of genetic testing for an accurate clinical management and treatment of patients and mutation carriers in TMEM127-related PHEO.