Bilateral Pheochromocytoma in a BRCA2 Carrier: Coincidence or Emerging Association?

Pheochromocytomas are rare catecholamine-secreting tumours of adrenal origin. Bilateral pheochromocytomas (BPs) occur more commonly in familial or syndromic contexts such as MEN2, VHL, or SDHx mutations. However, association with BRCA2 mutations has not been widely reported.

We present a 55-year-old hypertensive male with persistent palpitations and sweating. Despite antihypertensive therapy, symptoms persisted. Biochemical analysis revealed elevated 24-h urinary metanephrines (1,705 µg/day), while serum cortisol and aldosterone were normal. Imaging (CECT and MRI) revealed bilateral adrenal masses suggestive of adenomas. GA68 DOTATATE PET confirmed somatostatin receptor (SSTR)-avid bilateral adrenal lesions. A bilateral adrenalectomy was performed, and histopathology confirmed pheochromocytoma. Genetic testing via whole-exome sequencing identified a BRCA2 variant of uncertain significance (VUS) on chromosome 13. Postoperatively, the patient remains normotensive on single-agent antihypertensive therapy and is on lifelong steroid replacement.

While pheochromocytoma is often linked with mutations in RET, VHL, and SDHx genes, BRCA2 is primarily associated with breast and ovarian malignancies. Emerging evidence suggests a potential role of BRCA2 mutations in adrenal tumorigenesis. This case may represent the first reported BP associated with a BRCA2 VUS. While causality cannot be established, the finding warrants further investigation into potential genotype-phenotype correlations.

Our report expands the phenotypic spectrum of BRCA2 variants and underscores the importance of genetic screening in bilateral adrenal tumours. Recognition of such rare associations is critical for genetic counselling, surveillance, and tailored management.