Bilateral Pheochromocytoma with a Novel Pathogenic Variant in the MAX gene: A Case Report

Abstract

Pheochromocytomas and paragangliomas syndrome are grouped into three specific disease clusters based on their underlying genetic alterations. Pathogenic variants affecting the myelocytomatosis-associated factor X (MAX) gene predispose pheochromocytomas and paragangliomas syndrome to occur at younger ages, with more than half having bilateral pheochromocytomas. We report a case of bilateral pheochromocytomas with a novel pathogenic variant identified in the MAX gene (c.234_235dup). This young male was found to have a huge left suprarenal mass after he presented with severe hypertension and myocardial infarction. His endocrine workup confirmed a diagnosis of pheochromocytoma as evidenced by elevated levels of normetanephrine, metanephrine, and 3-methoxytyramine in the urine. CT of the adrenal glands revealed bilateral adrenal masses; the widest diameter for the left adrenal mass was almost 8 cm whereas for the right one was 2 cm. ⁶⁸Gallium-DOTATATE functional imaging showed significant uptake in the left adrenal mass, but indeterminate on the right, and no significant uptake was seen elsewhere to suggest metastatic lesions. He did not have syndromic features associated with multiple endocrine neoplasia, neurofibromatosis or von Hippel Lindau disease. The collective findings raised the clinical dilemma of whether unilateral or bilateral adrenalectomy should be pursued. The detection of pathogenic MAX gene was therefore crucial in guiding personalized treatment strategy. Following the bilateral adrenalectomy, his hypertension was cured. Annual biochemical screening and 2-yearly MRI imaging to look for recurrence of pheochromocytomas were planned according to international consensus.

Keywords: adrenalectomy; genetic predisposition to disease; hypertension; pheochromocytoma.

Figure 1

Axial view of the contrasted adrenal-directed CT during the venous phase showed bilateral adrenal masses of lipid-poor content, measuring in size [left: 7.1 x 7.5 x 7.4 cm; right: 2.0 x 1.1 x 1.8 cm] (yellow arrows).

Figure 2

Axial view of the ⁶⁸Gallium-DOTATATE PET-CT showed an avid left adrenal mass (SUVmax 45.0) with necrotic centre whereas the right adrenal nodule was still within the physiological uptake (SUVmax 19.6) (blue arrows).

Figure 3

Schematic diagram of MAX gene mutation in the patient. UTR, untranslated region.

Figure 4

The gross specimen showed a huge, well-encapsulated left adrenal mass and a smaller right adrenal nodule.