A Novel Neurofibromatosis Type 1 (NF1) Frameshift Mutation Associated With Atypical Hypotensive Pheochromocytoma: A...

Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor predisposition syndrome associated with an increased risk of pheochromocytoma. Pheochromocytoma typically presents with hypertension and catecholamine excess; however, atypical clinical features may occur. A 58-year-old Turkish male patient with clinically diagnosed NF1 was evaluated for persistent hypotension (approximately 90/50 mmHg) without classic catecholamine-related symptoms. Biochemical testing showed isolated elevation of plasma and urinary metanephrine, while normetanephrine and other catecholamines were within reference ranges. Imaging revealed a 3.7 cm left adrenal mass with increased uptake on Gallium-68 DOTA-octreotate Positron Emission Tomography/Computed Tomography (Ga-68 DOTATATE PET/CT). The patient underwent left adrenalectomy after carefully titrated preoperative alpha-blockade due to baseline hypotension. Histopathological findings were consistent with pheochromocytoma. Genetic analysis using next-generation sequencing identified a heterozygous NF1 frameshift variant (c.3322dup p.(Thr1108AsnfsTer9)), predicted to result in a premature termination codon and classified as pathogenic according to American College of Medical Genetics and Genomics (ACMG) / Association for Molecular Pathology (AMP) criteria. Postoperatively, metanephrine levels normalized and blood pressure remained stable. Pheochromocytoma in patients with NF1 may present with hypotension and isolated biochemical abnormalities. This possibility should be considered in the appropriate clinical context. The identified NF1 variant contributes to the existing literature on NF1-associated tumors.