MON-376 A Novel Mutation in VHL Gene as Posible Cause of Metastasic Pheocromocytoma

• Published in: Journal of the Endocrine Society 2019-04, Vol.3 (Supplement_1)
• Main Authors: Montes Barrón, Diego, Quintanilla Flores, Dania, De los Santos Aguilar, Ramon, De la Riva Espinoza, Claudia, Rodríguez Romo, Anabel, Garcia Tuomola, Aili, Reza-Albarran, Alfredo
• Format: Article
• Language: English
• Subjects: Adrenal
• ISSN: 2472-1972; 2472-1972
• DOI: 10.1210/js.2019-MON-376

A 62-year-old woman with no family history of hereditary diseases presented to the ER department in 2008 with the diagnosis of a subarachnoid hemorrhage that required urgent decompressive craniotomy. On February 2011, due to resistant hypertension, an abdominal CT scan was performed, revealing a left adrenal gland-dependent tumor of 70x86 mm, with additional increased normetanephrine levels in a 24-hour urine sample. Laparoscopic left adrenalectomy was performed on June 3, 2011, with a histological report of pheochromocytoma. It was also documented an elevation of iPTH (301 pg/ml) with corrected calcium of 11 mg/dL and phosphorus of 2.7 mg/dL. Parathyroidectomy was performed with the report of parathyroid adenoma. On January 2015, an abdominal CT scan was performed, revealing recurrence of the pheochromocytoma at the surgical site. A MIBG PET-CT confirmed the recurrence and detected a left retroperitoneal lesion close to the tail of the pancreas. Metastasectomy of the retroperitoneal lesions, distal pancreatectomy, and dissection of tumor adjacent to left kidney were performed with a histopathologic report of pheochromocytoma with nest pattern and extensive necrosis, negative margins, and three positive lymph nodes. During follow-up a significant increase of normetanephrine in 24-hour urine sample was documented (3 months after surgery). A Ga-DOTATOC PET-CT revealed the presence of hepatic metastases. In the 131-MIBG SPECT-CT performed one year later, a decreased height of C3 vertebral body with an abnormal concentration of the radiopharmaceutical in relation to secondary deposit was also found. On August 2017 the patient was treated with a therapeutic dose of 131-MIBG, achieving complete biochemical remission during 14 months of follow-up. On March 2018 an Invitae Multi-Cancer Panel reported the germline variant C. 416C > G (P. Ser139Cys) related to VHL without mutations in other pathogenic genes related to pheochromocytoma. VHL c.416C>G (at the cDNA level ) is a germline variant of Von Hipple Lindau (VHL) disease, also known as p.Ser139Cys (S139C) at the protein level. It results in the change of a Serine to a Cysteine (TCT>TGT), located in 3p25.3. This variant has been reported in population databases (rs587780732, ExAC 0.06%) and related to familiar erythrocytosis, monogenic diabetes (likely benign) and a type of autosomal recessive A1 deafness (uncertain significance); however, to our knowledge it has not been previously published in the literature as