Endocrine Abstracts

Introduction: Von Hippel–Lindau disease (VHLD) is an autosomal dominant neoplastic syndrome characterized by the development of multiple cancers and cists, including pheochromocytoma and islet cell tumors. Screening is mandatory for family members of index cases.

Case report: A 23-year-old male Caucasian was referred to Endocrine Department because of the recent genetic diagnosis of VHLD during familiar screening. The mutation c.482G>A(p.Arg161GIn) was identified in the exon 3 of VHL gene in heterozigoty. His mother, the index case, harboring the same mutation, was diagnosed and treated for bilateral pheochromocytoma, retinal angiomas and pancreatic cancer. His mother’s monozygotic twin was also diagnosed of VHLD and submitted to bilateral adrenalectomy, because of bilateral pheochromocytoma, photocoagulation of retinal angiomas and mastectomy because of breast cancer. The same VHL mutation was identified.

The patient was completely asymptomatic and physical examination was unremarkable.

Serum normetanephrine was slightly elevated: 200 nmol/dl (Reference value (RV) <80) but with normal suppression in clonidine test. Serum metanephrine and 24 h-urinary nor- and metanephrine were normal. There was no other endocrine dysfunction. NSE was 34 μg/l (RV<16). No vascular lesions were apparent on fundoscopic examination or CNS-RMN; a 3 cm T1-hypointense and T2-hyperintense nodular lesion was found anteriorolateral to L₃ vertebral body, suggestive of paraganglioma. Renal and adrenal CT scan identified a 2.5 cm lesion in the right gland suggestive of pheochromocitoma, confirmed by MIBG hyperfixation, that did not imaged the other lesion.

After careful pre-surgical preparation right adrenalectomy and excision of the left paravertebral lesion were performed, confirming the diagnosis of pheochromocytoma and paraganglioma respectively.

Conclusion: VHLD is a rare hereditary syndrome, due to an inactivating mutation of the VHL gene, a tumor suppressor gene. Pheocromocytoma is its most common endocrine manifestation. Our clinical report highlights the need for imaging at-risk patients, since they often are asymptomatic with normal catecholamine and cathecolamine metabolites levels.