From the Guidelines
Hyperglycemia is not a recognized component of von Hippel-Lindau (VHL) syndrome, whereas hypoglycemia can be a potential issue due to pancreatic neuroendocrine tumors that may secrete insulin. VHL syndrome is a hereditary condition characterized by the development of tumors and cysts in multiple organs, including hemangioblastomas in the brain, spinal cord, and retina, as well as renal cell carcinomas and pheochromocytomas 1. The condition is caused by a mutation in the VHL gene, which plays a critical role in cellular oxygen sensing 1. While the primary manifestations of VHL disease include retinal hemangioblastoma, central nervous system hemangioblastoma, renal cell carcinoma, pheochromocytoma, and pancreatic neuroendocrine tumors, hyperglycemia is not typically associated with this condition 1.
Some key points to consider in the management of VHL syndrome include:
- Genetic testing of the VHL gene for at-risk individuals, including first-degree relatives of patients with known VHL disease or those with single or multifocal retinal hemangioblastomas 1
- Comprehensive surveillance, including regular blood glucose monitoring if pancreatic involvement is suspected, due to the potential for hypoglycemia caused by insulin-secreting tumors 1
- The clinical diagnosis of VHL disease is made using criteria based on family history and cardinal manifestations, such as retinal hemangioblastoma, central nervous system hemangioblastoma, pheochromocytoma, neuroendocrine tumors, and clear cell renal carcinoma 1
In terms of morbidity, mortality, and quality of life, it is essential to prioritize the early detection and management of VHL syndrome, including the potential for hypoglycemia, to prevent severe symptoms and improve patient outcomes 1.
From the Research
Pancreatic Involvement in Von Hippel-Lindau Disease
- Von Hippel-Lindau (VHL) disease is an autosomal dominant disorder characterized by the development of multiple tumors in the central nervous system and visceral organs, including the pancreas 2, 3, 4, 5.
- Pancreatic involvement in VHL disease is common, with a prevalence of 87.4%, and can present as simple cysts, serous cystadenoma, or neuroendocrine tumors (NETs) 2.
- NETs are a type of pancreatic tumor that can occur in VHL disease, and they can cause hormonal symptoms, including hyperglycemia 4, 5, 6.
- Hyperglycemia is not a direct symptom of VHL disease, but it can be associated with pancreatic NETs, which are a common feature of the disease 4, 5, 6.
Clinical Features and Management
- The clinical features of pancreatic involvement in VHL disease include the development of simple cysts, serous cystadenoma, and NETs, which can cause hormonal symptoms, including hyperglycemia 2, 3, 4, 5, 6.
- Management of VHL disease largely consists of surgical resection of symptomatic tumors, tumors prone to metastasize, or tumors causing hormonal symptoms, including hyperglycemia 4, 6.
- Early detection and management of pancreatic NETs are crucial to prevent metastasis and improve survival in patients with VHL disease 6.
Genetic and Molecular Aspects
- VHL disease is caused by germline mutations in the VHL tumor-suppressor gene, which plays a major role in regulating the oxygen-sensing pathway and targeting the hypoxia-inducible factor HIF for degradation in proteasome 4, 5.
- Somatic inactivation of the VHL gene is the main molecular event in most sporadic renal cell carcinomas, and targeted therapy with drugs that block angiogenesis has shown promising results for renal cell carcinomas and pancreatic NETs in VHL patients 5, 6.