Diabetic ketoacidosis associated with pancreatic involvement in a patient with von Hippel-Lindau syndrome: a case report.

BACKGROUND: Von Hippel-Lindau (VHL) disease is a rare autosomal dominant disorder predisposing individuals to multisystem neoplasms. While pheochromocytoma is a well-recognized endocrine manifestation of VHL, pancreatic involvement leading to clinically significant endocrine dysfunction is less frequently emphasized. We report a case of VHL syndrome in which diabetic ketoacidosis (DKA) occurred in the context of underlying pancreatic pathology, highlighting a potential but underexplored metabolic complication in these patients. CASE SUMMARY: A 31-year-old man came to the emergency department with a three-year history of polydipsia, polyuria, and hyperglycemia, and was diagnosed with diabetic ketoacidosis (DKA). His history included resection of cerebellar hemangioblastoma in 2009 and again in 2017, as well as subtotal pancreatectomy (head and body) for pancreatic lesions in 2017. At that time, his blood glucose was normal. His mother and maternal aunt both had hemangioblastoma. During this admission, we found severely impaired islet function in the residual pancreatic tail. Autoimmune diabetes was ruled out by negative anti-GAD, anti-IA-2, and anti-ZnT8 antibodies. There was no sign of infection or steroid use. Genetic testing showed a heterozygous deletion in exon 3 of the VHL gene, confirming VHL syndrome. With no other triggers identified, we attributed the DKA to acute decompensation from markedly reduced beta-cell reserve, likely due to both prior pancreatic resection and chronic VHL-related pancreatic disease. However, without serial imaging or histopathology to confirm progressive changes in the remnant tail, we could not establish a definitive causal relationship. CONCLUSION: This case highlights that DKA can occur as an acute metabolic decompensation in patients with VHL-related pancreatic disease, particularly in those with prior pancreatic resections and progressive beta-cell loss over time. Nevertheless, the exact pathophysiological link between VHL-associated pancreatic involvement and the onset of DKA remains speculative and likely multifactorial. Clinicians should maintain vigilance for endocrine pancreatic insufficiency in VHL patients who present with unexplained hyperglycemia, even in the absence of a prior diabetes diagnosis. Further studies and accumulated case evidence are needed to clarify the mechanisms and risk factors for DKA in this specific population.