Pancreatic Manifestations of Von Hippel Lindau: A Case Series

Abstract

Introduction: Von Hippel Lindau (VHL) syndrome is an autosomal dominant genetic disorder with a wide phenotypic expression. Few case reports describe the relationship between VHL and exocrine pancreatic insufficiency (EPI), and regulation of pancreatic endocrine function by the VHL gene has only been described in animals. However, close to 60 percent of patients show pancreatic involvement. Our aim is to corrrelate pancreatic findings with the presence of exocrine and/or endocrine function in a well genotyped and phenotyped group of patients with this disease. Methods: We performed a retrospective medical record review of patients with VHL in our Pancreatic Disease Center. We collected demographic data, genetic mutations, organ involvement, pancreatic imaging findings, degree of cyst involvement, clinical evidence of EPI, fecal elastase-1 (FE-1) and evidence of endocrine insufficiency (HbA1c). Results: We identified a total of 14 patients. Ten patients were women and four were men with a median age of 35 (19-70). Twelve had a documented genetic mutation, of which 11 had a strong family history of VHL. Four had lesions in the pancreas highly suggestive of pancreatic neuroendocrine tumors and one had a lesion suggestive of a serous cystadenoma. Simple pancreatic cystic lesions were present in nine patients. In this group, seven had complete cystic replacement of the pancreas (median age 48 (23-70)), of which two had significant duodenal compression causing gastric outlet obstruction requiring laparoscopic gastrojejunostomy. Within the same group, three had symptoms suggestive of EPI and two had a FE-1 consistent with severe EPI (≤ 50 and 88 with normal being > 200 μg/g). One provided an inadequate sample. Pancreatic enzyme replacement therapy was initiated with improvement in symptoms including weight gain. Four patients with complete cystic replacement of the pancreas were screened for EPI, three had a normal FE-1 and one provided an inadequate sample. Among the three patients with symptomatic EPI, all had a HbA1c measured and two were newly diagnosed with type 3c diabetes (HbA1c 6.8 and 8.1). Conclusion: Complete cystic replacement of the pancreas is common in patients with VHL. Particular attention must be made for the early diagnosis of exocrine and endocrine pancreatic insufficiency, both of which were newly diagnosed in our cohort. Guidelines for screening and management of pancreatic involvement in patients with VHL are needed to improve and standardize quality of care.