Von Hippel Lindau disease (VHL) induces tumors of kidneys, central nervous system, pancreas and paragangliomas We report one case where ectopic Cushing syndrome revealed VHL. A 19-year old was referred for hirsutism and spaniomenorrhea revealing an ACTH-dependent Cushing syndrome. Mineralocorticoids, calcium metabolism, chromogranine A, calcitonine, pancreatic hormones and urinary 5-HIA were normal. Blood nor- and metanephrine were 5.12 μg/l (n<5) and 0.92 μg/l (n<0.66) respectively. CTscan and MRI showed 5 pancreatic lesions and one nodule of the left adrenal gland, all hypervascularized and uptaking in FDG TEP-scan. Retinal examination and cerebral MRI were normal. Total pancreatectomy and left adrenalectomy were performed, showing a pheochromocytoma and well-differentiated endocrine pancreatic tumors, with positive immunoreactivity for ACTH in 1 nodule, insulin in the 2nd and glucagon in the 3rd one, vascular emboli, venous sheathing, extension to peripancreatic fat and uncertain diagnosis of malignancy. A neomutation F119L of the VHL gene was identified. The post-operative imaging showed several infracentimetric lesions: angioblastomas of the spinal cord, cystic and solid tumor of the left kidney, tumor of the right adrenal gland uptaking MIBG. During the 1st year post-surgery, post-surgical corticotrope insufficiency regressed. Daily insulin need dramatically decreased. C-peptide level proved to be in the normal range, leading to discontinuation of insulin. Abdominal CT, FDG-Pet, Octreo- and GLP1receptor scans were normal. Conclusion i) Less than 15% of the VHL are associated with an endocrine pancreatic tumor, exceptionally secreting ACTH. ii) The post-surgical detectable C-peptide with insulin weaning and multiple immunohistochemical staining argues for distant metastasis or ectopic metaplasia, not visible by imagery techniques. iii) This case report also raises the question of the etiology of pancreatic tumors when associated with adrenal tumor(s) (metastases, MEN1, VHL, neurofibromatosis) and of the role of the VHL-protein, an oxygen-sensing protein in the endocrine cells development.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology