Endocrine Abstracts

Neuroendocrine tumor (ENET) is a distinct term and includes specific selected tumors of the foregut, midgut and hindgut. The term separates other neurocrest-derived tumors likewise pheochromocytomas, paragangliomas as well as medullary thyroid carcinoma and parathyroid adenoma. There are sporadic and hereditary ENETs. The prominent hereditary group of ENETs forms the syndrome of multiple endocrine neoplasia type 1 (MEN1). Other ENETS are regarded as sporadic.

The Preventive Care Unit of the Freiburg University Medical Center has focused over years on pheochromocytoma-associated syndromes including von Hippel-Lindau disease (VHL). Among the major manifestations of VHL are pancreatic islet cell tumors (ICT), thus forming a third group of ENET patients. Both genes, MEN1 and VHL have been identified. We have subjected patients with pancreatic islet cell tumors to genetic screening of the genes MEN1 and VHL.

The NET registry included 68 patients with pancreatic neuroendocrine tumors. These 68 subjects comprised 28 women and 40 men diagnosed with ICT at age 12–82 (mean 59 years). Twenty three functional tumors are registered, 13 insulinomas, 3 VIPomas, 2 glucagonomas, 1 gastrinoma and 4 tumors without specification. Moleculargenetic analysis revealed 4 patients with MEN1 germline mutations. In 36 patients no MEN1 and no VHL mutation was found. These patients and tumors were classified as sporadic.

The VHL registry included 23 subjects had ICT. Gender was female in 15 and male in 8 subjects. All these 30 patients were primarily symptomatic for other VHL-associated tumors but not because of ICT. Single ICT was present in 19 subjects, whereas in 4 subjects multiple tumors were present. Tumor diameter varied from 0.5 to 15 cm. Insulin, C peptide and gastrin were measured in 10 cases, but elevated C peptide and gastrin was only found in one subject. This patient had malignant ICT. Transformation from benign to malignant ICT was observed in 2 subjects at age 24 and 61 years respectively. Malignant tumors were found to be statistically larger than benign tumors. malignant. Moleculargenetic analyses revealed germline VHL mutations in all patients with VHL-associated ICT. There are 20 different mutations, 13 missense, 6 truncating mutations and one large deletion comprising exon 1. Of note, there was a clustering of mutations in nucleotides 691–713 (14/30 subjects) or nucleotides 666–761 (21/30 subjects).