Prospective screening in multiple endocrine neoplasia type 1

To assess the age of clinically detectable onset of multiple endocrine neoplasia type 1 (MEN 1), 88 members of four families were invited to participate in a ten-year biochemical screening program. Evidence for clinically detectable MEN 1 was found in adolescence. Pancreatic endocrine dysfunction constituted the presenting lesion in a majority of these individuals. The age at diagnosis of pancreatic endocrine tumors averaged 25 years and was lowered by almost two decades by prospective investigation. Furthermore, the penetrance of the pancreatic endocrine and parathyroid lesions equaled the penetrance found in autopsy studies. The use of a standardized meal stimulation test with the measurement of serum pancreatic polypeptide (PP) and gastrin responses resulted in diagnostic sensitivities of 75% and 100%, respectively. In addition to basal serum PP and insulin values, the proinsulin level was predictive for early pancreatic involvement in MEN 1. Serum gastrin was another useful tumor marker but only in the patients with pancreatic tumors diagnosed outside the prospective investigation. Two of the four MEN 1 kindreds selected for the screening investigation displayed homogeneity within families with respect to the profile of peptide excess and malignant potential of the pancreatic endocrine lesion, while the remaining kindreds demonstrated variable MEN 1 traits.