The ultimate biochemical diagnosis of endocrine pancreatic tumours in MEN-1

Multiple endocrine neoplasia type 1 (MEN-1) is a well characterized hereditary syndrome with the occurrence of primary hyperparathyroidism (HPT) in combination with pancreatic-duodenal endocrine and anterior pituitary tumours. The diagnosis of MEN-1, the possible probands, necessitates the recognition of at least two or three lesions classically associated with the syndrome whilst only one of them is required for individuals belonging to established MEN-1 kindreds. A distinct feature of MEN-1 comprises the multiplicity of organ involvement, the multicentricity of tumours within the affected organs as well as the complex pattern of the clinical signs of these tumours and their sometimes temporarily variable profile of hormone excess. Thorough screening studies have demonstrated that the MEN-1 trait is biochemically detectable virtually two decades prior to clinically overt disease. The primary biochemical screening programme for MEN-1 includes serum prolactin and insulin growth factor 1 (IGF-1) for pituitary lesions, intact PTH and albumin corrected total serum calcium for the parathyroids and for duodenal/pancreatic tumours serum glucose, insulin, proinsulin, pancreatic polypeptide, glucagon, gastrin and plasma chromogranin A. Furthermore a standardized meal stimulatory test analysing serum polypeptides (PP) and gastrin is recommended. Our current primary screening procedure has yielded about 10% false positives when compared with RFLP data. Pancreatic endocrine tumour diagnosis must be biochemically established since radiology fails to show lesions in half of the patients. Pancreatic involvement in young MEN-1 patients is most consistently demonstrated by analysing serum insulin, proinsulin, PP as well as plasma glucagon chromogranin A levels, which have exhibited sensitivities of 56, 67, 37 and 60%, respectively. Serum PP is a non-specific marker of islet cell tumours that should be applied in conjunction with other peptide markers. Elevation of basal serum gastrin generally indicates the presence of advanced pancreatic tumour involvement or duodenal carcinoids. Early diagnosis of pancreatic endocrine tumours in MEN-1 is enhanced by the use of a standardized meal stimulation test with measurements of serum PP and gastrin response. This test was the most sensitive test and substantiated the presence of tumour in 75% of individuals whose mean age was 25 years. False-positive stimulation due to the meal test has been found in about 10% of previous investigated individuals. The diagnosis of MEN-1 pancreatic tumours is based on biochemical screening alone and it has been substantiated that an unequivocal rise in pancreatic tumour markers precedes radiological detection of these lesions by at least five years.