SOMATOTROPHINOMAS IN MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 - A REVIEW OF CLINICAL PHENOTYPE AND INSULIN-LIKE GROWTH-FACTOR-I LEVELS IN A LARGE MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 KINDRED

PURPOSE: Within the spectrum of pituitary disease in multiple endocrin e neoplasia type 1 [MEN-1), widely disparate prevalence rates for soma totrophinomas have been described. Studies that combine multiple, smal l MEN-1 kindreds report pituitary disease in 60% to 65% of patients, s omatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on targe MEN-1 family screening programs have produced lower prevalence rates for pituitary adenomas (9% to 40%), of which somatotrophinomas comprise up to 14%. We sought to determine th e prevalence of both biochemical and clinically overt growth hormone ( GH) hypersecretion in the largest reported MEN-1 genealogy, the Tasman 1 kindred. PATIENTS AND METHODS: The Tasman 1 MEN-1 kindred contains 165 members with established MEN-1. We reviewed-the records of 124 MEN -1 patients for evidence of acromegaly or gigantism. To determine if c linical criteria underestimate the occurrence of biochemical GH hypers ecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). RESULTS: NO cases of acrom egaly or gigantism were detected in the 124 patients reviewed. Of the 33 patients screened with IGF-1, 13 had previously diagnosed pituitary lesions-11 prolactinomas and 2 nonsecretory lesions. The IGF-1 levels were normal in all patients studied. There were no significant differ ences in mean IGF-1 values between patients with and without pituitary lesions. CONCLUSIONS: This report represents the largest study of gro wth hormone secretion patterns thus far described in MEN-1. The appare nt absence of somatotrophinomas in a kindred of this size is unexpecte d. These results support the existence of kindred-specific MEN-1 pheno types. We conclude that the pathogenesis of GH-secreting adenomas in M EN-1 is influenced by secondary factors acting in synergy with the wel l-documented primary MEN-1 gene defect on chromosome 11q13.