Somatotrophinomas in multiple endocrine neoplasia type 1: A review of clinical phenotype and insulin-like growth factor-1 levels in a large multiple endocrine neoplasia type 1 kindred

Purpose Within the spectrum of pituitary disease in multiple endocrine neoplasia type 1 (MEN-1), widely disparate prevalence rates for somatotrophinomas have been described. Studies that combine multiple, small MEN-1 kindreds report pituitary disease in 60% to 65% of patients, somatotrophinomas accounting for 27% to 37% of total pituitary lesions. However, reports based on large 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 the 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 clinical criteria underestimate the occurrence of biochemical GH hypersecretion, a subset of 33 patients was assessed for elevated levels of serum insulin-like growth factor-1 (IGF-1). Results No cases of acromegaly 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 differences in mean IGF-1 values between patients with and without pituitary lesions. Conclusions This report represents the largest study of growth hormone secretion patterns thus far described in MEN-1. The apparent absence of somatotrophinomas in a kindred of this size is unexpected. These results support the existence of kindredspecific MEN-1 phenotypes. We conclude that the pathogenesis of GH-secreting adenomas in MEN-1 is influenced by secondary factors acting in synergy with the well-documented primary MEN-1 gene defect on chromosome 11q13.