A KINDRED WITH A VARIANT OF MULTIPLE ENDOCRINE NEOPLASIA TYPE-1 DEMONSTRATING FREQUENT EXPRESSION OF PITUITARY-TUMORS BUT NOT LINKED TO THEMULTIPLE ENDOCRINE NEOPLASIA TYPE-1 LOCUS AT CHROMOSOME REGION 11Q13

Acromegaly is uncommon in kindreds with multiple endocrine neoplasia t ype 1 (MEN1), whereas primary hyperparathyroidism (PHP) has the highes t penetrance of any endocrinopathy. We report an unusual MEN1 kindred with frequent expression of pituitary tumors and a low penetrance of P HP. Four members were found to have disease: PHP in generation I, acro megaly (2 cases) in generation II, and hyperprolactinemia associated w ith a pituitary tumor in generation III. There was no evidence for PHP in 1 patient with acromegaly (age 60 yr), the patient with hyperprola ctinemia and the pituitary tumor (age 22 yr), and 1 asymptomatic oblig ate carrier (age 50 yr). Screening of 26 members revealed the possible diagnosis of PHP in 1 family member in generation II and possible ear ly acromegaly in 2 members of generation III with elevated serum conce ntrations of insulin-like growth factor I and insulin-like growth fact or-binding protein-3 but normal patterns of pulsatile GH release. Alth ough the predisposing genetic defect in typical MEN1 families has prev iously been mapped to chromosome location 11q13 without evidence of he terogeneity among the 87 families analyzed, linkage of disease in this family to the MEN1 region is unlikely based on haplotype analysis. Lo calization of the gene(s) responsible for disease in such atypical fam ilies may aid in the understanding of the pathogenesis of MEN1. In add ition, further study of the earliest changes in patterns of pulsatile GH release in familial acromegaly may allow more insight into the path ogenesis and natural history of this disease.