EXPRESSION OF THE MEN-1 GENE IN A LARGE KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE-1

In 1983 a large family;with MEN-1 (designated Tasman 1) was identified in Tasmania, Kindred screening and case follow-up over the subsequent 15 years has yielded data on over 160 MEN-1-affected patients. Hyperp arathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathologica l finding, Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gast rinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients. respectively. Metastatic gastroenterop ancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitar y disease developed in 19% of patients, Prolactinoma and 'nonfunctioni ng' adenoma account for 76 and 24%, respectively, of pituitary abnorma lities. Prolactinomas exhibit clustering within branches of the Tasman 1 kindred, Adrenal adenomas occur in 36% of patients. The majority of adrenal lesions are benign and nonsecretory and develop in associatio n with pancreatic neoplasia. Carcinoid tumours are uncommon but import ant malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to re cognition of MEN-1 in Tasman 1, complications of hyperparathyroidism a nd malignancy accounted for the majority of patient mortality, Since c ommencement of prospective screening, malignant GEP tumours and cardio vascular disease have become the most prevalent causes of death amongs t MEN-1-affected patients.