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Expression of the MEN-1 gene in a large kindred with multiple endocrine neoplasia type 1
J R Burgess1, T M Greenaway, J J Shepherd
1Department of Diabetes and Endocrine Services, Royal Hobart Hospital, Tasmania, Australia. jburges@postoffice.utas.edu.au
Abstract:
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. Hyperparathyroidism is present in over 60% of gene carriers by age 20 years and 95% by age 30 years. Hyperplasia is the characteristic pathological finding. Kaplan-Meier analysis indicates hyperparathyroidism recurs in the majority of patients despite near-total parathyroidectomy. Gastrinoma, 'nonfunctioning' pancreatic adenoma and insulinoma occur in up to 60, 50 and 10% of patients, respectively. Metastatic gastroenteropancreatic (GEP) tumours develop in up to 35% of family members, being frequent in some branches of Tasman 1, whilst rare in others. Pituitary disease developed in 19% of patients. Prolactinoma and 'nonfunctioning' adenoma account for 76 and 24%, respectively, of pituitary abnormalities. 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 association with pancreatic neoplasia. Carcinoid tumours are uncommon but important malignancies. Malignant thymic carcinoid occurs in male patients, whereas bronchial carcinoid occurs predominantly in women. Prior to recognition of MEN-1 in Tasman 1, complications of hyperparathyroidism and malignancy accounted for the majority of patient mortality. Since commencement of prospective screening, malignant GEP tumours and cardiovascular disease have become the most prevalent causes of death amongst MEN-1-affected patients.
Insights
Multiple Endocrine Neoplasia type 1 (MEN-1) screening in the Tasman 1 family reveals high rates of hyperparathyroidism and pancreatic tumors. Prospective surveillance has shifted mortality causes from hyperparathyroidism to malignant GEP tumors and cardiovascular disease.
Area of Science:
- Endocrinology
- Genetics
- Oncology
Background:
- Multiple Endocrine Neoplasia type 1 (MEN-1) is a hereditary endocrine disorder.
- The Tasman 1 family in Tasmania provided a unique cohort for studying MEN-1 progression.
- Long-term family screening is crucial for understanding MEN-1 manifestations and outcomes.
Purpose of the Study:
- To characterize the clinical spectrum and natural history of MEN-1 in the large Tasman 1 kindred.
- To identify the prevalence and progression of various tumors associated with MEN-1.
- To analyze changes in mortality patterns following the implementation of prospective screening.
Main Methods:
- Longitudinal family screening and case follow-up over 15 years.
- Kaplan-Meier analysis for recurrence rates of hyperparathyroidism.
- Detailed pathological and clinical data collection on affected individuals.
Main Results:
- Hyperparathyroidism affects over 95% of gene carriers by age 30, with hyperplasia as the characteristic pathology and high recurrence rates post-surgery.
- Gastroenteropancreatic (GEP) tumors (gastrinoma, nonfunctioning adenoma, insulinoma) occur in up to 60% of patients, with metastatic potential in 35%.
- Pituitary adenomas (prolactinoma, nonfunctioning) affect 19%, adrenal adenomas 36%, and carcinoid tumors are uncommon but significant malignancies.
Conclusions:
- MEN-1 in the Tasman 1 family presents with high penetrance of hyperparathyroidism and significant risk of pancreatic and pituitary tumors.
- Prospective screening has altered the primary causes of mortality, with malignant GEP tumors and cardiovascular disease becoming leading causes.
- Understanding the specific tumor profiles and mortality trends within families like Tasman 1 is vital for effective management and surveillance strategies.