Expression of the MEN‐1 gene in a large kindred with multiple endocrine neoplasia type 1

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.

Multiple endocrine neoplasia type 1 in Northern Finland; clinical features and genotype–phenotype correlation

“…Similar to the findings in a Tasmanian kindred study (2), however, when NFPTs were analysed alone they were not associated with advancing age. Our findings of age-related penetrance of other various MEN1 lesions are in agreement with previous studies (2,4,5,30). In the present study, the peak of the prevalence of pituitary tumours is reached at around 60 years of age (Fig.…”

“…The most frequent manifestation of MEN1 is primary hyperparathyroidism (PHPT) occurring in 82-95% of patients, while enteropancreatic tumours and anterior pituitary adenomas are found in 27-75% and 19-65% respectively (1)(2)(3)(4)(5)(6). Adrenal lesions are seen in 5-40% (1, 2, 6, 7) and neuroendocrine tumours of the gastrointestinal tract, bronchus or thymus in 4-9% of patients (1,2,6). Leiomyoma of various sites and angiofibroma, collagenoma and lipoma of the skin are also seen in association with MEN1 (8,9).…”

Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis

“…The prevalence of thNETs among MEN1 patients is 2-8% (Teh et al 1997, Burgess et al 1998b, Gibril et al 2003, Goudet et al 2011, Sakurai et al 2013. Approximately one-fifth of all thNETs are MEN1-related (Teh et al 1997), therefore the diagnosis of a thNET should always prompt further evaluation of a possible underlying MEN1 syndrome (de Laat et al 2012).…”

Cell cycle control of pituitary development and disease

“…The MEN-1 syndrome is characterized by predisposition to pituitary adenomas, parathyroid hyperplasia, and pancreatic endocrine tumors. Pituitary adenomas affect between 25 and 30% of MEN-1 patients (Burgess et al 1998). These patients display germ line mutations in the MEN1 gene, which increase the susceptibility to all major pituitary adenoma subtypes.…”