Multiple endocrine neoplasia type 1 (MEN1) and type 4 (MEN4)

Pituitary adenomas (PAs) are associated with increased morbidity and mortality. The optimal delivery of services and the provision of care for patients with PAs require distribution of the resources proportionate to the impact of these conditions on the community. Currently, the resource allocation for PAs in the health care system is lacking a reliable and an up-to-date epidemiological background that would reflect the recent advances in the diagnostic technologies, leading to the earlier recognition of these tumours. To determine the prevalence, the diagnostic delay and the characteristics of patients with PA in a well-defined geographical area of the UK (Banbury, Oxfordshire). Sixteen general practitioner (GP) surgeries covering the area of Banbury and a total population of 89 334 inhabitants were asked to participate in the study (data confirmed on 31 July 2006). Fourteen surgeries with a total of 81,449 inhabitants (91% of the study population) agreed to take part. All cases of PAs were found following an exhaustive computer database search of agreed terms by the staff of each Practice and data on age, gender, presenting manifestations and their duration, imaging features at diagnosis, history of multiple endocrine neoplasia type 1 and family history of PA were collected. A total of 63 patients with PA were identified amongst the study population of 81,149, with a prevalence of 77.6 PA cases/100,000 inhabitants (prolactinomas; PRLoma: 44.4, nonfunctioning PAs: 22.2, acromegaly; ACRO: 8.6, corticotroph adenoma: 1.2 and unknown functional status; UFS: 1.2/100,000 inhabitants). The distribution of each PA subtype was for PRLoma 57%, nonfunctioning PAs 28%, ACRO 11%, corticotroph adenoma 2% and UFS 2%. The median age at diagnosis and the duration of symptoms until diagnosis (in years) were for PRLoma 32.0 and 1.5, nonfunctioning PAs 51.5 and 0.8, ACRO 47 and 4.5 and corticotroph adenoma 57 and 7, respectively. PRLoma was the most frequent PA diagnosed up to the age of 60 years (0-20 years: 75% and 20-60 years: 61% of PAs) and nonfunctioning PA after the age of 60 years (60% of PAs). Nonfunctioning PAs dominated in men (57% of all men with PA) and PRLoma in women (76% of all women with PA). Five patients (7.9%) presented with classical pituitary apoplexy, with a prevalence of 6.2 cases/100,000 inhabitants. Based on a well-defined population in Banbury (Oxfordshire, UK), we have shown that PAs have a fourfold increased prevalence than previously thought; our data confirm that PAs have a higher burden on the Health Care System and optimal resource distribution for both clinical care and research activities aiming to improve the outcome of these patients are needed.

This is a consensus statement from an international group, mostly of clinical endocrinologists. MEN1 and MEN2 are hereditary cancer syndromes. The commonest tumors secrete PTH or gastrin in MEN1, and calcitonin or catecholamines in MEN2. Management strategies improved after the discoveries of their genes. MEN1 has no clear syndromic variants. Tumor monitoring in MEN1 carriers includes biochemical tests yearly and imaging tests less often. Neck surgery includes subtotal or total parathyroidectomy, parathyroid cryopreservation, and thymectomy. Proton pump inhibitors or somatostatin analogs are the main management for oversecretion of entero-pancreatic hormones, except insulin. The roles for surgery of most entero-pancreatic tumors present several controversies: exclusion of most operations on gastrinomas and indications for surgery on other tumors. Each MEN1 family probably has an inactivating MEN1 germline mutation. Testing for a germline MEN1 mutation gives useful information, but rarely mandates an intervention. The most distinctive MEN2 variants are MEN2A, MEN2B, and familial medullary thyroid cancer (MTC). They vary in aggressiveness of MTC and spectrum of disturbed organs. Mortality in MEN2 is greater from MTC than from pheochromocytoma. Thyroidectomy, during childhood if possible, is the goal in all MEN2 carriers to prevent or cure MTC. Each MEN2 index case probably has an activating germline RET mutation. RET testing has replaced calcitonin testing to diagnose the MEN2 carrier state. The specific RET codon mutation correlates with the MEN2 syndromic variant, the age of onset of MTC, and the aggressiveness of MTC; consequently, that mutation should guide major management decisions, such as whether and when to perform thyroidectomy.

Multiple endocrine neoplasia-type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610-amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN1 will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.