Disease relevance of Multiple Endocrine Neoplasia Type 1

• NmcA shares the highest amino acid identity (50%) with the extended-spectrum class A beta-lactamase MEN-1 from E. coli [1].
• A patient had a parathyroid adenoma and prolactin-secreting pituitary tumor, suggestive of the multiple endocrine neoplasia (MEN) I syndrome [2].
• The extent and location of gastrinomas, acid secretory studies, and the presence or absence of MEN-I were determined and correlated with the results of the gastrin response to standard meal provocative testing [3].
• RESULTS: Of the 28 patients with ZES and MEN-I, 11 initially presented with ZES and hyperparathyroidism (HP) and 1 with evidence only for pituitary disease [4].
• Cushing's disease (pituitary ACTH-dependent Cushing's syndrome) has been described in association with the syndrome of multiple endocrine neoplasia type I (MEN-I) [5].

High impact information on Multiple Endocrine Neoplasia Type 1

• 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 [6].
• A family with isolated hyperparathyroidism segregating a missense MEN1 mutation and showing loss of the wild-type alleles in the parathyroid tumors [7].
• Mutations of the MEN1 gene, encoding the tumor suppressor menin, predispose individuals to the cancer syndrome multiple endocrine neoplasia type 1, characterized by the development of tumors of the endocrine pancreas and anterior pituitary and parathyroid glands [8].
• The observation that atropine inhibits serum PP levels in MEN I patients with endocrine pancreatic tumors throws doubt on the clinical usefulness of an atropine suppression test for PP in the diagnosis of pancreatic endocrine tumors [9].
• In 5 other patients with evidence of gastrinoma from MEN I families serum PP levels were normal [9].

Chemical compound and disease context of Multiple Endocrine Neoplasia Type 1

• Intravenous administration of 1 mg atropine to all 19 affected members of MEN I families and to 8 normal control subjects inhibited serum PP in all of them [9].
• Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin [10].
• Comparison of K. oxytoca beta-lactamases with plasmid-mediated extended-spectrum beta-lactamases MEN-1 and TOHO-1 implied that the threonine at position 168 present in OXY-2 beta-lactamase instead of the alanine in OXY-1 could be responsible for its modified substrate hydrolysis [11].
• Plasma TG change over 8 h was determined following a liquid fatty meal in 14 male habitual runners (R) and 13 physically inactive men (I) after 3 weeks of alcohol abstinence and 3 weeks of drinking approximately 41 g (1.44 oz) of ethanol per day [12].
• H2-antagonist therapy should be the initial treatment of choice in patients with MEN I who have ZES [13].

Biological context of Multiple Endocrine Neoplasia Type 1

• A mouse model of MEN1 deficiency causes a phenotype that includes parathyroid hypercellularity albeit unaccompanied by biochemical hyperparathyroidism, and additional mouse models in which menin deficiency is targeted to the parathyroids will likely provide additional important insights [14].
• Toho-1 was about 83% homologous to the beta-lactamase mediated by the chromosome of K. oxytoca D488 and the beta-lactamase mediated by the plasmid of E. coli MEN-1 [15].
• Dexamethasone in resting and exercising men. I. Effects on bioenergetics, minerals, and related hormones [16].
• Loss of heterozygosity at the MEN I locus was found in five of 26 aldosterone-producing tumours from our series (by Japanese collaborators) [17].
• Germline mutations of the MEN1 gene have been identified as the causative genetic defect of multiple endocrine neoplasia type I (MEN-I), an autosomal dominantly inherited condition [18].

Anatomical context of Multiple Endocrine Neoplasia Type 1

• No patient with ZES and MEN I was cured of ZES despite the fact that islet cell tumor was removed from the region of the gastrin gradient in five of six patients [19].
• A brother was found to suffer from peptic ulcer disease caused by hyperparathyroidism and, during screening for other organ involvement associated with the MEN I syndrome, two tumors were found, one (4 cm) in the pancreatic tail region and one in the right adrenal gland [20].

Gene context of Multiple Endocrine Neoplasia Type 1

• Both beta-lactamases are distantly related to other plasmidic class A enzymes (homology to TEM-1 is 38.1% for CTX-M-1/MEN-1 and 36.5% for CTX-M-2); the closest relationship was with the chromosomal beta-lactamase of Klebsiella oxytoca E23004 (homologies of 74.5% for CTX-M-1/MEN-1 and 77.9% for CTX-M-2) [21].
• Studies with the markers D11S480, PYGM, D11S449, and D11S987 in 13 patients (12 of whom were from our group of 16) revealed 4 losses of heterozygosity on D11 S480 on 11q13, but the deletion did not affect the MEN I gene in any case [22].
• The prevalence of GHRH in MEN-I tumours remains to be established [23].
• Thus, mutations in the coding segments of the HNP36 gene are not the cause of the MEN I syndrome [24].
• We conclude that, in comparison with pituitary adenomas occurring in the general population, those occurring in association with MEN-I are (1) more often endocrinologically functional, (2) more frequently GH- or PRL-producing, and (3) clinicopathologically similar in terms of the subjects age and sex as well as of tumor size and invasiveness [25].

Analytical, diagnostic and therapeutic context of Multiple Endocrine Neoplasia Type 1

• It was concluded that hypercalcemia due to hyperparathyroidism in MEN-I syndrome patients should be managed by a resection of four glands and transplantation of one half gland into the forearm because none of the patients has shown evidence of a recurrence, and serum calcium levels have been normal [26].
• A patient with thymic carcinoid and MEN-I was treated with surgical resection and postoperative radiation therapy, which was later followed by subtotal parathyroidectomy for hyperparathyroidism [27].

References