Carcinoma of two parathyroid glands caused by a novel MEN1 gene mutation - a rare feature of the MEN 1 syndrome.

Multiple endocrine neoplasia type 1 (MEN 1) is a rare syndrome inherited in an autosomal dominant pattern, characterized by combinations of tumors of the parathyroid glands, pituitary gland, and pancreatic islet cells and more rare tumors of endocrine organs and nonendocrine tissues. Germline mutations in the MEN1 gene are responsible for the MEN 1 syndrome, leading to an inactive form of menin protein. Benign lesions of the parathyroid glands are characteristic in patients with the MEN 1 syndrome; however, patients can develop parathyroid carcinomas very rarely. This report presents a clinical case of the MEN 1 syndrome: a 39-year-old woman underwent surgery for carcinoma of two parathyroid glands as well as was treated for pituitary prolactinoma, which caused infertility, and malignant insulinoma; the patient had multiple subcutaneous lipomas as well. Genetic analysis revealed a novel germline mutation in the MEN1 gene - a nucleotide insertion at codon 43 in exon 2 (c.129insA), which caused the occurrence of the MEN1 syndrome. The clinical case of the MEN 1 syndrome presented here is relevant in gathering the data on etiopathogenesis of not only MEN 1 syndrome, but an extremely rare pathology - parathyroid carcinoma - as well.

[Multiple endocrine neoplasia type 2A]. / Dauginiu endokrininiu naviku sindromo 2A tipas.

Multiple endocrine neoplasia (MEN) type 2A, or Sipple syndrome, is a rare autosomal dominantly inherited syndrome, which is characterized as combination of medullary thyroid carcinoma, pheochromocytoma, primary hyperparathyroidism, sometimes with rarer inherited disorders like Hirschsprung disease and cutaneous lichen amyloidosis. Syndrome is caused by germinative mutations in c-ret protooncogene, which are typical for different MEN 2 syndromes. We report a clinical case of MEN 2A. A 43-year-old female patient was operated on for pheochromocytoma 7 years after diagnosis and treatment of spread medullary thyroid carcinoma. This is the most common combination of MEN 2A tumors. Diagnosis was based upon clinical data, tumors combinations and analysis of inherited endocrine pathology in first-line relatives. This syndrome has already been diagnosed in Lithuania, but in the last decade after determining the genetic basis of MEN 2 and applying modern genetic examinations in clinical praxis, the strategy of diagnostics and prophylaxis of this syndrome has changed and survival prognosis for patients with this syndrome has improved. Conception of pathogenesis and clinical features of MEN 2A syndrome, genetic selection of inheritors of this syndrome is one more step in early cancer diagnosis, which allows to use cancer prevention measures in time, to apply effective treatment and improve patients' prognosis. Reporting this clinical case of MEN 2A we aimed to pay attention of general practitioners to this rare, but in Lithuania diagnosed too, syndrome and its clinic, diagnostic, and treatment features.

[Multiple endocrine neoplasia syndromes. Type 2]. / Dauginiu endokrininiu naviku sindromai. Antrasis tipas.

The second type of multiple endocrine neoplasia syndromes can be described as rare syndromes, heritable in autosomal dominant manner and linking medullary thyroid carcinoma to different tumors of endocrine organ system and endocrinopathies. This syndrome is divided into multiple endocrine neoplasia syndrome type 2A (MEN 2A), characterized with combination of medullary thyroid carcinoma, pheochromocytoma and primary hyperparathyroidism; type 2B (MEN 2B), characterized with combination of medullary thyroid carcinoma, pheochromocytoma, marfanoid habitus and ganglioneuromatosis, and familial medullary thyroid carcinoma syndrome, characterized with the only indication, which is hereditary medullary thyroid carcinoma. Though type 2 multiple endocrine neoplasia syndrome has been known since 1961, yet, the cause of the syndrome, which is germline mutations of c-ret protooncogene, was detected just a decade ago and syndrome pathogenesis with its characterized endocrine neoplasia carcinogenesis machinery were detected. Implementation of progressive genetic researches in clinical practice enabled precise diagnosis of multiple endocrine neoplasia syndrome and its subtypes not only for ill patients but also for healthy syndrome inheritors, e.g. relatives of the sick. Stated genotype link to phenotype helps to prognosticate possible combinations of endocrine neoplasia and endocrinopathies, and to choose purposeful patient observation. Genetic screening of the inheritors of multiple endocrine neoplasia type 2 syndrome enabled purposeful researches and observations of patients with a huge risk of uprising endocrine neoplasia, it also enabled application of effective prophylaxis methods, avoidance or early diagnostic of malignant tumors and life prognosis improvement for patients with malignant tumors while practicing well-timed treatment adaptation. This literature review contains the newest data on multiple endocrine neoplasia syndrome type 2 and its pathogenesis, diagnostics, patient observation, endocrine cancer prophylaxis and methods of treatment, which are characteristic for syndrome and which are being chosen according to biochemical endocrine neoplasia symptoms and genetic diagnosis.

[Multiple endocrine neoplasia syndroms. Type 1]. / Dauginiu endokrininiu naviku sindromai. Pirmas tipas.

Multiple endocrine neoplasia (MEN) type 1 syndrome or Wermer syndrome is a classical malignant neoplasia syndrome, inherited in the autosomal dominant pattern, when hyperplastic and/or neoplastic injury develops synchronously or metachronously in the cells of the parathyroid gland, pancreas islets, hypophysis, and rarer in other neuroendocrine organs. The syndrome develops when germinative MEN 1--neoplasia suppression gene inactivation mutations occurs. More than 95 percent of patients have this MEN 1 gene mutation, when the penetration of mutation is almost 100 percent. An early stage of this syndrome is hyperfunction in organs, with the syndromes of hormone excess, later benign and/or malign neoplasia develops, this mostly determines the prognosis for the patient. The risk of this syndrome developing should be estimated for all the patients diagnosed with endocrine organ hyperplasia, which determines hyperfunction, or endocrine organs neoplasia. For patients with multiple endocrine neoplasia type 1 syndrome, endocrine neoplasia develops earlier than in sporadic cases; multifocality is typical for them. Multifocality of neoplasia, typical combinations of injuries and anamnesis of the family helps to diagnose the syndrome. Diagnosis is confirmed through genetical analysis, which is also important in determining the inheritors of mutations, potential patients. After genetically diagnosing multiple endocrine neoplasia type 1 syndrome, it is not enough to analyze and look after patients with malignant neoplasia, or to make early diagnosis on pre-neoplasic disease and neoplasia, or to apply means of prevention and start well-timed treatment, but also to diagnose this syndrome for the patient's relatives, and to determine their risk of getting cancer. This opens new possibilities in early diagnostics and prevention of malignant neoplasia. The main purpose of this literature review is to introduce medical-practitioners to the newest theories of type 1 multiple endocrine neoplasia syndrome pathogenesis, clinical peculiarities, methods of diagnostics and treatment.