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The Journal of International Medical... Jan 2021Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant genetic disease. MEN1 with multiple endocrine adenomatosis complicated by multiple endocrine...
BACKGROUND
Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant genetic disease. MEN1 with multiple endocrine adenomatosis complicated by multiple endocrine tumors is often misdiagnosed or missed. Herein, we describe the first reported case of refractory hypoglycemia and liver and lung metastases in a patient with MEN1.Case presentation: A 40-year-old man presented with a 3-month history of intermittent palpitations, fatigue, and sweating. The patient had a history of prolactinoma resection and refractory hypoglycemia 2 years earlier. Analyses of blood samples showed a decrease in random and fasting blood glucose and an increase in prolactin (PRL). Computed tomography (CT) and magnetic resonance imaging scans revealed two substantial masses in the pancreas and large masses in the liver and lung. Positron emission tomography-CT images showed hypermetabolic masses in the pancreatic body and tail. The liver and lung lesions were also hypermetabolic. The pancreatic lesion was surgically removed, and pathology confirmed that the mass was MEN1. The liver and lung masses were confirmed as metastatic tumors.
CONCLUSION
If clinicians better understand MEN1, they can obtain a detailed patient and family history during the initial visit, allowing earlier diagnosis and intervention and improved prognosis.
Topics: Adult; Humans; Hypoglycemia; Liver Neoplasms; Lung; Male; Multiple Endocrine Neoplasia Type 1; Pancreatic Neoplasms; Pituitary Neoplasms
PubMed: 33435778
DOI: 10.1177/0300060520961682 -
The Journal of Clinical Endocrinology... Jan 2019Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early-onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of pheochromocytoma...
CONTEXT
Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early-onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of pheochromocytoma (PHEO) development. The literature on PHEO in patients with MEN2B is limited with most data being reported from adult studies that primarily address MEN2A.
OBJECTIVE
The aim of the current study is to describe PHEO development in a cohort of pediatric patients with MEN2B.
DESIGN
Retrospective chart review of patients with MEN2B evaluated at the National Institutes of Health in the period between July 2007 and February 2018.
RESULTS
A total of 38 patients were identified (21 males and 17 females). Mean age at MEN2B diagnosis was 10.6 ± 3.9 years. Eight patients (21%) developed PHEO in the course of follow-up to date, all of whom were sporadic cases with the classic M918T RET mutation. PHEO was diagnosed based on biochemical and/or imaging screening studies in five patients, whereas three patients presented with symptoms of excess catecholamines. PHEO was diagnosed at a mean age 15.2 ± 4.6 (range, 10 to 25) years and 4.0 ± 3.3 years after MEN2B diagnosis. Only one patient was diagnosed with PHEO as the initial manifestation of MEN2B after she presented with hypertension and secondary amenorrhea.
CONCLUSION
Undiagnosed PHEO can be associated with substantial morbidity. Current American Thyroid Association guidelines recommend PHEO screening starting at age 11 for the high-/highest risk group. The youngest patient diagnosed with PHEO in our cohort was an asymptomatic 10-year-old, suggesting that PHEO development may begin before the screening-recommended age of 11, though remains clinically undetectable and thus the current screening guidelines seem appropriate.
Topics: Adolescent; Adrenal Gland Neoplasms; Adult; Age of Onset; Catecholamines; Child; Cohort Studies; Disease Progression; Female; Follow-Up Studies; Humans; Male; Mass Screening; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Pheochromocytoma; Retrospective Studies; Young Adult
PubMed: 30113649
DOI: 10.1210/jc.2018-00705 -
Clinics (Sao Paulo, Brazil) 2012Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine... (Review)
Review
Multiple endocrine neoplasia (MEN) types 1 and 2 are genetic diseases that are inherited as autosomal traits. The major clinical manifestations of multiple endocrine neoplasia type 1 include the so-called "3 P's": parathyroid, pituitary, and pancreatic tumors, including gastroenteroneuroendocrine tumors. Genetic testing can be performed on patients and the potential carriers of the menin gene mutation, but the genotype-phenotype correlation in multiple endocrine neoplasia type 1 is less straightforward than multiple endocrine neoplasia type 2. Most likely, the main advantage of genetic testing in MEN1 is to exclude from further studies those who are negative for the genetic mutation if they belong to a family with a known history of MEN1. In Chile, we started with rearranged during transfection proto-oncogene genetic testing (MEN2) 15 years ago. We carried out a prophylactic total thyroidectomy to prevent medullary thyroid carcinoma in a three-year-old girl who presented with microscopic medullary thyroid carcinoma. More than 90% of the individuals who tested positive using a genetic test achieved a biochemical cure compared with only 27% of patients who receive a clinical diagnosis. Mutations are mainly located in exon 11; the most common is C634W, rather than C634R. Hypertensive crisis was the cause of death in three patients, and extensive distant metastases occurred in nine (including two patients with multiple endocrine neoplasia type 2B) of 14 patients. Earlier recognition of medullary thyroid carcinoma and the other features of the disease, especially pheochromocytoma, will improve the survival rate of patients with multiple endocrine neoplasia.
Topics: Carcinoma, Medullary; Carcinoma, Neuroendocrine; Chile; Female; Genetic Association Studies; Genetic Testing; Humans; Male; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2a; Mutation; Proto-Oncogene Mas; Thyroid Neoplasms; Thyroidectomy
PubMed: 22584699
DOI: 10.6061/clinics/2012(sup01)03 -
Journal of Internal Medicine Jan 2005Each multiple endocrine neoplasia (MEN) syndrome expresses striking features of hormone oversecretion from its own characteristic group of tissues. Additional... (Review)
Review
Each multiple endocrine neoplasia (MEN) syndrome expresses striking features of hormone oversecretion from its own characteristic group of tissues. Additional expressions include non-hormonal tumours in each MEN syndrome and selected cancers in some syndromes. The complexity of its stereotyped features results in difficult management issues that often justify cooperation across multiple specialties. MEN syndromes, though rare, have long received intense study as models for more common diseases. The syndromal nature often with a large pedigree has promoted recent discovery of the main gene that differs for each of the six MEN syndromes. Each mutant gene has been introduced into clinical decision-making and into further clarification of tumorigenesis. This mini-symposium is related to the 9th International Workshop on Multiple Endocrine Neoplasia in June 2004; it consists of six manuscripts. They report new developments in clinical practices and in basic understandings about this rapidly advancing field.
Topics: Genotype; Humans; Hyperparathyroidism; Multiple Endocrine Neoplasia; Mutation; Patient Care Team; Phenotype
PubMed: 15606371
DOI: 10.1111/j.1365-2796.2004.01419.x -
Genetics in Medicine : Official Journal... Sep 2011Multiple endocrine neoplasia type 2 is historically composed of three clinical subtypes, all of which are associated with germline mutations in the RET proto-oncogene.... (Review)
Review
Multiple endocrine neoplasia type 2 is historically composed of three clinical subtypes, all of which are associated with germline mutations in the RET proto-oncogene. Multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and multiple endocrine neoplasia type 2B are collectively associated with a 70-100% risk of medullary thyroid carcinoma by age 70 years. Pheochromocytomas are identified in 50% of individuals with multiple endocrine neoplasia type 2A and multiple endocrine neoplasia type 2B. Furthermore, those with multiple endocrine neoplasia type 2A have a 20-30% risk for primary hyperparathyroidism. Individuals with multiple endocrine neoplasia type 2B often have distinct physical features including mucosal neuromas of the lips and tongue, medullated corneal nerve fibers, ganglioneuromatosis of the gastrointestinal tract, distinctive facies with enlarged lips, and a "Marfanoid" body habitus. Clinical recognition and accurate diagnosis of individuals and families who are at risk of harboring a germline RET mutation is critical for the prevention and management of potentially life-threatening neoplasms. This overview summarizes the clinical description of multiple endocrine neoplasia type 2, diagnosis and testing strategies, management and surveillance, and differential diagnosis for other related syndromes.
Topics: Adrenal Gland Neoplasms; Carcinoma, Medullary; Diagnosis, Differential; Genotype; Humans; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Mutation; Neoplastic Syndromes, Hereditary; Phenotype; Pheochromocytoma; Proto-Oncogene Mas; Thyroid Neoplasms
PubMed: 21552134
DOI: 10.1097/GIM.0b013e318216cc6d -
Journal of Medical Genetics Nov 2000Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome characterised by medullary thyroid carcinoma (MTC), with or without phaeochromocytoma and... (Review)
Review
Multiple endocrine neoplasia type 2 (MEN 2) is an inherited cancer syndrome characterised by medullary thyroid carcinoma (MTC), with or without phaeochromocytoma and hyperparathyroidism. MEN 2 is unusual among cancer syndromes as it is caused by activation of a cellular oncogene, RET. Germline mutations in the gene encoding the RET receptor tyrosine kinase are found in the vast majority of MEN 2 patients and somatic RET mutations are found in a subset of sporadic MTC. Further, there are strong associations of RET mutation genotype and disease phenotype in MEN 2 which have led to predictions of tissue specific requirements and sensitivities to RET activity. Our ability to identify genetically, with high accuracy, subjects with MEN 2 has revolutionised our ability to diagnose, predict, and manage this disease. In the past few years, studies of RET and its normal ligand and downstream interactions and the signalling pathways it activates have clarified our understanding of the roles played by RET in normal cell survival, proliferation, and differentiation, as well as in disease. Here, we review the current knowledge of the normal functions of RET and the effects of mutations of this gene in tumorigenesis and in normal development.
Topics: Carcinoma, Medullary; Drosophila Proteins; Genotype; Humans; Multiple Endocrine Neoplasia; Mutation; Phenotype; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Thyroid Neoplasms
PubMed: 11073534
DOI: 10.1136/jmg.37.11.817 -
Endocrine Journal Sep 2020Autoimmune Addison's disease (AAD) is a rare condition occurring either in isolation or associated with other autoimmune diseases as part of an autoimmune polyglandular...
Autoimmune Addison's disease (AAD) is a rare condition occurring either in isolation or associated with other autoimmune diseases as part of an autoimmune polyglandular syndrome (APS) type 1, 2 or 4. Multiple endocrine neoplasia (MEN) type 1, 2 or 4 is a hereditary autosomal dominant cancer syndrome. Medullary thyroid carcinoma and pheochromocytoma are neoplasms common to MEN-2a and MEN-2b. We describe a unique, complex case of a man resulted affected by both APS-2 and MEN-2a. The patient developed Hashimoto's thyroiditis, diabetes mellitus type 1 and AAD, despite testing negative for adrenal cortex autoantibodies (ACA) and steroid 21-hydroxylase autoantibodies (21-OHAb). Moreover, he had also a family history for MEN-2a and he first developed medullay thyroid cancer, then bilateral pheochromocytoma on the adrenal substrate of an AAD. On adrenal histology we found complete bilateral cortical atrophy in the presence of a lymphocytic infiltration and fibrosis, confirming an ACA and 21-OHAb-negative AAD. This datum is the first documented in a living individual and confirms that the absence of autoantibodies is not incompatible with an autoimmune disease and confirms that AAD is a cell-mediated autoimmune disease limited to the adrenal cortex and sparing medullary. In the light of a literature review concerning the association between APS and MEN, this is the first proven case to be reported in humans. Finally, our findings suggest that adrenal medullary tumor can develop even on an adrenal gland with cortical atrophy due to autoimmune adrenalitis.
Topics: Adrenal Gland Neoplasms; Adult; Humans; Male; Multiple Endocrine Neoplasia; Pedigree; Pheochromocytoma; Polyendocrinopathies, Autoimmune
PubMed: 32475862
DOI: 10.1507/endocrj.EJ20-0099 -
Medicine Jul 2023Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine... (Review)
Review
RATIONALE
Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare.
PATIENT CONCERNS
A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes.
DIAGNOSES
After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases.
INTERVENTIONS
The patient underwent parathyroid tumor resection and metastasis biopsy.
OUTCOMES
The patient received denosumab and sorafenib treatment.
LESSONS
As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment.
Topics: Male; Humans; Adult; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors; Pituitary Neoplasms; Multiple Endocrine Neoplasia; Hyperparathyroidism; Parathyroid Neoplasms; Pancreatic Neoplasms
PubMed: 37478229
DOI: 10.1097/MD.0000000000034350 -
Acta Medica Portuguesa 2007The knowledge of genetics has increased in recent years and has led to important changes in management of hereditary diseases. Multiple endocrine neoplasia is... (Review)
Review
The knowledge of genetics has increased in recent years and has led to important changes in management of hereditary diseases. Multiple endocrine neoplasia is characterized by the occurrence of benign or malign tumours involving two or more endocrine glands and two major forms are recognized: MEN1 and MEN2. All these forms of MEN are inherited as autosomal dominant syndromes. In this article we briefly review the clinic, diagnosis and treatment for the MEN1 and MEN2 and the indications for genetic testing.
Topics: Humans; Multiple Endocrine Neoplasia
PubMed: 17624285
DOI: No ID Found -
Orphanet Journal of Rare Diseases Nov 2006Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or... (Review)
Review
Multiple Endocrine Neoplasia Type 2 (MEN2) is a rare hereditary complex disorder characterized by the presence of medullary thyroid carcinoma (MTC), unilateral or bilateral pheochromocytoma (PHEO) and other hyperplasia and/or neoplasia of different endocrine tissues within a single patient. MEN2 has been reported in approximately 500 to 1000 families worldwide and the prevalence has been estimated at approximately 1:30,000. Two different forms, sporadic and familial, have been described for MEN2. Sporadic form is represented by a case with two of the principal MEN2-related endocrine tumors. The familial form, which is more frequent and with an autosomal pattern of inheritance, consists of a MEN2 case with at least one first degree relative showing one of the characteristic endocrine tumors. Familial medullary thyroid carcinoma (FMTC) is a subtype of MEN2 in which the affected individuals develop only medullary thyroid carcinoma, without other clinical manifestations of MEN2. Predisposition to MEN2 is caused by germline activating mutations of the c-RET proto-oncogene on chromosome 10q11.2. The RET gene encodes a single-pass transmembrane tyrosine kinase that is the receptor for glial-derived neurotrophic growth factors. The combination of clinical and genetic investigations, together with the improved understanding of the molecular and clinical genetics of the syndrome, helps the diagnosis and treatment of patients. Currently, DNA testing makes possible the early detection of asymptomatic gene carriers, allowing to identify and treat the neoplastic lesions at an earlier stage. In particular, the identification of a strong genotype-phenotype correlation in MEN2 syndrome may enable a more individualized treatment for the patients, improving their quality of life. At present, surgical treatment offers the only chance of cure and therefore, early clinical and genetic detection and prophylactic surgery in subjects at risk are the main therapeutic goal.
Topics: Carcinoma, Medullary; Genetic Predisposition to Disease; Genetic Testing; Humans; Multiple Endocrine Neoplasia Type 2a; Mutation; Pheochromocytoma; Proto-Oncogene Mas; Proto-Oncogene Proteins c-ret; Thyroid Neoplasms
PubMed: 17105651
DOI: 10.1186/1750-1172-1-45