Multiple Endocrine Neoplasia Type 2a (MEN 2)

A form of multiple endocrine neoplasia characterized by the presence of medullary carcinoma (CARCINOMA, MEDULLARY) of the THYROID GLAND, and usually with the co-occurrence of PHEOCHROMOCYTOMA, producing CALCITONIN and ADRENALINE, respectively. Less frequently, it can occur with hyperplasia or adenoma of the PARATHYROID GLANDS. This disease is due to gain-of-function mutations of the MEN2 gene on CHROMOSOME 10 (Locus: 10q11.2), also known as the RET proto-oncogene that encodes a RECEPTOR PROTEIN-TYROSINE KINASE. It is an autosomal dominant inherited disease.

Also Known As:

Networked: 1037 relevant articles (17 outcomes, 78 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Pheochromocytoma
2.	Neoplasms (Cancer)
3.	Multiple Endocrine Neoplasia Type 2b (MEN 3)
4.	Multiple Endocrine Neoplasia Type 2a (MEN 2)
5.	Multiple Endocrine Neoplasia (Multiple Endocrine Adenomatosis)

Experts

1.	Pacak, Karel: 14 articles (04/2015 - 02/2003)
2.	Takahashi, M: 10 articles (04/2014 - 01/2000)
3.	Eisenhofer, Graeme: 10 articles (05/2012 - 08/2005)
4.	Iwashita, T: 8 articles (04/2014 - 01/2000)
5.	Santoro, Massimo: 8 articles (08/2013 - 06/2002)
6.	Takahashi, Masahide: 8 articles (05/2010 - 04/2002)
7.	Dralle, Henning: 7 articles (01/2012 - 12/2002)
8.	Linehan, W Marston: 7 articles (03/2011 - 06/2005)
9.	Pacak, K: 7 articles (04/2009 - 05/2001)
10.	Wells, Samuel A: 6 articles (10/2015 - 09/2005)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Multiple Endocrine Neoplasia Type 2a:

1.	DNA (Deoxyribonucleic Acid)IBA 03/01/2013 - "Our case study confirms that integrated DNA-based/biochemical screening is crucial for early diagnosis of MEN2A and is helpful in the screening of their relatives. " 07/01/2001 - "To study RET mutations in 8 families with MEN 2. RET mutations were screened in peripheral blood DNA from 18 patients and 87 high risk carriers belonging to 8 MEN 2 families and 52 sporadic MTC. " 12/01/1995 - "This study presents our experience with direct presymptomatic DNA screening in MEN 2 and FMTC kindreds. " 03/01/2013 - "A Han Chinese pedigree with MEN2A was investigated following confirmation of the proband's diagnosis by pathological findings and DNA/biochemical screening. " 11/01/2008 - "Nearly 100% of MEN2A are associated with germ line mutation of the RET proto-oncogene (RET), and DNA-based RET genotype analysis is now considered essential for earlier diagnosis. "
2.	Pentagastrin (Peptavlon)FDA Link 11/01/2007 - "Pentagastrin stimulation test was helpful for the diagnosis and follow-up after operative treatment of MEN2A." 04/01/2003 - "We report the results of molecular genetic investigations, the pentagastrin stimulation test, pre- and postoperative staging, and histologic examinations of four children who had a positive family history for MEN 2A. " 07/01/2000 - "The authors discuss the value of pentagastrin test and genetic testing in the early diagnosis of MTC associated with MEN 2A syndrome." 02/01/1996 - "Sequential and single pentagastrin stimulation test data were collected following the identification of RET mutation positive and RET mutation negative members of families with MEN 2A or FMTC. " 02/01/1996 - "The identification of false positive responses to the pentagastrin stimulation test in RET mutation negative members of MEN 2A families."
3.	Calcitonin (Calcitonin, Eel)FDA LinkGeneric 11/01/1999 - "Seventy-one MEN 2/FMTC gene carriers, collected through the national register of the French Calcitonin Tumours Study Group, were evaluated. " 07/05/2009 - "48 cases of MEN2a had thyroid masses with elevated calcitonin levels. " 11/01/1999 - "Determination of calcitonin forms an integral part of the management of MEN 2 gene carriers. " 01/01/1998 - "Mice carrying a MEN 2A allele of RET under the control of the CGRP/calcitonin promoter develop bilateral and multifocal MTC, morphologically and biologically similar to human MTC." 01/01/1997 - "This relationship has been unknown until the present time, whereas it can be of great clinical significance, in part because of the changes in serum calcitonin levels, in part for screening out the MEN IIa type and working out the operating strategy."
4.	Codon (Codons)IBA 09/01/2001 - "We conclude that screening for mutations in these codons is effective in families fulfilling the strict clinical criteria of MEN2A or FMTC." 10/01/2004 - "Taking other studies into account, 77% (10/13) of Korean families with MEN 2A, including 7 other families in three reports from Korea, had RET mutations in codon 634 (5 families, C634Y; 4 families, C634R; 1 family, C634W), and 23% (3/13) had RET mutations in codon 618 (2 families, C618R; 1 family, C618S). " 01/15/2002 - "Molecular studies showed a mutation at codon 634, exon 11 in all MEN 2A patients. " 09/01/2001 - "In our study, mutations in the above codons were detected in all of the 14 clinically MEN2A and FMTC families. " 03/01/2015 - "Our results suggest that there could be clinical differences caused by different amino acid substitutions at codon 634; specifically, the C634R mutation was associated with a more aggressive MEN2A phenotype than the C634Y mutation."
5.	Factor IX (PTC)FDA LinkGeneric 11/01/2015 - "More studies are needed to correlate genetics and histology, and even for assessing PTC as only manifestation of MEN 2." 11/01/2015 - "Few data are available about PTC in MEN 2, and without C-cell pathology is even less common. " 08/01/2004 - "We tested on thyroid follicular cells the transforming activity of RET(C634S), RET(K603Q), another mutant identified in a kindred with both PTC and MTC, RET(C634R) a commonly isolated allele in MEN2A, RET(M918T) responsible for MEN2B and also identified in kindreds with both PTC and MTC, and RET/PTC1 the rearranged oncogene that characterizes bona fide PTC in patients without MTC. " 10/01/2000 - "Moreover, regardless of the nature of the underlying activating mutation, the concomitant phosphorylation of Y1015 and Y1062 is a common feature of the various oncogenic RET products (MEN2A, MEN2B, and PTC). " 03/01/2000 - "It is clear that RET is responsible for MEN 2A, MEN 2B, FMTC, and PTC. "
6.	Insulin (Novolin)FDA Link 07/01/1996 - "Furthermore, insulin suppression of FFAs improved with age in men (2% per decade, P < 0.0001) but not in women. " 01/01/1996 - "In conclusion, insulin-mediated MSNA: 1) is neither a response to nor a cause of the vasodilation observed in insulin sensitive men, 2) has no net pressor effect even in the most insulin resistant men in whom insulin-mediated vasodilation was impaired. " 05/01/1992 - "We investigated the sensitivity to insulin with a hyperinsulinemic (approximately 719 pM [approximately 100 microU/ml]) euglycemic clamp in two groups of normotensive nonproteinuric IDDM patients; 12 (10 men, 2 women) had high Na+/Li+ CT activity (mean 0.47, range 0.42-0.68 mmol/L red blood cells [RBC]/h, group 1) and 12 (9 men, 3 women) had normal Na+/Li+ CT activity (mean 0.24, range 0.12-0.31 mmol/L RBC/h, group 2). " 05/01/1990 - "We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women." 06/01/2000 - "It is concluded that (1) the athletes have more adequate compensation for the bed-rest-induced decrement in insulin sensitivity than sedentary men; (2) three-day bed rest diminishes basal sympathetic activity and attenuates sympathoadrenal response to oral glucose; (3) endurance athletes have greater sympathetic inhibition than strength athletes or sedentary men."
7.	SeleniumIBA 01/01/2011 - "an aetiological relationship between selenium exposure and cancer risk in women and men?2. the efficacy of selenium supplementation for cancer prevention in women and men? " 12/01/2014 - "Generally, the results of the current study show the following: (1) hair mercury is associated with serum TG concentration and GGT activity in men, (2) hair selenium content is not related to hair mercury concentration, and (3) mercury-to-selenium ratio correlates with lipid spectrum parameters and GGT activity. "
8.	Granulocyte Colony-Stimulating Factor (G-CSF)IBA 09/01/2012 - "Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. "
9.	Vincristine (Oncovin)FDA LinkGeneric 09/01/2012 - "Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. "
10.	Mitoxantrone (Novantrone)FDA LinkGeneric 09/01/2012 - "Reinduction with: (i) mitoxantrone, etoposide, and cytarabine (MEA); (ii) fludarabine, cytarabine, pegylated-asparaginase plus granulocyte colony-stimulating factor (FLAG-Asp); and (iii) cytarabine, betamethasone, cyclophosphamide, daunorubicin, and vincristine (ABCDV) resulted in complete remission in 6/9 (67%), 10/16 (63%) and 9/21 (43%) of the patients, respectively. "

Therapies and Procedures

1.	Thyroidectomy 01/01/2009 - " multiple endocrine neoplasia type 2 (MEN2), RET mutation analysis is the gold-standard for the recommendation of total preventive thyroidectomy to relatives at risk of harboring a germline RET mutation (50%). " 09/01/2013 - "This study confirms that RET 790 mutation is associated with a non-aggressive form of multiple endocrine neoplasia type 2, as 28% of the patients were followed up without thyroidectomy, 25% had been thyroidectomised with no tumour being detected and even patients with MTC had slow-evolving disease. " 04/01/1998 - "Fifteen patients with MEN II A (aged 4-24 years) who had undergone prophylactic thyroidectomy since 1990 were included in the study. " 12/01/1995 - "The present study evaluated OCT and pentavalent 99mTc-dimercapto-succinic-acid (99mTc-DMSA-V) scintigraphy performed in 13 patients with a histologic diagnosis of MTC and in one with MEN 2A, all of whom had undergone thyroidectomy between 3 months and 15 years before. " 10/01/2015 - "Between 1993 and 2000, we performed preventive thyroidectomies on 50 patients with MEN2A (group A). "
2.	Adrenalectomy 05/01/2014 - "Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study." 04/01/1996 - "The purpose of this study is to review the current status of patients with MEN 2 who underwent adrenalectomy with or without adrenal autotransplantation. " 01/01/2014 - "Currently, there is limited literature on bilateral simultaneous laparoscopic adrenalectomy in MEN 2 syndrome. " 07/23/2013 - "A combination of pedigree examination and RET gene screening may facilitate an early diagnosis and early treatment of asymptomatic PHEO patients in MEN2A.Laparoscopic cortical-sparing adrenalectomy for preserving adrenocortical function is a preferred surgical approach." 01/12/2002 - "Retrospective analysis of 22 all-consecutive laparoscopic adrenalectomies in 21 patients (10 women, 11 men, age 26-70 years, mean 43 years, 11 right, 9 left, one bilateral in MEN IIa syndrome). "
3.	Transplantation (Transplant Recipients) 01/01/2013 - "Ten heart transplant recipients (8 men, 2 women) on CsA-based immunosuppression were enrolled in this prospective single-center pilot study. " 09/01/2003 - "The data of the present study indicate that: 1) ED is still present in many transplanted men; 2) renal transplantation cures ED in only few cases; 3) ED may appear "ex novo" after transplantation." 11/01/1980 - "The recommendations give I. essential rules of international health organisations and II. Medical-ethic guidelines regarding different questions: 1. research examinations on men 2. euthanasia 3. transplantation 4. artificial insemination 5. sterilisation, especially the operative sterilisation of mentally handicapped persons, without acceptation of the so-called forced sterilisation 6. medical-ethical committees. " 01/01/1989 - "An experimental animal model with adrenal cortex transplantation was developed to study adrenal cortex replacement therapy in patients with multiple endocrine neoplasia type 2 who have had bilateral adrenalectomy for pheochromocytomas. " 10/01/2011 - "We present the case of a 37-year-old patient diagnosed with multiple endocrine neoplasia type 2A (MEN 2A) syndrome, as confirmed by genetic tests, who underwent the transplantation of a kidney from a cadaveric donor. "
4.	Drug Therapy (Chemotherapy) 03/01/2007 - "Lack of applicable safety data has effected an ease in federal restriction on the inclusion of women in clinical trials, particularly because: (1) they consume more prescription and over-the-counter medications than do men; (2) most require some type of drug therapy during pregnancy; and (3) many drugs that have been withdrawn from the market had higher health risks for women. " 08/01/2013 - "From January 2009 to May 2010, neoadjuvant chemotherapy was indicated in 27 patients with NSCLC (25 men, 2 women). " 01/01/2009 - "A total of 14 (18)F-FDG PET scans (8 for initial staging, 6 for evaluation of response to chemotherapy and radiation therapy) were performed in 8 patients (6 men, 2 women). " 01/01/2015 - "Despite knowing the oncogene responsible for MEN2A, MTC, like most tumors of neural crest origin, remains largely resistant to chemotherapy. " 08/17/1990 - "14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. "
5.	Kidney Transplantation 10/01/2011 - "Successful kidney transplantation in a patient with multiple endocrine neoplasia type 2A syndrome: case study." 09/01/2003 - "The data of the present study indicate that: 1) ED is still present in many transplanted men; 2) renal transplantation cures ED in only few cases; 3) ED may appear "ex novo" after transplantation."