Impact of RET Screening on the Management of Multiple Endocrine Neoplasia Type 2A: 10 Years Experience and Follow-up in Three Families

2021 ◽  
Vol 21 ◽  
Author(s):  
Yue-Ping Wang ◽  
Fei-Ping Li ◽  
Hui-Hong Wang ◽  
Xu-Dong Fang ◽  
Zai-Sheng Zhu ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Term Outcome ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Younger Age

Background: Multiple endocrine neoplasia type 2A (MEN 2A) is mainly caused by germline RET codon C634 mutation and is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO), and hyperparathyroidism (HPTH). The early diagnosis and initial normative treatment are helpful for the long-term outcome of MEN2A. Methods: Three index cases and their 29 relatives from three families with MEN2A were included in this study. Genetic screening was performed on all participants. Demographic, clinical profiles, tumor histopathologic features, and follow-up records were systematically analyzed. Results: In total, RET C634Y mutation was identified in 10 individuals (10/32, 31.3%). Among them, 5 presented with MTC symptoms, whereas the other 5 did not show apparent clinical manifestation, and all were subjected to thyroidectomy with varying neck dissection. Compared to individuals in the former, the latter benefited greatly from RET screening with significantly younger age at diagnosis of MTC and surgery (18.1 ± 13.8 years vs. 39.0 ± 14.1 years, P =0.045), and less-aggressive MTC behavior (size: 0.74 vs. 2.82 cm, P =0.026; LN+/resected: 20.0% vs. 100.0%, P =0.048) and also lower recurrence rate of MTC (20.0% vs. 100.0%, P =0.048). The PHEO was identified in 6 of the 10 carriers (60.0%), and all had undergone adrenal-sparing surgery. During the 10 years of follow-up, one (16.7%) developed recurrence of PHEO. Conclusion: Integrated RET screening, serum calcitonin, and plasma metanephrine/normetanephrine levels can facilitate the early diagnosis and standardized MTC/PHEO surgery to improve the prognosis of MEN2A. Laparoscopic adrenal-sparing surgery prior to the bilateral total thyroidectomy is a preferred surgical approach for PHEO.

scholarly journals Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

2014 ◽  
Vol 142 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Maja Jesic ◽  
Milina Tancic-Gajic ◽  
Milos Jesic ◽  
Vladan Zivaljevic ◽  
Silvija Sajic ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Prophylactic Thyroidectomy ◽  
Urinary Catecholamines ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy?s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

Molecular diagnosis and treatment of multiple endocrine neoplasia type 2B in Ethnic Han Chinese

2020 ◽  
Vol 20 ◽  
Author(s):  
Zhe-Wei Zhang ◽  
Xiao Guo ◽  
Xiao-Ping Qi
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Histopathological Examination ◽  
Diagnosis And Treatment ◽  
De Novo Mutation ◽  
Neck Lymph Node ◽  
Serum Calcitonin ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2B

Background: Multiple endocrine neoplasia type 2B (MEN 2B) is mainly caused by M918T RET germline mutation, and characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (PHEO) and non-endocrine features. However, the diagnosis and treatment are usually delayed. Materials & Methods: This study reports 5 Chinese pedigrees with 5 individuals harboring germline RET-M918T, and systematically reviewed previous Chinese literatures. Results: All 5 patients initially presented MTC, but none had biochemically cured postoperatively. 2 also presented bilateral PHEO after adrenal-sparing surgery, 1 needed steroid replacement. Further, totally 32 MEN 2B patients from literatures were clustered with 28 available for analysis. 26 (92.8%) were diagnosed by endocrine-related symptoms; the remaining 2 (7.2%) due to RET testing and oral symptoms respectively. 25 patients underwent thyroidectomy with/without neck lymph node dissection at mean age of (23.3 ± 10.4) years. Histopathological examination revealed MTC (100%). Of them, 17 had definite TNM stage, with 1 in stage Ⅲ and others in Ⅳ. Other information of MEN 2B-related symptoms included penetrance of PHEO (60.7%), constipation (32.1%), Hirschsprung disease (25%), alacrima (17.8%), mucosal ganglioneuroma (96.4%) and marfanoid habitus (71.4%). 19 patients were verified harboring RET-M918T (c.2753T>C), of whom 15 (78.9%) were de novo mutation. The other 9 were clinically diagnosed as MEN 2B. Discussion & Conclusion : The initial diagnosis of MEN 2B is relatively later, and diagnosed by non-endocrine components is extremely lower. Recognition of MEN 2B and its non-endocrine-related components is still the utmost requirement for a Chinese physician. Combined RET screening and serum calcitonin detection can facilitate early diagnosis.

LONG-TERM FOLLOW-UP OF A KINDRED WITH MULTIPLE ENDOCRINE NEOPLASIA TYPE IIA

1989 ◽  
Vol 59 (9) ◽  
pp. 683-689 ◽  
Author(s):  
StephenR. Munn ◽  
JonA. Van Heerden ◽  
GlenW. Sizemore ◽  
J. Aidan Carney ◽  
Edward Paloyan ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Long Term Follow Up

Pituitary adenoma in patients with multiple endocrine neoplasia type 1 – a cohort study

2021 ◽  
Author(s):  
Maelle Le Bras ◽  
Hélène Leclerc ◽  
Olivia Rousseau ◽  
Pierre Goudet ◽  
Thomas Cuny ◽  
...  
Keyword(s):  
Cohort Study ◽  
Pituitary Adenoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Tumour Progression ◽  
Standard Of Care ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Objective: Pituitary adenoma (PA) is one of the three major components of multiple endocrine neoplasia type 1 (MEN1). Recent studies have suggested that MEN1-associated PAs are less aggressive than initially estimated. We propose an analysis of the outcome of PAs with standard of care treatment in a nationwide cohort of MEN1 patients. Design: Retrospective observational nationwide cohort study using the MEN1 patient registry from the French Group of Endocrine Tumours (GTE). Methods: The GTE database population consists of 1,435 patients with MEN1. This analysis focused on 551 patients recruited after 2000 with at least 3 years of follow-up. The study outcome was tumour progression of PA defined by an increase in Hardy classification (HC) during follow-up according to referring physician regular reports. Results: Among 551 MEN1 patients (index and related), 202 (36.7%) had PA, with 114 (56.4%) diagnosed by MEN1-related screening. PAs were defined according to HC as microadenoma (grade I) in 117 cases (57.9%), macroadenoma in 59 (29.2%) with 20 HC grade II and 39 HC grade III-IV and unspecified in 26 (12.8%). They were prolactinomas in 92 cases (45.5%) and non-secreting in 73 (36.1%). After a median follow-up of 3 years among the 137 patients with HC grades I-II, 4 patients (2.9%) presented tumour progression. Conclusion: PAs in patients with MEN1 are less aggressive than previously thought. Tumour progression is rare with standard of care monitoring and treatment, especially in related patients who mostly present non-secreting microadenoma. MRI monitoring for asymptomatic MEN1 patients should be reduced accordingly.

Sign in / Sign up

Export Citation Format

Share Document