Factors Predicting Outcome of Total Thyroidectomy in Young Patients with Multiple Endocrine Neoplasia Type 2: A Nationwide Long‐Term Follow‐up Study

Schreinemakers, Jennifer M. J.; Vriens, Menno R.; Valk, Gerlof D.; Groot, Jan-Willem B de; Plukker, John; Bax, Klaas N M A; Hamming, Jaap F.; Luijt, Rob B. van der; Aronson, Daniël C.; Rinkes, Inne H.M. Borel

doi:10.1007/s00268-009-0370-2

Cited by 35 publications

(30 citation statements)

References 30 publications

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“…Notably, to our knowledge, this is the first time that a study has shown this result. Few studies examined the long-term outcome after thyroidectomy in MEN2A patients (19,20,21,22); moreover, only one of them (21) analysed differences in the long-term outcome between the different variants of codon 634 mutations, and that study did not find any differences. This previous study had analysed a smaller number of patients than our investigation, and patients were below the age of 20 years.…”

Section: Discussionmentioning

confidence: 99%

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

Valdés

Navarro

Mesa

et al. 2015

European Journal of Endocrinology

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Objective: Specific germline mutations in the RET proto-oncogene are correlated with clinical features in multiple endocrine neoplasia type 2A (MEN2A); however, data are scarce regarding differences in clinical profiles dependent on the type of nucleotide and amino acid substitution at the same codon. We aimed to analyse differences in clinical risk profiles and outcomes among different amino acids encoded by codon 634. Design: The study was retrospective and multicentric. Methods: We collected data included in the Spanish Online National Database from patients with MEN2A carrying a RET proto-oncogene mutation on codon 634. The mean follow-up time was 7.6G6.9 years (1-32). Results: Patients (nZ173) from 49 unrelated families were C634Y carriers, and 26 patients from eight different families had C634R mutation. We found higher penetrance of medullary thyroid carcinoma, phaeochromocytoma and hyperparathyroidism (P!0.001, PZ0.007 and P!0.001 respectively) in C634R carriers than in C634Y carriers. The Kaplan-Meier estimate of cumulative lymph node and distant metastases rates showed that these events occurred earlier in patients harbouring the C634R mutation (P!0.001). A multivariate adjusted Cox regression analysis indicated that the C634R mutation was an independent factor for persistent/recurrent disease (hazard ratio, 3.17; 95% CI: 1.66-6.03; P!0.001). Conclusions: 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.

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Section: Discussionmentioning

confidence: 99%

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

Valdés

Navarro

Mesa

et al. 2015

European Journal of Endocrinology

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“…In 2010, Schreinemakers et al conducted a case-control study to identify prognostic factors associated with recurrent MTC. 79 A total of 93 MEN2 patients were identified as RET-mutation carriers who underwent total thyroidectomy before 20 years of age. Disease-free patients were compared to those with recurrent disease.…”

Section: Cancermentioning

confidence: 99%

RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma

Krampitz

Norton

2014

Cancer

114

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The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto-oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at-risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto-oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto-oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2. Cancer 2014;120:1920-31.

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“…Similarly, Sanso et al [9] reported a case of MTC discovered in a 17-month-old patient with a codon 634 mutation. In Schreinemakers et al’s [10] publication which included 62 patients with the mutation, the earliest age of MTC was 1.25 years.…”

Section: Discussionmentioning

confidence: 99%

Bilateral Medullary Thyroid Carcinoma in a 3-Year-Old Female Patient with Multiple Endocrine Neoplasia 2A Syndrome Undergoing Prophylactic Thyroidectomy: Should Current Guidelines Be Revised?

et al. 2018

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Background: Multiple endocrine neoplasia (MEN) 2A is an autosomal dominant disorder that results from a mutation in the RET proto-oncogene on chromosome 10. Almost all of the affected patients develop medullary thyroid carcinoma (MTC). The American Thyroid Association recommends prophylactic thyroidectomy in MEN 2A pediatric patients, with the age of the recommended thyroidectomy varying according to the codon mutation present. Objectives: This report questions the reliability of the currently placed guidelines and whether the age threshold for prophylactic thyroidectomy in patients with known codon 634 mutations should be lowered, in parallel with an earlier evaluation of calcitonin levels in the serum. Methods: We report the preoperative diagnosis as well as operative and postoperative course of a 3-year-old female patient with MEN 2A (codon 634 mutation) who underwent prophylactic thyroidectomy. The postoperative histopathologic findings are presented and discussed. Results: Despite the prophylactic nature of the operation, in parallel with a borderline calcitonin increase in the serum, bilateral MTC was discovered on pathology. Conclusion: It is likely that the current guidelines should be revised to recommend calcitonin screening and prophylactic thyroidectomy at an earlier age for MEN 2A patients with known codon 634 mutations.

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Factors Predicting Outcome of Total Thyroidectomy in Young Patients with Multiple Endocrine Neoplasia Type 2: A Nationwide Long‐Term Follow‐up Study

Cited by 35 publications

References 30 publications

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

RET Cys634Arg mutation confers a more aggressive multiple endocrine neoplasia type 2A phenotype than Cys634Tyr mutation

RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma

Bilateral Medullary Thyroid Carcinoma in a 3-Year-Old Female Patient with Multiple Endocrine Neoplasia 2A Syndrome Undergoing Prophylactic Thyroidectomy: Should Current Guidelines Be Revised?

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