Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management

Raue, Friedhelm; Frank‐Raue, Karin

doi:10.14310/horm.2002.1218

Cited by 87 publications

(47 citation statements)

References 23 publications

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“…There is controversy regarding whether the C634R mutation confers a greater risk of developing parathyroid disease (4,7,9,24,25). Our investigation showed a significantly higher HPT prevalence in C634R carriers than in those with the C634Y mutation, despite the fact that more patients above the age of 40 years harboured the C634Y mutation and that the risk of developing HPT increases beyond this age.…”

Section: Discussionmentioning

confidence: 50%

“…Genotype-phenotype correlation has been described between specific codon mutation and the age of onset, penetrance and clinical aggressiveness of MTC (1,2,6,7). Based on these findings, the American Thyroid Association (ATA) Task Force has published management guidelines (8) on the timing and extension of prophylactic thyroidectomy establishing four different risk categories (from A, the lowest, to D, the highest).…”

Section: Introductionmentioning

confidence: 99%

“…Based on these findings, the American Thyroid Association (ATA) Task Force has published management guidelines (8) on the timing and extension of prophylactic thyroidectomy establishing four different risk categories (from A, the lowest, to D, the highest). There is also a different prevalence of PHEO and HPT according to the type of specific codon mutation (7,9,10).…”

Section: Introductionmentioning

confidence: 99%

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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: 50%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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 the classical MEN 2A -which is clinically characterized by the presence of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and primary HPT; in MEN 2B, where MTC is associated with pheochromocytoma and mucosal neuroma; and in familial MTC, genetic testing detects nearly 100% of RET proto-oncogene mutation carriers and is now considered the standard of care for all first degree relatives of patients with newly diagnosed MTC. Each variant of MEN 2 results from a different RET mutation, with a good genotype-phenotype correlation, allowing the design of good guidelines for timing of prophylactic thyroidectomy and extent of surgery based on risk levels (13).…”

Section: Discussionmentioning

confidence: 99%

“…However, patients with certain spo-one MEN 1 case plus at least 1 first degree relative with one of the three main MEN 1-related endocrine tumors (1). However, the expression of one or more of the less common tumors of MEN 1 can occur by chance, unlike syndromic variants that occur repeatedly in MEN 2, especially in sporadic cases (13). This was the situation of our patient, whose initial manifestation was Cushing's Disease at 20 years of age.…”

Section: Discussionmentioning

confidence: 99%

Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1

Boguszewski

Bianchet

Raskin³

et al. 2010

Arq Bras Endocrinol Metab

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We report the use of a genetic test for therapeutic decision making in a case of primary hyperparathyroidism associated with Cushing's disease (CD). A 20-year-old woman was evaluated for gradual weight gain, asthenia, muscle pain, and hypertension. Biochemical and radiologic tests confirmed CD and she underwent transsphenoidal surgery. Immunohistochemistry of the microadenoma was positive for adrenocorticotropic hormone (ACTH). On follow-up, hypercalcemia with high parathyroid hormone (PTH) levels was detected, associated with nephrolithiasis and low bone mineral density in the spine and hip. Parathyroid scintigraphy showed tracer uptake in the inferior region of the left thyroid lobe, and cervical ultrasound showed a heterogeneous nodule in the same area, suggestive of a parathyroid adenoma (PA). Genetic testing detected mutation in the MEN 1 gene and total parathyroidectomy with the implantation of a fragment of one gland in the forearm was performed. Pathology showed a PA and 3 normal parathyroid glands, without hyperplasia, despite the diagnosis of MEN 1. This case illustrates the role of genetic testing in defining the therapeutic approach for sporadic MEN 1.

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Constitutional Oncogenetics

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Genotype-phenotype relationship in multiple endocrine neoplasia type 2. Implications for clinical management

Abstract: ABSTRACT

Cited by 87 publications

References 23 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

Application of genetic testing to define the surgical approach in a sporadic case of multiple endocrine neoplasia type 1

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