Hereditary medullary thyroid carcinoma: the management dilemma

Abstract

Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25-30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype-phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.

A new genome scan for primary nonsyndromic vesicoureteric reflux emphasizes high genetic heterogeneity and shows linkage and association with various genes already implicated in urinary tract development

“…), and isolated medullary carcinoma of thyroid (Zhou et al. ); one nonsynonymous variant was thought to cause VUR (Yang et al. ), but this was shown not to be so (Darlow et al.…”

“…Indeed, there are genes known to be involved in urinary tract development in which no mutations have been found that cause isolated VUR. For instance, mutations in RET can cause Hirschsprung's Disease (Wallace and Anderson 2011), Multiple Endocrine Neoplasia Type 2 (Pasquali et al 2012), and isolated medullary carcinoma of thyroid (Zhou et al 2012); one nonsynonymous variant was thought to cause VUR (Yang et al 2008), but this was shown not to be so (Darlow et al 2009).…”

Genes of detoxification are important modulators of hereditary medullary thyroid carcinoma risk

“…7 In addition, codon-specific phenotypes for RET mutation detection provide the basis for individualized risk evaluation and prophylactic thyroidectomy in carriers. 8,9 However, the clinical characteristics and the progression of MTC patients present considerable variability. MTC typically occurs in early childhood in MEN 2B, predominantly in early adulthood in MEN 2A and in middle age for FMTC.…”