ATA Guidelines Tools

Key Points Î Medullary Thyroid Carcinoma (MTC) represents a unique thyroid cancer that occurs either sporadically or in a hereditary form as a component of the type 2 multiple endocrine neoplasia (MEN) syndromes, MEN2A, MEN2B, and the related syndrome, familial MTC (FMTC). Î Medullary thyroid carcinoma accounts for 1-2% of thyroid cancers in the United States, a much lower range than frequently cited (3-5%) primarily due to the marked increase in the relative incidence of papillary thyroid carcinoma (PTC) over the last three decades. Î Virtually all patients with MEN2A, MEN2B, and FMTC have RET germline mutations, and approximately 50% of sporadic MTCs have somatic RET mutations. • The RET protooncogene (REarranged during Transfection), located on chromosome 10q11.2, encodes a single-pass transmembrane receptor of the tyrosine kinase family. Of sporadic MTCs lacking somatic RET mutations, 18- 80% have somatic mutations of HRAS, KRAS, or rarely NRAS. Î RET is a remarkable oncogene that is central not only to the development of sporadic and hereditary MTC but also to other malignant and non-malignant diseases. Î Over 100 mutations, duplications, insertions, or deletions involving RET have been identified in patients with MTC. The aggressiveness of MTC varies with the RET mutation. Therefore, treatment should be guided by genetic testing. (Table 2 summarizes the relative risk of developing an aggressive MTC and the other endocrine tumors and diseases associated with MEN2A and MEN2B.) Table 1. Recommendation Grading Grade Rating Rating Definition A Strongly recommends Good evidence that the service or intervention can improve important health outcomes B Recommends Fair evidence that the service or intervention can improve important health outcomes C Recommends Expert opinion D Recommends against Expert opinion E Recommends against Fair evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits F Strongly recommends against Good evidence that the service or intervention does not improve important health outcomes or that harms outweigh benefits I Recommends neither for nor against e evidence is insufficient to recommend for or against providing the service or intervention because evidence is lacking that the service or intervention improves important health outcomes, the evidence is of poor quality, or the evidence is conflicting. Adapted from the U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality. Capital letters in parentheses are used subsequently to express the strength of the Task Force's Recommendation based on available evidence.

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