Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Jul 13;2(8):933-943.
doi: 10.1210/js.2018-00178. eCollection 2018 Aug 1.

Update on Multiple Endocrine Neoplasia Type 2: Focus on Medullary Thyroid Carcinoma

Friedhelm Raue  1 , Karin Frank-Raue  1
Affiliations
Review

Update on Multiple Endocrine Neoplasia Type 2: Focus on Medullary Thyroid Carcinoma

Friedhelm Raue et al. J Endocr Soc. .

Abstract

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant hereditary cancer syndrome caused by missense gain-of-function mutations in the RET proto-oncogene on chromosome 10. Specific RET mutations can predispose toward a particular phenotype and clinical course, with strong genotype-phenotype correlations. MEN2 is highly penetrant in medullary thyroid carcinoma (MTC), and it can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. Two different clinical variants of MEN2 are known: MEN2A, which includes the familial subtype, and MEN2B. Treatment includes early thyroidectomy. Recommendations on the timing and extent of surgery are based on the RET mutation risk categories (moderate-, high-, or highest-risk) regarding the age of MTC onset. Early identification of patients with hereditary MTC has improved treatment outcomes. Previously, MTC was diagnosed based on clinical tumors; in contrast, with genetic screening, MTC can be diagnosed at preclinical disease states. This approach has resulted in a high cure rate and a much better prognosis for MTC. However, classification into one of the three RET mutation risk groups for predicting aggressiveness and prognosis has had limited impact. Increasing evidence has shown that patients with RET mutations in different risk classifications exhibit a broad spectrum of MTC aggressiveness during follow-up, with no relevant difference in survival. The specific germline activating mutation of the RET proto-oncogene appears to be the first determinant of the age of MTC onset, but, presumably, different regulatory events determine long-term tumor behavior.

Keywords: RET mutation; calcitonin; medullary thyroid carcinoma; multiple endocrine neoplasia type 2.

PubMed Disclaimer

References

    1. Raue F, Frank-Raue K. Update multiple endocrine neoplasia type 2. Fam Cancer. 2010;9(3):449–457. - PubMed
    1. Wells SA Jr, Pacini F, Robinson BG, Santoro M. Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: an update. J Clin Endocrinol Metab. 2013;98(8):3149–3164. - PMC - PubMed
    1. Wells SA Jr, Asa SL, Dralle H, Elisei R, Evans DB, Gagel RF, Lee N, Machens A, Moley JF, Pacini F, Raue F, Frank-Raue K, Robinson B, Rosenthal MS, Santoro M, Schlumberger M, Shah M, Waguespack SG; American Thyroid Association Guidelines Task Force on Medullary Thyroid Carcinoma . Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid. 2015;25(6):567–610. - PMC - PubMed
    1. Kloos RT, Eng C, Evans DB, Francis GL, Gagel RF, Gharib H, Moley JF, Pacini F, Ringel MD, Schlumberger M, Wells SA Jr; American Thyroid Association Guidelines Task Force . Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid. 2009;19(6):565–612. - PubMed
    1. Maia AL, Siqueira DR, Kulcsar MA, Tincani AJ, Mazeto GM, Maciel LM. Diagnosis, treatment, and follow-up of medullary thyroid carcinoma: recommendations by the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism. Arq Bras Endocrinol Metabol. 2014;58(7):667–700. - PubMed

LinkOut - more resources