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Hereditary and Sporadic Medullary Thyroid Carcinoma

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Neuroendocrine Tumors

Part of the book series: Current Clinical Oncology ((CCO))

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Abstract

Medullary thyroid carcinoma (MTC) is an uncommon neuroendocrine tumor that arises from the parafollicular cells of the thyroid gland. These cells ­produce calcitonin, a peptide that is a useful marker of disease. MTC accounts for approximately 5% of all thyroid carcinomas. Most of the cases are sporadic; 25–30% is hereditary and associated with the multiple endocrine neoplasia type 2 syndrome (MEN2). In 1961, 2 years after the initial description of MTC by Hazard and ­colleagues, Sipple described the association of MTC with pheochromocytoma, a syndrome that was later denominated multiple endocrine neoplasia type 2 (MEN2). For the past 5 decades, an extensive amount of knowledge has been acquired. Before the discovery of the genetic abnormality associated with the syndrome, the diagnosis and management of patients with hereditary MTC and their family members were based on basal and stimulated levels of calcitonin. In this context, families with MEN2 were characterized, variants of MEN2 were identified, and carriers identified by biochemical screening were treated with thyroidectomy. With the ­discovery of the gene associated with MEN2 (RET gene) in 1993, management was further refined and genetic analysis became the most sensitive and specific modality to distinguish normal individuals from carriers of MEN2, and the risk of performing a prophylactic thyroidectomy in a normal individual was not a concern anymore. In these past 15 years, new knowledge continues to emerge. We can now correlate fine differences in phenotype with different types of RET mutations and have questioned the significance of different genetic backgrounds, specifically RET polymorphisms, in time of onset and aggressiveness of disease. Furthermore, the discovery of how the RET receptor functions and which signaling pathways are activated has permitted the development of small molecules that target these pathways, inhibiting cell proliferation and tumor growth.

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Authors and Affiliations

  1. Department of Endocrinology, Fleury Group, São Paulo, Brazil

    Ana O. Hoff

  2. Endocrine Neoplasia Unit, Instituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil

    Ana O. Hoff

  3. Department of Endocrinology, Federal University of São Paulo, São Paulo, Brazil

    Cleber Camacho MD & Rui M. B. Maciel

  4. Section of Endocrinology, Fleury Group, São Paulo, Brazil

    Rui M. B. Maciel

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  1. Ana O. Hoff
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  2. Cleber Camacho MD
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  3. Rui M. B. Maciel
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Correspondence to Ana O. Hoff .

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  1. MD Anderson Cancer Center, Department of Gastrointestinal, University of Texas, Holcombe Blvd. 1400, Houston, 77030-4009, Texas, USA

    James C. Yao

  2. São Paulo, Faculdade de Medicina da, Universidade de São Paulo,, Instituto do Cancer do Estado de, Ave Dr Arnaldo 251, São Paulo, 01246-000, São Paulo, Brazil

    Paulo M. Hoff

  3. Cancer do Estado de São Paulo, Faculdade, de Medicina da Universidade de São Paulo, Endocrine Neoplasia Unit, Instituto do, Av Dr Arnaldo 251, São Paulo, 01246-000, São Paulo, Brazil

    Ana O. Hoff

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Hoff, A.O., Camacho, C., Maciel, R.M.B. (2011). Hereditary and Sporadic Medullary Thyroid Carcinoma. In: Yao, J., Hoff, P., Hoff, A. (eds) Neuroendocrine Tumors. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-60327-997-0_11

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