Thyroidectomy for the Prevention of Medullary Thyroid Carcinoma
DESCRIPTION
Medullary thyroid cancer is surgically curable if detected before it has spread to regional lymph nodes. However, lymph node involvement at diagnosis may be found in up to 75% of individuals for whom a thyroid nodule is the first sign of disease. Medullary thyroid carcinoma often recurs and/or metastasizes despite complete thyroidectomy in those with positive lymph nodes. Thus, there is an emphasis on early detection and intervention in families affected by multiple endocrine neoplasia (MEN) types 2A and 2B or familial medullary thyroid cancer (FMTC). The development of invasive medullary thyroid cancer is usually preceded by C-cell hyperplasia, which can be detected by hypersecretion of calcitonin in response to a chemical challenge. Genetic assays for mutations have been used as an alternative to annual biochemical testing for C-cell hyperplasia in individuals with a known family history of MEN 2A, 2B, or FMTC. Annual biochemical screening can be stopped in those individuals who test negative for mutations. Individuals who test positive for mutations may undergo immediate prophylactic thyroidectomy or postpone thyroidectomy until biochemical tests suggest evolving medullary cancer.
Up to 9% of thyroid cancer (0.1% of all non-skin cancer) is classified histologically as medullary carcinoma. The familial cancer syndromes (MEN 2A, MEN 2B & FMTC) together are responsible for approximately one-fourth of the incidence of medullary carcinoma of the thyroid. Approximately 90% of the inherited medullary thyroid carcinoma occurs as MEN 2A, with MEN 2B and FMTC accounting for approximately 5% each. Over their lifetime, more than 95% of those who inherit a RET proto-oncogene point mutation will develop C-cell hyperplasia and/or medullary thyroid carcinoma if the gland is not removed before the disease is diagnosed by clinical symptoms. The average age of onset differs among the three inherited syndromes. Onset is less than 10 years of age for MEN 2B, near 20 years of age for MEN 2A, and between 40 and 50 years of age for FMTC. The inherited forms also differ in aggressiveness, with the tumors being most indolent in FMTC and most aggressive in MEN 2B.
POLICY
Prophylactic thyroidectomy for the prevention of medullary thyroid carcinoma is considered medically necessary if medical appropriateness criteria are met. (See Medical Appropriateness below.)
See also: Genetic Testing for Medullary Thyroid Carcinoma
MEDICAL APPROPRIATENESS
Prophylactic thyroidectomy for the prevention of medullary thyroid carcinoma is considered medically appropriate for an individual whose genetic testing is positive for RETS proto-oncogene point mutations.
ADDITIONAL INFORMATION
It is important that individuals with MEN 2A and MEN 2B have pheochromocytoma excluded before undergoing thyroidectomy. Pheochromocytoma is a chromaffin cell tumor of the sympathoadrenal system that produces catecholamines.
SOURCES
American Association of Clinical Endocrinologists. (2001, June). AACE/AAES medical/surgical guidelines for clinical practice: management of thyroid carcinoma. Retrieved January 31, 2003 from http://www.aace.com/clin/guidelines/thyroid_carcinoma.pdf.
BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2003). Genetic testing for germline mutations of the RET proto-oncogene in medullary carcinoma of the thyroid (2.04.05). Retrieved October 24, 2005 from BlueWeb.
Carreno, M., Girbes, J., Malluguiza, R., Serrano, S., Matias-Guiu, X., Gudela, J., et al. (2001). Usefulness of RET proto-oncogene in the diagnosis of hereditary-type medullary carcinoma of the thyroid. Correlation with surgical findings. Acta Otorrinolaringologica Espanola, 52 (1), 57-63. Abstract retrieved July 10, 2001 from PubMed database.
Hassett, S., Costigan, C., McDermott, M., & Fitzgerald, R. J. (2000). Prophylactic thyroidectomy in the treatment of thyroid medullary carcinoma. Age for surgery? European Journal of Pediatric Surgery, 10 (5), 334-336. Abstract retrieved July 10, 2001 from PubMed database.
Hoie, J., Heimdal, K., Nesland, J. M., & Bormer, O. (2000). Prophylactic thyroidectomy in carriers of RET oncogene mutation carriers. Tidsskrift for den Norske Laegeforening, 120 (27), 3249-3252. Abstract retrieved July 11, 2001 from PubMed database.
Kebebew, E., Tresler, P. A., Siperstein, A. E., Duh, Q. Y., & Clark, O. H. (1999). Normal thyroid pathology in patients undergoing thyroidectomy for finding a RETgene germline mutation: a report of three cases and review of the literature. Thyroid, 9 (2), 127-131. Abstract retrieved July 11, 2001 from PubMed database.
Niccoli-Sire, P., Murat, A., Baudin, E., Henry, J. F., Proye, C., Bigorgne, J. C., et al. (1999). Early or prophylactic thyroidectomy in MEN 2/FMTC gene carriers: results in 71 thyroidectomized patients. The French Calcitonin Tumours Study Group (GETC). European Journal of Endocrinology, 141(5), 468-474. Abstract retrieved July 11, 2001 from PubMed database.
Skinner, M. A., Moley, J. A., Dilley, W. G., Owzar, K., DeBenedetti, M. K., & Wells, S. A. (2005). Prophylactic thyroidectomy in multiple endocrine neoplasia type 2a. The New England Journal of Medicine, 353 (11), 1105-1113.
The Technology Evaluation Center. (1997, August). Genetic testing for germline mutations of the RET proto-oncogene in medullary carcinoma of the thyroid (Vol. 12, No. 12). Chicago: BlueCross BlueShield Association.
Torre, M., Martucciello, G., Ceccherini, I., Lerone, M., Aicardi, M., Gambini, C., et al. (2002). Diagnostic and therapeutic approach to multiple endocrine neoplasia type 2B in pediatric patients. Pediatric Surgery International, 18 (5-6), 378-383.
Ukkat, J., Lorenz, K., Hinze, R., Thomusch, O., & Dralle, H. (2001). Importance of early screening and prophylactic thyroidectomy in asymptomatic nonindex ret germline carriers. World Journal of Surgery, 25 (6), 713-717. Abstract retrieved July 10, 2001 from PubMed database.
van Heurn, L. W., Schaap, C., Sie, G., Haagen, A. A., Gerver, W. J., Freling, G., et al. (1999). Predictive DNA testing for multiple endocrine neoplasia 2: a therapeutic challenge of prophylactic thyroidectomy in very young children. Journal of Pediatric Surgery, 34 (4), 568-571. Abstract retrieved September 16, 1999 from PubMed database.
Wells, S. A. Jr., Chi, D. D., Toshima, K., Dehner, L. P., Coffin, V. M., Dowton, S. B., et al. (1994). Predictive DNA testing and prophylactic thyroidectomy in patients at risk for multiple endocrine neoplasia type 2A. Annals of Surgery, 220 (3), 237-247. Abstract retrieved April 29, 1999 from PubMed database.
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EFFECTIVE DATE |
12/8/2005 |
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