Abstract
Levothyroxine (L-T4) is arguably the most prescribed medication in the United States, with its primary therapeutic indication for hypothyroidism from chronic thyroiditis or Hashimoto’s disease. Such patients are candidates for so-called replacement dosage, with the administered dosage of L-T4 titrated to a target thyrotropin (TSH) level within the normal range of 0.4–2.0 mU/L. Patients with thyroid cancer who have had near-total to total thyroidectomy are usually candidates for suppressive levothyroxine dosage, which is “so-called” because the aim of therapy is to give a slightly supraphysiologic dosage of thyroxine to suppress TSH. The rationale for suppressive therapy is based on studies indicating that TSH stimulation enhances tumor growth, TSH serving as a growth factor or mitogen for thyroid malignancies with observations of more rapid tumor growth seen clinically after thyroxine withdrawal. The growth-promoting property of TSH is presumed to be from the presence of TSH receptors on thyroid cancer cells (1); however, non-TSH receptor-mediated growth is certainly a property of undifferentiated thyroid cancers.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Carayon P, Thomnas-Morvan C, Castan E, Tubiana M. Human thyroid cancer: Membrane thyrotropin binding and adenylate cyclase activity. J Clin Endocrinol Metab 1980; 51:915–920.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer. Am J Med 1994; 97:418–428.
Pujol P, Daures J-P, Nsakala N, et al. Degree of thyrotropin suppression as a prognostic determinant in differentiated thyroid cancer. J Clin Endocrinol Metab 1996; 81:4318–4322.
National Comprehensive Cancer Network (NCCN) Thyroid Carcinoma: Clinical Practice Guidelines 2005, J Natl Comprehensive Cancer Network 2005; 3:404–457.
British Thyroid Association. Guidelines for the management of differentiated thyroid cancer in adults. Available at: www.british-thyroidassociation. org/guidelines.htm, 2002.
Sawin CT, Geller A, Wolf PA, et al. Low serum thyrotropin concentrations as a risk factor for atrial fibrillation in older persons. N Engl J Med 1994; 331:1249–1252.
Parle JV, Maisonneuve P, Sheppard MC, et al. Prediction of all-cause and cardiovascular mortality in elderly people from one low serum thyrotropin result: a 10-year cohort study. Lancet 2001; 358:861–865.
Fazio S, Palmieri EA, Lombardi G, Biondi B. Effects of thyroid hormone on the cardiovascular system. Recent Prog Horm Res 2004; 59:31–50.
Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002; 137:904–914.
Stathatos N, Wartofsky L. Effects of thyroid hormone on bone. Clin Rev Bone Mineral Metab 2004; 2:135–150.
Mikosch P, Obermayer-Pietsch B, Jost R, et al. Bone metabolism in patients with differentiated thyroid carcinoma receiving suppressive levothyroxine treatment. Thyroid 2003; 13:347–356.
Katz M, Rosen DL, Wartofsky L. Issues in bioequivalence and therapeutic equivalence of levothyroxine products. US Pharm 2003; 9(Suppl):2–14.
Wartofsky L. Levothyroxine: Therapeutic use and regulatory issues related to bioequivalence. Expert Opin Pharmacother 2002; 3:727–732.
Thyroid Foundation of America. Advice to patients from the Thyroid Foundation of America. Thyroid 2004; 14:487.
American Thyroid Association, Endocrine Society, American Association of Clinical Endocrinologists. Joint Statement on the U.S. Food and Drug Administration’s decision regarding bioequivalence of levothyroxine sodium. Thyroid 2 2004; 14:486.
Cooper DS, Specker B, Ho M, et al. Thyrotropin suppression and disease progression in patients with differentiated thyroid cancer: Results from the National Thyroid Cancer Treatment Cooperative Registry. Thyroid 1998; 9:737–744.
AACE/AAES Medical/Surgical guidelines for clinical practice: management of thyroid carcinoma. Endocr Pract 2001; 7:1–19.
Singer PA, Cooper DA, Daniels GH, et al. Treatment guidelines for patients with thyroid nodules and well differentiated thyroid cancer. Arch Int Med 1996; 156:2165–2172.
Cooper DS. Combined T4 and T3 therapy—back to the drawing board. JAMA 2003; 290:3002–3004.
Kaplan MM, Sarne DH, Schneider AB. Editorial: In search of the impossible dream? Thyroid hormone replacement therapy that treats all symptoms in all hypothyroid patients. J Clin Endocrinol Metab 2003; 88:4540–4542.
Carr D, McLeod DT, Parry G, et al. Fine adjustment of thyroxine replacement dosge: comparison of thyrotrophin releasing hormone test using a sensitive thyrotrophin assay with measurement of free thyroid hormones and clinical assessment. Clin Endocrinol 1988; 28:325–333.
Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange AJ, Jr. Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 1999; 340:424–429.
Escobar-Morreale HF, Escobar del Rey FE, Obregon MJ, Morreale de Escobar G. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology 1996; 137:2490–2502.
Escobar-Morreale HF, Botella-Carretero JI, Gomez-Bueno M, et al. Thyroid hormone replacement therapy in primary hypothyroidism: A randomized trial comparing L-thyroxine plus liothyronine with L-thyroxine alone. Ann Intern Med 2005; 142:412–424.
Toft AD. Thyroid hormone replacement-one hormone or two? N Engl J Med 1999; 340:469–470.
Clyde PW, Harari AE, Getka EJ, Shakir KMM. Combined levothyroxine plus liothyronine compared with levothyroxine alone in primary hypothyroidism. JAMA 2003; 290:2952–2958.
Levitt A, Silverberg J. T4 plus T3 treatment for hypothyroidism: a double-blind comparison with usual T4. Los Angeles, CA: Program 74th Annual Meeting, American Thyroid Association, 2002, 112.
Sawka AM, Gerstein HC, Marriott MJ, et al. Does a combination regimen of thyroxine (T4) and 3,5,3′-triiodothyronine improve depressive symptoms better than T4 alone in patients with hypothyroidism? Results of a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 2003; 88:4551–4555.
Walsh JP, Shiels L, Lim EM, et al. Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, or cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 2003; 88:4543–4550.
Cassio A, Cacciari E, Cicognani A, et al. Treatment for congenital hypothyroidism: thyroxine alone or thyroxine plus triiodothyronine? Pediatrics 2003; 111:1055–1060.
Siegmund W, Spieker K, Weike AI, et al. Replacement therapy with levothyroxine plus triiodothyronine (bioavailable molar ratio 14:1) is not superior to thyroxine alone to improve well-being and cognitive performance in hypothyroidism. Clin Endocrinol 2004; 60:750–757.
McGriff NJ, Csako G, Gourgiotis L, et al. Effects of thyroid hormone suppression therapy on adverse clinical outcomes in thyroid cancer. Ann Med 2002; 34:554–564.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Humana Press Inc., Totowa, NJ
About this chapter
Cite this chapter
Wartofsky, L. (2006). Levothyroxine Therapy and Thyrotropin Suppression. In: Wartofsky, L., Van Nostrand, D. (eds) Thyroid Cancer. Humana Press. https://doi.org/10.1007/978-1-59259-995-0_29
Download citation
DOI: https://doi.org/10.1007/978-1-59259-995-0_29
Publisher Name: Humana Press
Print ISBN: 978-1-58829-462-3
Online ISBN: 978-1-59259-995-0
eBook Packages: MedicineMedicine (R0)