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. 2012 Jul;1(2):55-71.
doi: 10.1159/000339444. Epub 2012 Jun 13.

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

Wilmar M Wiersinga  1 , Leonidas Duntas  2 , Valentin Fadeyev  3 , Birte Nygaard  4 , Mark P J Vanderpump  5
Affiliations

2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism

Wilmar M Wiersinga et al. Eur Thyroid J. 2012 Jul.

Abstract

Background: Data suggest symptoms of hypothyroidism persist in 5-10% of levothyroxine (L-T4)-treated hypothyroid patients with normal serum thyrotrophin (TSH). The use of L-T4 + liothyronine (L-T3) combination therapy in such patients is controversial. The ETA nominated a task force to review the topic and formulate guidelines in this area.

Methods: Task force members developed a list of relevant topics. Recommendations on each topic are based on a systematic literature search, discussions within the task force, and comments from the European Thyroid Association (ETA) membership at large.

Results: SUGGESTED EXPLANATIONS FOR PERSISTING SYMPTOMS INCLUDE: awareness of a chronic disease, presence of associated autoimmune diseases, thyroid autoimmunity per se, and inadequacy of L-T4 treatment to restore physiological thyroxine (T4) and triiodothyronine (T3) concentrations in serum and tissues. There is insufficient evidence that L-T4 + L-T3 combination therapy is better than L-T4 monotherapy, and it is recommended that L-T4 monotherapy remains the standard treatment of hypothyroidism. L-T4 + L-T3 combination therapy might be considered as an experimental approach in compliant L-T4-treated hypothyroid patients who have persistent complaints despite serum TSH values within the reference range, provided they have previously received support to deal with the chronic nature of their disease, and associated autoimmune diseases have been excluded. Treatment should only be instituted by accredited internists/endocrinologists, and discontinued if no improvement is experienced after 3 months. It is suggested to start combination therapy in an L-T4/L-T3 dose ratio between 13:1 and 20:1 by weight (L-T4 once daily, and the daily L-T3 dose in two doses). Currently available combined preparations all have an L-T4/L-T3 dose ratio of less than 13:1, and are not recommended. Close monitoring is indicated, aiming not only to normalize serum TSH and free T4 but also normal serum free T4/free T3 ratios. Suggestions are made for further research.

Conclusion: L-T4 + L-T3 combination therapy should be considered solely as an experimental treatment modality. The present guidelines are offered to enhance its safety and to counter its indiscriminate use.

Keywords: Combination therapy; Guidelines; Hypothyroidism; Thyroxine; Treatment; Triiodothyronine.

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References

    1. Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R. Thyroidal and peripheral production of 3,5,3′-triiodothyronine in humans by multicompartmental analysis. Am J Physiol. 1990;258:E715–E726. - PubMed
    1. Singer PA, Cooper DS, Levy EG, Ladenson PW, Braverman LE, Daniels G, Greenspan FS, McDougall IR, Nikolai TF. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. JAMA. 1995;273:808–812. - PubMed
    1. Baskin HJ, Cobin RH, Duick DS, Gharib H, Guttler RB, Kaplan MM, Segal RL. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract. 2002;6:457–469. - PubMed
    1. www.hypomaarniethappy.nl
    1. Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J. Effect of combination therapy with thyroxine (T4) and 3,5,3′-triiodothyronine (T3) versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomized cross-over study. Eur J Endocrinol. 2009;161:895–902. - PubMed