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Treatment for hypothyroidism

Hypothyroidism is due to an underactive thyroid gland. This means that the thyroid gland can’t make enough thyroid hormone to keep the body running normally. The major form of thyroid hormone in the blood is Levothyroxine (T4), and Triiodothyronine (T3). The goal of therapy is to reverse all the clinical manifestations of hypothyroidism. This can be accomplished by oral administration of synthetic thyroxine (T4, levothyroxine). It has been suggested that the addition of T3 may be of benefit for some patients.

Desiccated thyroid or thyroid extract refers to dried porcine thyroid glands in therapeutic use. The earliest oral treatment for hypothyroidism consisted of thyroid extract. In the early 1960s, desiccated thyroid hormones began to be replaced by levothyroxine (T4), or by combinations of T4 and T3.

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SBU Enquiry Service

Consists of structured literature searches to highlight studies that can address questions received by the SBU Enquiry Service from Swedish healthcare or social service providers. We assess the risk of bias in systematic reviews and when needed also quality and transferability of results in health economic studies. Relevant references are compiled by an SBU staff member, in consultation with an external expert when needed.

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Questions

  • Is combination therapy (tyroxin, T4, and triiodothyronin, T3) more effective than monotherapy (tyroxin, T4) for patients with hypothyroidism?
  • Is thyroid extract more effective than levothyroxine (T4) for patients with hypothyroidism?

Identified studies

  1. Kraut E, Farahani P. A Systematic Review of Clinical Practice Guidelines' Recommendations on Levothyroxine Therapy Alone versus Combination Therapy (LT4 plus LT3) for Hypothyroidism. Clin Invest Med 2015;38:E305-13.
  2. Nygaard B. Hypothyroidism (primary). BMJ Clin Evid 2014;2014.
  3. Joffe RT, Brimacombe M, Levitt AJ, Stagnaro-Green A. Treatment of clinical hypothyroidism with thyroxine and triiodothyronine: A literature review and metaanalysis. Psychosomatics 2007;48:379-384.
  4. Grozinsky-Glasberg S, Fraser A, Nahshoni E, Weizman A, Leibovici L. Thyroxine-triiodothyronine combination therapy versus thyroxine monotherapy for clinical hypothyroidism: Meta-analysis of randomized controlled trials. Journal of Clinical Endocrinology and Metabolism 2006;91:2592-2599.
  5. Ma C, Xie J, Huang X, Wang G, Wang Y, Wang X, et al. Thyroxine alone or thyroxine plus triiodothyronine replacement therapy for hypothyroidism. Nucl Med Commun 2009;30:586-93.
  6. Biondi B, Wartofsky L. Combination treatment with T4 and T3: toward personalized replacement therapy in hypothyroidism? J Clin Endocrinol Metab 2012;97:2256-71.
  7. Escobar-Morreale HF, Botella-Carretero JI, Escobar del Rey F, Morreale de Escobar G. REVIEW: Treatment of hypothyroidism with combinations of levothyroxine plus liothyronine. J Clin Endocrinol Metab 2005;90:4946-54.
  8. Kaminski J, Miasaki FY, Paz-Filho G, Graf H, Carvalho GA. Treatment of hypothyroidism with levothyroxine plus liothyronine: a randomized, double-blind, crossover study. Arch Endocrinol Metab 2016;60:562-572.
  9. Carle A, Laurberg P, Steffensen R, Faber J, Nygaard B. Combination of DIO2 and MCT10 gene polymorphisms predicts the preference for T4+T3 therapy in hypothyroidism-a blinded randomized clinical study. European Thyroid Journal 2016;5:65-66.
  10. Nygaard B, Jensen EW, Kvetny J, Jarlov A, Faber J. Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. European Journal of Endocrinology 2009;161:895-902.
  11. Schmidt U, Nygaard B, Jensen E, Kvetny J, Jarlov A, Faber J. Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study. Endocrine connections 2013;2:55-60.
  12. Fadeyev VV, Morgunova TB, Melnichenko GA, Dedov II. Combined therapy with L-Thyroxine and L-Tiiodothyronine compared to L-Thyroxine alone in the treatment of primary hypothyroidism. Hormones 2010;9:245-252.
  13. Valizadeh M, Seyyed-Majidi MR, Hajibeigloo H, Momtazi S, Musavinasab N, Hayatbakhsh MR. Efficacy of combined levothyroxine and liothyronine as compared with levothyroxine monotherapy in primary hypothyroidism: A randomized controlled trial. Endocrine Research 2009;34:80-89.
  14. Hoang T, Olsen C, Mai V, Clyde P, Shakir M. Desiccated thyroid extract compared with levothyroxine in the treatment of hypothyroidism: a randomized, double-blind, crossover study. Journal of clinical endocrinology and metabolism 2013;98:1982-1990.
  15. Pepper GM, Casanova-Romero PY (2014) Conversion to Armour Thyroid from Levothyroxine Improved Patient Satisfaction in the Treatment of Hypothyroidism. J Endocrinol Diabetes Obes 2(3): 1055.
  16. Felt V, Nedvidkova J. A comparison of the treatment with L-thyroxine and with preparation of dried thyroid gland in patients with hypothyreosis. Vnitrni Lekarstvi 1982;28:1067-1073.
  17. Zgliczynska-Widlak J. [Treatment of hypothyroidism with L-thyroxin]. Endokrynol Pol 1992;43:298-307.
  18. Caron P, Camare R, Bennet A, Perret B, Hoff M, Louvet JP. A comparative study of lipid parameters in patients with hypothyroidism well controlled by thyroid extract or levothyroxine. Semaine des Hopitaux 1991;67:449-453.
  19. Górowski T, Puciłowska J, Wernic K. [Comparative effects of desiccated thyroid gland and sodium salt of L-thyroxine in the treatment of hypothyroidism]. In: Polski tygodnik lekarski (Warsaw, Poland : 1960); 1989. p 768-70.
  20. Caron P, Couture E, Hoff M, Bennet A, Louvet JP. Treatment of primary hypothyroidism in adults: Desiccated thyroid versus L-thyroxine. Semaine des Hopitaux 1988;64:1777-1780.
  21. Bindels AJ, Meinders AE. The serum concentrations of T3, T4 and TSH in evaluating replacement therapy in primary hypothyroidism. Neth J Med 1988;32:59-71.
  22. Baillet J, Paillard J, Behar A. Effectiveness of various hormonal preparations in adults with hypothyroidism. Nouvelle Presse Medicale 1981;10:235-237.
  23. Krenning EP, Docter R, Visser TJ, Hennemann G. Replacement therapy with L-thyroxine. Netherlands Journal of Medicine 1981;24:1-5.
  24. Penny R, Frasier SD. Elevated serum concentrations of triiodothyronine in hypothyroid patients. Values for patients receiving USP thyroid. American Journal of Diseases of Children 1980;134:16-18.
  25. Jackson Cobb IMDWE. Why does anyone still use desiccated thyroid USP? American Journal of Medicine 1978;64:284-288.

Literature search

Literature search.pdf

Project group

Christel Hellberg, Miriam Entesarian Matsson, Jessica Dagerhamn, Anders Norlund, Anna Roehring Florczyk and Jan Liliemark at SBU.

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