Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 9;43(2):366-404.
doi: 10.1210/endrev/bnab031.

Optimal Thyroid Hormone Replacement

Jacqueline Jonklaas  1
Affiliations

Optimal Thyroid Hormone Replacement

Jacqueline Jonklaas. Endocr Rev. .

Abstract

Hypothyroidism is a common endocrinopathy, and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed on, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, comorbidities, thyrotropin goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. Because levothyroxine is a lifelong medication, it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient's life (coexistent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower-quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy be continued only as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy. A sustained-release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.

Keywords: euthyroidism; hypothyroidism; levothyroxine; liothyronine; patient-reported outcomes; quality-of-life.

PubMed Disclaimer

Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
Examples of effects of hypothyroidism on organs and tissues in the adult, including signs, symptoms, and “biomarkers.”
Figure 2.
Figure 2.
Thyrotropin (TSH)-based adjustments in levothyroxine dose.
Figure 3.
Figure 3.
Levothyroxine doses available for dosage titration.
Figure 4.
Figure 4.
Effect of timing of levothyroxine ingestion on serum thyrotropin (TSH).
Figure 5.
Figure 5.
Potential causes of symptoms in patients with a normal thyrotropin (TSH).
See this image and copyright information in PMC

References

    1. Jonklaas J, Bianco AC, Bauer AJ, et al. ; American Thyroid Association Task Force on Thyroid Hormone Replacement . Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751. - PMC - PubMed
    1. Slater S. The discovery of thyroid replacement therapy. Part 1: in the beginning. J R Soc Med. 2011;104(1):15-18. - PMC - PubMed
    1. Slater S. The discovery of thyroid replacement therapy. Part 3: a complete transformation. J R Soc Med. 2011;104(3):100-106. - PMC - PubMed
    1. Beadles C. The treatment of myxoedema and cretinism, being a review of the treatment of these diseases with the thyroid gland, with a table of 100 published cases. J Mental Science. 1893;39:509-536.
    1. Bramwell B. The thyroid treatment of myxoedema and sporadic cretinism, with notes of twenty-three cases of myxoedema and five cases of sporadic cretinism, treated by thyroid extract. Edinburgh Hosp Rep. 1895;3:116-249.

Publication types