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  • Review Article
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Primary hypothyroidism and quality of life

Nature Reviews Endocrinology volume 18, pages 230–242 (2022)Cite this article

Subjects

Abstract

In the 1970s, treatment with thyroid extract was superseded by levothyroxine, a synthetic l form of tetraiodothyronine. Since then, no major innovation has emerged for the treatment of hypothyroidism. The biochemical definition of subclinical hypothyroidism is a matter of debate. Indiscriminate screening for hypothyroidism has led to overdiagnosis and treatment initiation at lower serum levels of thyroid-stimulating hormone (TSH) than previously. Adverse health effects have been documented in individuals with hypothyroidism or hyperthyroidism, and these adverse effects can affect health-related quality of life (QOL). Levothyroxine substitution improves, but does not always normalize, QOL, especially for individuals with mild hypothyroidism. However, neither studies combining levothyroxine and liothyronine (the synthetic form of tri-iodothyronine) nor the use of desiccated thyroid extract have shown robust improvements in patient satisfaction. Future studies should focus not only on a better understanding of an individual’s TSH set point (the innate narrow physiological range of serum concentration of TSH in an individual, before the onset of hypothyroidism) and alternative thyroid hormone combinations and formulations, but also on autoimmunity and comorbidities unrelated to hypothyroidism as drivers of patient dissatisfaction. Attention to the long-term health consequences of hypothyroidism, beyond QOL, and the risks of overtreatment is imperative.

Key points

  • Epidemiological data suggest that the prevalence of (typically mild) hypothyroidism is increasing, partly owing to increased screening, which has led to a lower threshold for initiating treatment with levothyroxine.

  • Approximately 10–15% of individuals with hypothyroidism treated with levothyroxine experience persistent symptoms and dissatisfaction with therapy (that might or might not be due to their hypothyroidism), which can lead to overtreatment.

  • Health-related quality of life (QOL) is a complementary measure to morbidity and mortality; it should be measured with a validated thyroid-specific instrument for patient-related outcomes.

  • Poor QOL has been attributed to failure to achieve adequate T3 levels in tissues, polymorphisms in deiodinase and hormone transporter genes and/or symptoms unrelated to hypothyroidism such as autoimmune disease.

  • There is little evidence of durable QOL improvements with levothyroxine and liothyronine combination therapy, or from therapy with desiccated thyroid hormone, from a multitude of randomized controlled trials and meta-analyses.

  • Future research should investigate non-thyroidal causes of impaired QOL in patients with hypothyroidism as, at present, overtreatment for hypothyroidism constitutes a greater threat to health than undertreatment.

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Fig. 1: Roles of the DIO1 and DIO2 pathways in the TSH feedback mechanism during treatment with levothyroxine.
Fig. 2: Proportion of dissatisfaction expressed by patients with self-reported hypothyroidism by type of treatment for hypothyroidism.
Fig. 3: Changes in components of QOL before and after treatment of hypothyroidism.

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Acknowledgements

J.J. has received support from NIDCR grant R01DE025822 and NCATS grant UL1TR001409. A.C.B. has received support from NIH grants DK58538 and DK65055.

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Authors and Affiliations

  1. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Laszlo Hegedüs

  2. Section of Adult and Paediatric Endocrinology, Diabetes & Metabolism, Department of Medicine, University of Chicago, Chicago, IL, USA

    Antonio C. Bianco

  3. Division of Endocrinology, Georgetown University, Washington, DC, USA

    Jacqueline Jonklaas

  4. Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK

    Simon H. Pearce

  5. Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK

    Simon H. Pearce & Petros Perros

  6. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    Anthony P. Weetman

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L.H., A.C.B., J.J., S.H.P., A.P.W. and P.P. researched data for the article, wrote the article, contributed substantially to the discussion of content and reviewed and edited the manuscript before submission.

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Correspondence to Laszlo Hegedüs.

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Competing interests

S.H.P. has received speaker fees from Quidel, Sanofi and Berlin Chemie, and consulting fees from Apitope. P.P. has received consulting fees from IBSA Institut Biochimique and speaker fees from Berlin Chemie. L.H. has received consulting fees from IBSA Institut Biochimique and speaker fees from Berlin Chemie. A.C.B. is a consultant for AbbVie, Allergan, Synthonics, Sention, and Thyron. J.J. and A.P.W. declare no competing interests.

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Glossary

Free T4

T4 that is not bound to protein in the circulation and is therefore available to act on tissues

Acrophase

The time at which a peak in a circadian rhythm occurs

Thyrotrophs

Cells in the anterior pituitary gland that secrete TSH

Tanycytes

Specialized ependymal cells lining the walls of the third ventricle

Responsive

The responsiveness of an instrument determines its ability to detect relevant clinical changes over time

Acceptable

How acceptable an instrument is determines its ease of use by participants

Test–retest reliability

Stability of the scores obtained from the same person on two or more separate occasions

Minimal important change

The smallest change in an outcome that is perceived by an individual patient as important

Thyrotoxic

A metabolic state characterized by elevated serum levels of tri-iodothyronine

Content validity

Extent to which the items tested are representative of the entire domain the test seeks to measure

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Hegedüs, L., Bianco, A.C., Jonklaas, J. et al. Primary hypothyroidism and quality of life. Nat Rev Endocrinol 18, 230–242 (2022). https://doi.org/10.1038/s41574-021-00625-8

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