Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline
Open accessAbstract
Clinical question: What are the benefits and harms of thyroid hormones for adults with subclinical hypothyroidism (SCH)? This guideline was triggered by a recent systematic review of randomised controlled trials, which could alter practice. Current practice: Current guidelines tend to recommend thyroid hormones for adults with thyroid stimulating hormone (TSH) levels >10 mIU/L and for people with lower TSH values who are young, symptomatic, or have specific indications for prescribing. Recommendation: The guideline panel issues a strong recommendation against thyroid hormones in adults with SCH (elevated TSH levels and normal free T4 (thyroxine) levels). It does not apply to women who are trying to become pregnant or patients with TSH >20 mIU/L. It may not apply to patients with severe symptoms or young adults (such as those ≤30 years old). How this guideline was created: A guideline panel including patients, clinicians, and methodologists produced this recommendation in adherence with standards for trustworthy guidelines using the GRADE approach. The evidence: The systematic review included 21 trials with 2192 participants. For adults with SCH, thyroid hormones consistently demonstrate no clinically relevant benefits for quality of life or thyroid related symptoms, including depressive symptoms, fatigue, and body mass index (moderate to high quality evidence). Thyroid hormones may have little or no effect on cardiovascular events or mortality (low quality evidence), but harms were measured in only one trial with few events at two years’ follow-up. Understanding the recommendation: The panel concluded that almost all adults with SCH would not benefit from treatment with thyroid hormones. Other factors in the strong recommendation include the burden of lifelong management and uncertainty on potential harms. Instead, clinicians should monitor the progression or resolution of the thyroid dysfunction in these adults. Recommendations are made actionable for clinicians and their patients through visual overviews. These provide the relative and absolute benefits and harms of thyroid hormones in multilayered evidence summaries and decision aids available in MAGIC ( https://app.magicapp.org/ ) to support shared decisions and adaptation of this guideline.
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A 2019 guideline panel issued a strong recommendation against thyroid hormones in adults with subclinical hypothyroidism (with exceptions).
“A guideline panel including patients, clinicians, and methodologists issued in 2019 a strong recommendation against thyroid hormones in adults with subclinical hypothyroidism (which may not apply to pregnant women, patients with TSH >20 mU/L, patients with severe symptoms, or young adults ≤30 years of age) [55].”
From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [55]
Current clinical guidelines propose that thyroid hormone replacement therapy should not be routinely offered for adults with subclinical hypothyroidism.
“which is supported by current clinical guidelines proposing that thyroid hormone replacement therapy should not be routinely offered for adults with subclinical hypothyroidism.12,13,14”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [12]
It remains unclear whether thyroid hormone replacement therapy is effective in mitigating several long-term adverse outcomes, such as CVD and death, in the general population with subclinical hypothyroidism.
“However, it remains unclear whether thyroid hormone replacement therapy is effective in mitigating several long-term adverse outcomes, such as CVD and death, in the general population with subclinical hypothyroidism.12”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [12]
This recommendation has been followed by 2 recent comprehensive reviews that summarized the evidence arguing against clinical benefits of thyroid hormone replacement therapy toward quality of life or hypothyroid symptoms among adults, especially elderly individuals, with subclinical hypothyroidism.
“This recommendation has been followed by 2 recent comprehensive reviews1,12 that summarized the evidence arguing against clinical benefits of thyroid hormone replacement therapy toward quality of life or hypothyroid symptoms among adults, especially elderly individuals, with subclinical hypothyroidism.”
From Association of subclinical hypothyroidism and cardiovascular disease with mortality (2020) · cites this paper as [12]
Another international expert group concluded that few patients with subclinical hypothyroidism would be likely to benefit from treatment with LT4.
“Another international expert group concluded that few patients with subclinical hypothyroidism would be likely to benefit from treatment with LT4”
From Pharmacodynamic and Therapeutic Actions of Levothyroxine (2021) · cites this paper as [131]
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References 28 · Cited by 240
- Authors
- Bekkering, G. E., Agoritsas, T., Lytvyn, L., Heen, A. F., Feller, M., Moutzouri, E., Abdulazeem, H., Aertgeerts, B., Beecher, D., Brito, J. P., Farhoumand, P. D., Singh Ospina, N., Rodondi, N., van Driel, M., Wallace, E., Snel, M., Okwen, P. M., Siemieniuk, R., Vandvik, P. O., Kuijpers, T., & Vermandere, M.
- Affiliations
- KU Leuven (BE)
- McMaster University (CA)
- Innlandet Hospital Trust (NO)
- University of Bern (CH)
- Mayo Clinic (US)
- University Hospital of Geneva (CH)
- Royal College of Surgeons in Ireland (IE)
- Leiden University Medical Center (NL)
- Effective Basic Services for Africa (CM)
- Norwegian Institute of Public Health (NO)
- Dutch College of General Practitioners (NL)
- Corresponding author
- Bekkering, G E
- ORCID
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2019-05-14
- Volume
- 365
- Pages
- l2006
- ISSN
- 1756-1833 (ISSN-L)
- 0959-8138
- OpenAlex
- W2945825315
- Cited by
- 240
- References
- 28
- Citations by year
- 2026: 19 · 2025: 27 · 2024: 27 · 2023: 43 · 2022: 36 · 2021: 38 · 2020: 38 · 2019: 12
- FWCI
- 25.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Lirias (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Bern Open Repository and Information System (University of Bern) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- subclinical hypothyroidism, thyroid hormone replacement, levothyroxine, thyroid-stimulating hormone, free thyroxine, treatment risks and benefits, cardiovascular events, mortality, quality of life, depressive symptoms, shared decision-making
- MeSH terms
- Adult, Aged, Decision Making, Decision Support Techniques, Depression, Fatigue, Female, Humans, Hypothyroidism, Quality of Life, Thyroid Hormones, Thyrotropin, Thyroxine, Body Mass Index, Uncertainty
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