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Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis

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Feller, Martin, Snel, Marieke, Moutzouri, Elisavet, Bauer, Douglas C., de Montmollin, Maria, Aujesky, Drahomir, Ford, Ian, Gussekloo, Jacobijn +7 more·2018·JAMA
DOI 10.1001/jama.2018.13770PMC PMC6233842
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Abstract

Importance: The benefit of thyroid hormone therapy for subclinical hypothyroidism is uncertain. New evidence from recent large randomized clinical trials warrants an update of previous meta-analyses. Objective: To conduct a meta-analysis of the association of thyroid hormone therapy with quality of life and thyroid-related symptoms in adults with subclinical hypothyroidism. Data Sources: PubMed, EMBASE, ClinicalTrials.gov, Web of Science, Cochrane Library, CENTRAL, Emcare, and Academic Search Premier from inception until July 4, 2018. Study Selection: Randomized clinical trials that compared thyroid hormone therapy with placebo or no therapy in nonpregnant adults with subclinical hypothyroidism were eligible. Two reviewers independently evaluated eligibility based on titles and abstracts of all retrieved studies. Studies not excluded in this first step were independently assessed for inclusion after full-text evaluation by 2 reviewers. Data Extraction and Synthesis: Two independent reviewers extracted data, assessed risk of bias (Cochrane risk-of-bias tool), and evaluated the quality of evidence (GRADE tool). For synthesis, differences in clinical scores were transformed (eg, quality of life) into standardized mean differences (SMDs; positive values indicate benefit of thyroid hormone therapy; 0.2, 0.5, and 0.8 correspond to small, moderate, and large effects, respectively). Random-effects models for meta-analyses were applied. Main Outcomes and Measures: General quality of life and thyroid-related symptoms after a minimum follow-up of 3 months. Results: Overall, 21 of 3088 initially identified publications met the inclusion criteria, with 2192 adults randomized. After treatment (range, 3-18 months), thyroid hormone therapy was associated with lowering the mean thyrotropin value into the normal reference range compared with placebo (range, 0.5-3.7 mIU/L vs 4.6 to 14.7 mIU/L) but was not associated with benefit regarding general quality of life (n = 796; SMD, -0.11; 95% CI, -0.25 to 0.03; I2=66.7%) or thyroid-related symptoms (n = 858; SMD, 0.01; 95% CI, -0.12 to 0.14; I2=0.0%). Overall, risk of bias was low and the quality of evidence assessed with the GRADE tool was judged moderate to high. Conclusions and Relevance: Among nonpregnant adults with subclinical hypothyroidism, the use of thyroid hormone therapy was not associated with improvements in general quality of life or thyroid-related symptoms. These findings do not support the routine use of thyroid hormone therapy in adults with subclinical hypothyroidism.

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  • Large RCTs have shown no improvement in hypothyroid symptoms or quality of life in older patients with subclinical hypothyroidism during treatment with levothyroxine.

    “large RCTs have shown no improvement in hypothyroid symptoms or quality of life (QoL) in older patients with subclinical hypothyroidism during treatment with levothyroxine. 15 -17”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [17]

  • Treatment of subclinical hypothyroidism does not improve clinical symptoms such as overweight.

    “This advice will prevent dissatisfaction with the outcome of LT4 treatment, as a recent meta-analysis showed that treatment of subclinical hypothyroidism does not improve clinical symptoms such as overweight [52].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [52]

  • A meta-analysis among nonpregnant adults with subclinical hypothyroidism showed the use of thyroid hormone therapy was not associated with improvements in general QoL or thyroid-related symptoms.

    “A meta-analysis among nonpregnant adults with subclinical hypothyroidism showed the use of thyroid hormone therapy was not associated with improvements in general QoL or thyroid-related symptoms [52].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [52]

  • Treatment of subclinical hypothyroidism is unlikely to improve symptoms in patients initially treated because of subclinical hypothyroidism.

    “I would exclude patients who initially were treated because of subclinical hypothyroidism, as treatment is unlikely to improve their symptoms [52].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [52]

  • The use of thyroid hormone in subclinical hypothyroidism is not associated with improvements in QoL or thyroid-related symptoms.

    “More recently, it has become clear from placebo-controlled RCTs that the use of thyroid hormone in subclinical hypothyroidism is not associated with improvements in QoL or thyroid-related symptoms [52].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [52]

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Research works printed but not linked: 1

  1. Cochrane Effective Practice and Organisation of Care. Data collection form: EPOC resources for review authors. Oslo: Norwegian Knowledge Centre for the Health Services; 2017. https://epoc.cochrane .org/sites/epoc.cochrane.org/files/public/uploads /Resources-for-authors2017/good_practice_data _extraction_form.doc. Accessed July 6, 2018.

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Authors
Feller, M., Snel, M., Moutzouri, E., Bauer, D. C., de Montmollin, M., Aujesky, D., Ford, I., Gussekloo, J., Kearney, P. M., Mooijaart, S., Quinn, T., Stott, D., Westendorp, R., Rodondi, N., & Dekkers, O. M.
Affiliations
  • University of Bern (CH)
  • Leiden University (NL)
  • University of California, San Francisco (US)
  • Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • University of Glasgow (GB)
  • University College Cork (IE)
  • University of Copenhagen (DK)
Corresponding author
Feller, Martin
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2018-10-02
Volume
320
Issue
13
Pages
1349
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2018.13770
PMC
PMC6233842
OpenAlex
W2894730508
Cited by
266
References
67
Citations by year
2026: 22 · 2025: 28 · 2024: 23 · 2023: 42 · 2022: 32 · 2021: 42 · 2020: 42 · 2019: 31 · 2018: 4
FWCI
4.58
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
Funders
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (172676)
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, quality of life, thyroid-stimulating hormone, TSH normalization, adults, risk of bias, quality of evidence, GRADE, standardized mean difference, risk of bias assessment
MeSH terms
Adult, Blood Pressure, Humans, Hypothyroidism, Quality of Life, Thyrotropin, Thyroxine, Practice Guidelines as Topic

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