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Cited by 121Thyroid Disorders and TreatmentsThyroid and Parathyroid SurgeryHormonal and reproductive studies

Association Between Levothyroxine Treatment and Thyroid-Related Symptoms Among Adults Aged 80 Years and Older With Subclinical Hypothyroidism

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Mooijaart, Simon P., Du Puy, Robert S., Stott, David J., Kearney, Patricia M., Rodondi, Nicolas, Westendorp, Rudi G. J., den Elzen, Wendy P. J., Postmus, Iris +15 more·2019·JAMA
DOI 10.1001/jama.2019.17274PMC PMC6822162
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Abstract

IMPORTANCE: It is unclear whether levothyroxine treatment provides clinically important benefits in adults aged 80 years and older with subclinical hypothyroidism. OBJECTIVE: To determine the association of levothyroxine treatment for subclinical hypothyroidism with thyroid-related quality of life in adults aged 80 years and older. DESIGN, SETTING, AND PARTICIPANTS: Prospectively planned combined analysis of data involving community-dwelling adults aged 80 years and older with subclinical hypothyroidism. Data from a randomized clinical trial were combined with a subgroup of participants aged 80 years and older from a second clinical trial. The trials were conducted between April 2013 and May 2018. Final follow-up was May 4, 2018. EXPOSURES: Participants were randomly assigned to receive levothyroxine (n = 112; 52 participants from the first trial and 60 from the second trial) or placebo (n = 139; 53 participants from the first trial and 86 from the second trial). MAIN OUTCOMES AND MEASURES: Co-primary outcomes were Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire scores for the domains of hypothyroid symptoms and tiredness at 1 year (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9). RESULTS: Of 251 participants (mean age, 85 years; 118 [47%] women), 105 were included from the first clinical trial and 146 were included from the second clinical trial. A total of 212 participants (84%) completed the study. The hypothyroid symptoms score decreased from 21.7 at baseline to 19.3 at 12 months in the levothyroxine group vs from 19.8 at baseline to 17.4 at 12 months in the placebo group (adjusted between-group difference, 1.3 [95% CI, -2.7 to 5.2]; P = .53). The tiredness score increased from 25.5 at baseline to 28.2 at 12 months in the levothyroxine group vs from 25.1 at baseline to 28.7 at 12 months in the placebo group (adjusted between-group difference, -0.1 [95% CI, -4.5 to 4.3]; P = .96). At least 1 adverse event occurred in 33 participants (29.5%) in the levothyroxine group (the most common adverse event was cerebrovascular accident, which occurred in 3 participants [2.2%]) and 40 participants (28.8%) in the placebo group (the most common adverse event was pneumonia, which occurred in 4 [3.6%] participants). CONCLUSIONS AND RELEVANCE: In this prospectively planned analysis of data from 2 clinical trials involving adults aged 80 years and older with subclinical hypothyroidism, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in hypothyroid symptoms or fatigue. These findings do not support routine use of levothyroxine for treatment of subclinical hypothyroidism in adults aged 80 years and older. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01660126; Netherlands Trial Register: NTR3851.

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  • Later studies among adults aged 80 years and older with subclinical hypothyroidism confirmed that LT4 treatment, compared to placebo, was not significantly associated with improvement in hypothyroid symptoms, fatigue, or depressive symptoms.

    “Later studies among adults aged 80 years and older with subclinical hypothyroidism confirmed that LT4 treatment, compared to placebo, was not significantly associated with improvement in hypothyroid symptoms, fatigue, or depressive symptoms [53,54].”

    From T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity (2021) · cites this paper as [53]

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  • No clear advantages of treating subclinical hypothyroidism in older individuals (>65 years) have been observed in terms of neurocognitive function and quality of life.

    “No clear advantages of treating subclinical hypothyroidism in older individuals (>65 years) have been observed in terms of neurocognitive function and quality of life, 146-148”

    From Hypothyroidism (2024) · cites this paper as [146]

  • 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 [16]

  • Trials do not show a benefit from thyroid hormone replacement in persistent subclinical hypothyroidism.

    “or to those with persistent subclinical hypothyroidism, where trials do not show a benefit from thyroid hormone replacement. 12,15,16,44 -46”

    From Use of liothyronine (T3) in hypothyroidism: Joint British Thyroid Association/Society for endocrinology consensus statement (2023) · cites this paper as [16]

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Authors
Mooijaart, S. P., Du Puy, R. S., Stott, D. J., Kearney, P. M., Rodondi, N., Westendorp, R. G. J., den Elzen, W. P. J., Postmus, I., Poortvliet, R. K. E., van Heemst, D., van Munster, B. C., Peeters, R. P., Ford, I., Kean, S., Messow, C.-M., Blum, M. R., Collet, T.-H., Watt, T., Dekkers, O. M., Jukema, J. W., Smit, J. W. A., Langhorne, P., & Gussekloo, J.
Affiliations
  • Leiden University Medical Center (NL)
  • Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands
  • University of Glasgow (GB)
  • University College Cork (IE)
  • University of Bern (CH)
  • University of Copenhagen (DK)
  • Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
  • Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
  • Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands
  • Erasmus MC (NL)
  • Centre Hospitalier Universitaire Vaudois (CH)
  • Herlev Hospital (DK)
  • Radboud University Medical Center (NL)
Corresponding author
Mooijaart, Simon P.
ORCID
Venue
JAMA
Publisher
American Medical Association (AMA)
Published
2019-11-26
Volume
322
Issue
20
Pages
1977
ISSN
  • 0002-9955 (ISSN-L)
  • 0098-7484
DOI
10.1001/jama.2019.17274
PMC
PMC6822162
OpenAlex
W2982419362
Cited by
121
References
33
Citations by year
2026: 12 · 2025: 6 · 2024: 20 · 2023: 18 · 2022: 18 · 2021: 21 · 2020: 24 · 2019: 2
FWCI
13.18
Type
journal article
Language
en
Open access
Locations
  • JAMA (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
  • Archive ouverte UNIGE (University of Geneva) (publishedVersion)
  • Pure Amsterdam UMC (acceptedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
  • ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
  • IRIS (submittedVersion)
  • SERVAL (Université de Lausanne) (submittedVersion)
  • Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc-nd)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
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 › Hormonal and reproductive studies
Keywords
levothyroxine, subclinical hypothyroidism, older adults, fatigue, thyroid hormone replacement, community-dwelling adults, subgroup analysis, randomized controlled trials

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