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Original Investigation
October 30, 2019

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

Author Affiliations
  • 1Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands
  • 2Institute for Evidence-Based Medicine in Old Age, Leiden, the Netherlands
  • 3Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands
  • 4Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
  • 5School of Public Health, University College Cork, Cork, Ireland
  • 6Department of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
  • 7Institute of Primary Health Care (BIHAM), University of Bern, Bern, Switzerland
  • 8Department of Public Health, University of Copenhagen, Copenhagen, Denmark
  • 9Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
  • 10Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, the Netherlands
  • 11Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands
  • 12Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, the Netherlands
  • 13Robertson Centre for Biostatistics, University of Glasgow, Glasgow, United Kingdom
  • 14Division of Epidemiology, Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California
  • 15Service of Endocrinology, Diabetes and Metabolism, Lausanne University Hospital, Lausanne, Switzerland
  • 16Department of Internal Medicine, Copenhagen University Hospital Herlev, Gentofte, Denmark
  • 17Department of Endocrinology and Metabolic Disorders, Leiden University Medical Center, Leiden, the Netherlands
  • 18Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
  • 19Radboud University Medical Center, Nijmegen, the Netherlands
  • 20Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
JAMA. 2019;322(20):1977-1986. doi:10.1001/jama.2019.17274
Key Points

Question  Among adults aged 80 years and older with subclinical hypothyroidism, what is the association between treatment with levothyroxine and thyroid-related symptoms?

Findings  In this pooled analysis of data from 2 randomized clinical trials that included 251 participants aged 80 years and older, treatment with levothyroxine, compared with placebo, was not significantly associated with improvement in thyroid-related patient-reported quality of life outcome scores (range, 0-100; higher scores indicate worse quality of life; minimal clinically important difference, 9) for hypothyroid symptoms (adjusted between-group difference, 1.3) or tiredness (adjusted between-group difference, 0.1).

Meaning  These findings do not support routine treatment with levothyroxine for subclinical hypothyroidism in adults aged 80 years and older.

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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