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.
Conflict of interest statement
Study Protocol: A Randomised Controlled Trial on the Clinical Effects of Levothyroxine Treatment for Subclinical Hypothyroidism in People Aged 80 Years and OverRS Du Puy et al. BMC Endocr Disord 18 (1), 67. PMID 30231866. - Randomized Controlled TrialNederlands (Dutch) Trial Register: NTR3851 (12-02-2013), EudraCT: 2012-004160-22 (17-02-2013), ABR-41259.058.13 (12-02-2013).
Thyroid Hormone Therapy for Older Adults With Subclinical HypothyroidismDJ Stott et al. N Engl J Med 376 (26), 2534-2544. PMID 28402245. - Randomized Controlled TrialLevothyroxine provided no apparent benefits in older persons with subclinical hypothyroidism. (Funded by European Union FP7 and others; TRUST ClinicalTrials.gov number, N …
Study Protocol; Thyroid Hormone Replacement for Untreated Older Adults With Subclinical Hypothyroidism - A Randomised Placebo Controlled Trial (TRUST)DJ Stott et al. BMC Endocr Disord 17 (1), 6. PMID 28158982. - Randomized Controlled TrialClinicaltrials.gov NCT01660126 ; registered 8th June 2012.
Interventions for Clinical and Subclinical Hypothyroidism in PregnancySM Reid et al. Cochrane Database Syst Rev (7), CD007752. PMID 20614463. - ReviewLevothyroxine treatment of clinical hypothyroidism in pregnancy is already standard practice given the documented benefits from earlier non-randomised studies. Whether le …
Levothyroxine to Increase Live Births in Euthyroid Women With Thyroid Antibodies Trying to Conceive: The TABLET RCTRK Dhillon-Smith et al. PMID 31617987. - ReviewLevothyroxine therapy in a dose of 50 µg per day does not improve live birth rate in euthyroid women with thyroid peroxidase antibodies.
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