Effect of thyroid hormone therapy on fatigability in older adults with subclinical hypothyroidism: a nested study within a randomized placebo-controlled trial

Stuber, M. J. et al. (2020) Effect of thyroid hormone therapy on fatigability in older adults with subclinical hypothyroidism: a nested study within a randomized placebo-controlled trial. Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 75(9), e89-e94. (doi: 10.1093/gerona/glaa123) (PMID:32577745) (PMCID:PMC7494024)

Abstract

Background: Fatigue often triggers screening for and treatment of subclinical hypothyroidism. However, data on the impact of levothyroxine on fatigue is limited and previous studies might not have captured all aspects of fatigue. Method: This study is nested within the randomized, placebo-controlled, multicenter TRUST trial, including community-dwelling participants aged ≥65 and older, with persistent subclinical hypothyroidism (TSH 4.60–19.99 mIU/L, normal free thyroxine levels) from Switzerland and Ireland. Interventions consisted of daily levothyroxine starting with 50 μg (25 μg if weight <50 kg or known coronary heart diseases) together with dose adjustments to achieve a normal TSH and mock titration in the placebo group. Main outcome was the change in physical and mental fatigability using the Pittsburgh Fatigability Scale over 1 year, assessed through multivariable linear regression with adjustment for country, sex, and levothyroxine starting dose. Results: Among 230 participants, the mean ± standard deviation (SD) TSH was 6.2 ± 1.9 mIU/L at baseline and decreased to 3.1 ± 1.3 with LT4 (n = 119) versus 5.3 ± 2.3 with placebo (n = 111, p < .001) after 1 year. After adjustment we found no between-group difference at 1 year on perceived physical (0.2; 95% CI −1.8 to 2.1; p = .88), or mental fatigability (−1.0; 95% CI −2.8 to 0.8; p = .26). In participants with higher fatigability at baseline (≥15 points for the physical score [n = 88] or ≥13 points for the mental score [n = 41]), the adjusted between-group differences at 1 year were 0.4 (95% CI −3.6 to 2.8, p = .79) and −2.2 (95% CI −8.8 to 4.5, p = .51). Conclusions: Levothyroxine in older adults with mild subclinical hypothyroidism provides no change in physical or mental fatigability.

• Item Type: Articles
• Additional Information: This nested study on fatigability within the TRUST trial was funded by a grant from the Swiss National Science Foundation (SNSF 320030-172676 to N.R.). The TRUST Thyroid trial was supported by research grant (278148) from the European Union FP7-HEALTH-2011 program and by grants from the Swiss National Science Foundation (SNSF 320030-150025 and 320030-172676 to N.R.) and the Swiss Heart Foundation and Velux Stiftung (grant 974a to N.R). M.R.B’s work was supported by a grant from the Swiss National Science Foundation (P2BEP3_175289). T-H.C.’s research is supported by grants from the Swiss National Science Foundation (PZ00P3-167826). The study medication (levothyroxine and matching placebo) was supplied free of charge by Merck KGaA, Darmstadt, Germany. Merck played no role in the design, analysis, or reporting of the trial. The main TRUST sponsor (NHS Greater Glasgow and Clyde Health Board) contributed to the writing of the protocol.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott J, Professor David
• Authors: Stuber, M. J., Moutzouri, E., Feller, M., Del Giovane, C., Bauer, D. C., Blum, M. R., Collet, T.-H., Gussekloo, J., Mooijaart, S. P., McCarthy, V. J.C., Aujesky, D., Westendorp, R., Stott, D. J., Glynn, N. W., Kearney, P. M., and Rodondi, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journals of Gerontology Series A: Biological Sciences and Medical Sciences
• Publisher: Oxford University Press
• ISSN: 1079-5006
• ISSN (Online): 1758-535X
• Published Online: 06 June 2020
• Copyright Holders: Copyright © 2020 The Authors
• First Published: First published in Journals of Gerontology Series A: Biological Sciences and Medical Sciences 75(9): e89-e94
• Publisher Policy: Reproduced under a Creative Commons License