No Effect of Levothyroxine on Hemoglobin in Older Adults With Subclinical Hypothyroidism: Pooled Results From 2 Randomized Controlled Trials

Robert S Du Puy, Rosalinde K E Poortvliet, Simon P Mooijaart, David J Stott, Terry Quinn, Naveed Sattar, Rudi G J Westendorp, Patricia M Kearney, Vera J C McCarthy, Stephen Byrne, Nicolas Rodondi, Oliver Baretella, Tinh-Hai Collet, Diana van Heemst, Olaf M Dekkers, J Wouter Jukema, Johannes W A Smit, Jacobijn Gussekloo, Wendy P J den Elzen, Robert S Du Puy, Rosalinde K E Poortvliet, Simon P Mooijaart, David J Stott, Terry Quinn, Naveed Sattar, Rudi G J Westendorp, Patricia M Kearney, Vera J C McCarthy, Stephen Byrne, Nicolas Rodondi, Oliver Baretella, Tinh-Hai Collet, Diana van Heemst, Olaf M Dekkers, J Wouter Jukema, Johannes W A Smit, Jacobijn Gussekloo, Wendy P J den Elzen

Abstract

Context: Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age.

Objective: The aim of this study was to assess whether levothyroxine treatment leads to a rise in hemoglobin levels in older persons with subclinical hypothyroidism.

Methods: This preplanned combined analysis of 2 randomized controlled trials included community-dwelling persons aged 65 years and older with subclinical hypothyroidism who were randomly assigned to levothyroxine or placebo treatment. The levothyroxine dose was periodically titrated aiming at thyroid stimulating hormone (TSH) level within the reference range, with mock titrations in the placebo group. The main outcome measure was the change in hemoglobin level after 12 months.

Results: Analyses included 669 participants (placebo n = 337, levothyroxine n = 332) with a median age of 75 years (range, 65-97) and mean baseline hemoglobin of 13.8 ± 1.3 g/dL. Although levothyroxine treatment resulted in a reduction in TSH from baseline after 12 months of follow-up compared with placebo, the change in hemoglobin level was not different between the levothyroxine and the placebo groups (-0.03 g/dL [95% CI, -0.16 to 0.11]). Similar results were found in stratified analyses including sex, age, or TSH levels. No difference in change of hemoglobin levels after 12 months was identified in 69 participants with anemia at baseline (-0.33 g/dL [95% CI, -0.87 to 0.21]).

Conclusion: In persons aged 65 years and older with subclinical hypothyroidism, treatment with levothyroxine does not lead to a rise in hemoglobin levels, regardless of the presence of anemia.

Trial registration: ClinicalTrials.gov NCT01660126.

Keywords: RCT; anemia; older adults; subclinical hypothyroidism; thyroid.

© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Recruitment, randomization, and patient flow of the participants.
Figure 2.
Figure 2.
Baseline Hb levels per quartiles of TSH and fT4. Boxplots represent the median, interquartile range, minimum, and maximum in Hb levels per quartile of TSH (mIU/L) and fT4 (pmol/L). Difference in medians were evaluated using the Kruskal-Wallis test.
Figure 3.
Figure 3.
Levothyroxine treatment effect on Hb levels after 12 months of treatment. Boxplots represent the median, interquartile range, minimum, and maximum in Hb levels. Treatment effect −0.03 g/dL (95% CI, −0.16 to 0.11). Treatment effect (95% CI) was calculated using linear mixed effect regression models adjusting for study site, study, treatment dose at randomization, age, and sex and represents the additional change in hemoglobin level after 12 months of treatment with levothyroxine, compared with placebo.

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Source: PubMed

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