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

Disclosures

J Clin Endocrinol Metab. 2022;107(6):e2339-e2347. 

In This Article

Abstract and Introduction

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.

Introduction

Subclinical thyroid dysfunction and anemia are common disorders, and both have increasing prevalence with advancing age.[1–4] The symptoms of both subclinical hypothyroidism and anemia are frequently nonspecific and of similar nature (e.g., fatigue, malaise, shortness of breath, and exercise intolerance).

A number of studies have suggested a potential causal relationship between thyroid dysfunction and hematopoiesis.[5–8] Lower hemoglobin levels have been observed in persons with (subclinical) hypothyroidism compared with their euthyroid counterparts and small cohort studies have shown increases in hemoglobin and erythropoietin levels after treatment of overt hypothyroidism.[8–17]

We reported earlier the results of an individual participant data meta-analysis using data from 16 independent observational cohort studies including more than 42 000 participants. In participants with both overt and subclinical hypothyroidism, we demonstrated a higher anemia prevalence.[18] In addition, reduced thyroid function at baseline was associated with an increased risk of anemia during follow-up. To date, however, there is a lack of experimental evidence of the effect of levothyroxine treatment on hemoglobin levels in older persons with subclinical hypothyroidism.

The aim of this study was to assess whether levothyroxine treatment for subclinical hypothyroidism leads to a rise in hemoglobin levels in older persons. We performed a preplanned secondary outcome analysis of 2 randomized controlled trials on levothyroxine treatment for subclinical hypothyroidism in older persons.

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