Effect of Thyroid Hormone Therapy on Fatigability in Older Adults With Subclinical Hypothyroidism: A Nested Study Within a Randomized Placebo-Controlled Trial

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.

Effect of Levothyroxine on Older Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis

“…About 5000 participants were included in the meta-analysis and systematic review, all of whom were over 60 years of age. Individuals in the Stuber’s study ( 15 ) were all from the Stott’s study and had no new findings, so Stuber’s study were excluded. Individuals in the Gencer’s ( 18 ), Wildisen’s ( 16 ) and Gonzalez Rodriguez’s ( 12 ) studies, although also all from the Stott’s study, were continued to be included because these three articles analyzed different results.…”

“…Whether levothyroxine can provide benefit to older patients with SCH has been explored in several studies. Most studies did not find a significant effect of levothyroxine on older patients with SCH, such as bone density ( 11 , 12 ), hypothyroidism symptoms and fatigue ( 13 – 15 ), depressive symptoms ( 16 ), cognitive function ( 17 ), cardiac function ( 18 ), ischemic heart disease ( 19 ), cardiovascular outcomes ( 20 ). However, a study ( 21 ) comparing old and young patients with SCH found that levothyroxine was effective in improving the quality of life of old patients.…”

Severity of Fatigue and Its Relationship with TSH before and after Levothyroxine Replacement Therapy in Patients with Primary Hypothyroidism

“…Regarding disease etiology, one study demonstrated that fatigue and fatigue-related symptoms in hypothyroidism were more pronounced in patients with autoimmune diseases compared to patients with differentiated thyroid carcinoma, which was reflected in significantly higher scores on the MFI-20 questionnaire; however, these results could not be associated with thyroid hormone parameters [ 6 ]. Autoimmunity has been shown to have an impact on the quality of life of patients with autoimmune hypothyroidism, especially in terms of psychological symptoms; however, its direct association with fatigue has been unclear [ 13 ]. Despite these data, in our study, no differences in the FSS score were observed when comparing patients with autoimmune hypothyroidism versus unspecified hypothyroidism; similarly, no association was found between the fatigue severity scale score and the presence of autoimmune disease or TPOAb and TgAb levels.…”

Genome‑wide profiling of DNA methylation and gene expression unravel the epigenetic landscape in diabetes-related hypothyroidism

“…T2DM and hypothyroidism have similar clinical symptoms, such as fatigue, edema, paleness, and weight gain [ 1 , 16 – 18 ]. Therefore, the symptoms of T2DM can mask the occurrence of hypothyroidism.…”

“…Low T3 and T4 levels were detected in Nthy-ori3-1 cells incubated in highglucose medium. T2DM and hypothyroidism have similar clinical symptoms, such as fatigue, edema, paleness, and weight gain [1,[16][17][18]. Therefore, the symptoms of T2DM can mask the occurrence of hypothyroidism.…”