Subclinical hyperthyroidism is associated with reduced spirometric parameters in asymptomatic adults: a...

The pulmonary effects of subclinical hyperthyroidism (SH) remain incompletely understood, and previous studies have been limited by reliance on absolute spirometric values, absence of etiology stratification, and inadequate control for anthropometric confounders. This cross-sectional study evaluated whether biochemically confirmed SH is independently associated with reduced spirometric parameters in asymptomatic adults, and whether these associations differ by SH etiology.

A total of 148 outpatients aged 18-65 years were enrolled: 101 with confirmed SH (TSH < 0.4 mIU/L on two independent measurements ≥3 months apart, with normal fT4 and fT3) and 47 euthyroid controls (TSH 0.4-4.0 mIU/L). Individuals with pulmonary disease, cardiovascular disease, neuromuscular disorders, smoking history, or recent respiratory infection were excluded. Spirometry was performed according to ATS/ERS 2019 standards and results expressed as percent predicted (%pred) using European Community for Steel and Coal (ECSC) 1993 reference equations. To address demographic imbalances, a 1:1 age- and sex-matched sensitivity analysis (n = 34 per group) was performed. Multivariate linear regression controlled for age, sex, BMI, and height. SH etiology (Graves' disease, toxic multinodular goiter [TMNG], autonomous nodule, exogenous) and TSH suppression grade (Grade 1: 0.1-0.4 mIU/L; Grade 2: <0.1 mIU/L) were recorded RESULTS: In the full study population, SH was associated with significantly lower FVC%pred (90.2 ± 22.9 vs. 104.9 ± 16.0, p < 0.001), FEV₁%pred (p < 0.001), PEF%pred (p = 0.004), and FEF₂₅-₇₅%pred (p = 0.006). The FEV₁/FVC ratio did not differ between groups (p = 0.670). A restrictive spirometric pattern was more prevalent in SH patients than controls (19% vs. 4%, p = 0.035). In the matched sample, FVC%pred (97.8 ± 15.6 vs. 106.8 ± 15.2, p = 0.018) and FEV₁%pred (95.4 ± 16.2 vs. 103.2 ± 15.8, p = 0.049) remained significantly lower. Multivariate regression confirmed SH as an independent correlate of lower FVC%pred (β = -7.09, 95% CI: -14.17 to -0.02, p = 0.049). Etiology-stratified analysis revealed that spirometric impairment was driven primarily by TMNG (FVC%pred 85.0 vs. 104.2 in controls, p < 0.001; FEV₁%pred 78.5 vs. 103.0 in controls, p < 0.001), whereas Graves' disease and autonomous nodule patients did not differ significantly from controls. Confirmatory TSH measurements demonstrated high temporal consistency (Spearman p = 0.960, p < 0.001), with 99/101 patients classified as persistent SH.

In this cross-sectional study, confirmed SH was independently associated with modest but statistically significant reductions in spirometric parameters, with the impairment concentrated in patients with TMNG etiology. As causal inference is not possible from a cross-sectional design, these findings should be regarded as hypothesis-generating. They support etiology-specific respiratory evaluation in selected SH patients and highlight the priority of longitudinal intervention studies to determine whether restoration of euthyroidism normalizes spirometric parameters.