Sex-specific associations between obstructive sleep apnea and thyroid hormone sensitivity in euthyroid adults

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BACKGROUND: The relationship between obstructive sleep apnea (OSA) and thyroid hormone sensitivity remains unclear. Thyroid hormone sensitivity indices may reveal subclinical hypothalamic-pituitary-thyroid (HPT) axis dysregulation beyond conventional hormone levels. METHODS: We analyzed 718 euthyroid adults who underwent overnight sleep monitoring, using thyroid‑stimulating hormone index (TSHI), thyroid feedback quantile-based index (TFQI), parametric thyroid feedback quantile-based index (PTFQI), thyrotroph T4 resistance index (TT4RI), thyrotroph T3 resistance index (TT3RI) and the ratio of free triiodothyronine to free thyroxine (FT3/FT4 ratio) to assess central and peripheral thyroid hormone sensitivity. Analysis of covariance assessed differences across OSA severity after adjusting for age and BMI. Multivariable linear regression examined associations between OSA severity and thyroid hormone sensitivity indices in sex-stratified models. Correlations between OSA-related parameters and thyroid hormones sensitivity indices were further explored using quadratic prediction plots. RESULTS: Among females, OSA patients showed higher FT4 and significantly increased TFQI, PTFQI, TSHI, and TT4RI, but lower FT3/FT4 ratio compared with non-OSA. TFQI (P for trend = 0.0395) and TT4RI (P for trend = 0.0293) were positively correlated with increasing OSA severity. OSA was independently associated with elevated TFQI (β = 0.26, 95% CI 0.010-0.42, P = 0.001), PTFQI (β = 0.20, 95% CI 0.05-0.35, P = 0.011), TSHI (β = 0.24, 95% CI 0.03-0.44, P = 0.025), and TT4RI (β = 6.82, 95% CI 0.59-13.05, P = 0.033). apnea-hypopnea index (AHI), oxygen desaturation index (ODI) were significantly correlated with TT4RI (P = 0.034, 0.021, respectively). No significant associations were observed in males. CONCLUSIONS: OSA is associated with impaired central and peripheral thyroid hormone sensitivity in euthyroid females, but not in males.

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