Measuring Hypothyroidism Disease Control Using a TSH-based "Time-in-range"

Time-in-range (TIR) using sequential TSH levels during levothyroxine (LT4) treatment could serve as a measure of chronic disease control in hypothyroidism.

Primary objectives: (1) develop a method of estimating TIR and (2) determine the impact of patient sociodemographic characteristics on TIR. Secondary objective: investigate the relationship between TIR and time to cardiovascular event.

The study was conducted using longitudinal clinical data (2016-2022) from a single academic institution. Study participants were ≥18 years old, LT4-treated, and had ≥3 unique TSH levels collected over a minimum of 2 years. For each patient, TIR, time-above-range (TAR) and time-below-range (TBR) were estimated using linear interpolation of log-transformed TSH levels. Fitted linear regression was used to evaluate the relationship between TIR/TAR/TBR and LT4 dose over the study period. Generalized estimating equations were used to model annualized TIR/TAR/TBR with sociodemographic and clinical covariates. Survival analysis was used to characterize the relationship between TIR and occurrence of cardiovascular events.

A total of 2752 LT4-treated patients had a median TIR of 86% over the study enrollment period (median, 3.8 years). For both males and females, LT4 dose was negatively correlated with TIR (R = -0.23 and -0.30, respectively; P < .001 for both). Male sex and Black race were associated with TIR <75% (OR, 1.30; P < .001; OR, 1.37; P < .001). The association between TAR and cardiovascular events approached significance (OR, 1.03 per +10% TAR; P = .078).

We used TIR estimation to identify differences in disease control between sociodemographic groups and the impact of LT4 dose. In future studies, we aim to better characterize the association between TIR and clinically meaningful outcomes.