Thyroid function status in patients with hypothyroidism on thyroxine replacement and associated factors: a retrospective cohort study in primary care.

After two-year follow-up, 61.9% of subjects with hypothyroidism on thyroxine replacement were euthyroid, while 29.5% were under-replaced and 8.6% were over-replaced.

• Data from 5,749 eligible subjects were analyzed (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese).
• Euthyroid status was defined as TSH 0.65–3.70 mIU/L; under-replacement as TSH ≥ 3.70 mIU/L; over-replacement as TSH ≤ 0.65 mIU/L.
• 3,558 subjects were euthyroid, 1,694 were under-replaced, and 497 were over-replaced at two-year follow-up.
• Thyroid status did not differ significantly with various dose regimens (daily, segmented, or alternate days) (p = 0.193).

Male gender was significantly associated with thyroxine under-replacement.

• Stepwise logistic regression identified male gender as a significant factor: AOR = 1.25, 95% CI = 1.03–1.51, p = 0.02.
• This finding was derived from a cohort that was 79% female, meaning male patients represented a minority but showed higher odds of under-replacement.
• The analysis controlled for other demographic and clinical variables in the stepwise logistic regression model.

Obesity was significantly associated with thyroxine under-replacement.

• Stepwise logistic regression showed AOR = 1.34, 95% CI = 1.08–1.66, p = 0.008 for obesity.
• Obesity was identified alongside male gender as a key factor associated with suboptimal thyroid control (under-replacement).
• These associations were identified through stepwise logistic regression analysis of demographic and clinical data.

Every unit increase in mean daily thyroxine dose (μg/kg body weight) was associated with 2.72 times greater odds of over-replacement.

• The association was identified via stepwise logistic regression analysis.
• Dose was expressed per unit of μg/kg body weight.
• This finding highlights weight-based dosing as a critical factor in avoiding over-replacement.

Monitoring thyroid function at intervals of ≤12 months was less likely to detect both under-replacement and over-replacement compared to monitoring at 13–24 month intervals.

• Shorter interval monitoring (≤12 months) was less likely to detect under-replacement: AOR = 0.57, 95% CI = 0.44–0.74, p < 0.001.
• Shorter interval monitoring was also less likely to detect over-replacement: AOR = 0.62, 95% CI = 0.41–0.97, p = 0.033.
• The reference interval for comparison was 13–24 months.
• These findings suggest that shorter monitoring intervals may capture patients before thyroid status has shifted sufficiently to be detected as abnormal.

Among patients who were euthyroid at baseline, the cumulative proportion developing suboptimal thyroid control increased substantially over time.

• Among 3,312 adults who were euthyroid at baseline, 22.2% had suboptimal thyroid control at 6 months.
• 41.7% had suboptimal thyroid control at 12 months.
• 59.6% had suboptimal thyroid control at 24 months.
• Kaplan-Meier analysis was used to compare thyroid function status across monitoring intervals.
• The proportion of euthyroid patients developing abnormal thyroid function approximately doubled with TFTs at 6, 12, and 24-month intervals.

The study was conducted in a primary care setting in Singapore using retrospective electronic health records from a group of polyclinics.

• Data were collected from July 2017 to June 2019 with a two-year follow-up period ending June 2020.
• Adults with a clinical diagnosis code for hypothyroidism in their electronic health records were included.
• The cohort had a mean age of 62.1 ± 13.29 years, was 79% female, and 79.7% Chinese.
• Stepwise logistic regression, Kaplan-Meier analysis, and appropriate statistical tests were used to analyze demographic, clinical, and TFT data.