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

Abstract

BackgroundLong-term management of patients with hypothyroidism on thyroxine replacement requires thyroid function test (TFT) monitoring once every six–12 months as recommended by clinical practice guidelines. This study determined their thyroid function status during two-year follow-up visits in primary care, and the factors influencing their thyroid status, and assessed the optimal interval for TFTs.MethodsA retrospective cohort study was conducted on adults with a clinical diagnosis code for hypothyroidism in their electronic health records taken from a group of polyclinics in Singapore between July 2017 and June 2020. The follow-up thyroid status was categorized as under-replacement (TSH ≥ 3.70mIU/L), over-replacement (TSH ≤ 0.65mIU/L) or euthyroid (TSH 0.65–3.70mIU/L). The patients’ demographic, clinical and TFT data were analyzed using appropriate statistical tests during the two-year follow-up. Stepwise logistic regression analysis identified the factors associated with suboptimal thyroid control. Kaplan–Meier analysis was used to compare their thyroid function status in association with the interval between TFT monitoring.ResultsData from 5,749 eligible subjects (mean age 62.1 ± 13.29 years; 79% female; 79.7% Chinese) were analyzed. After a two-year follow-up, 61.9% (n = 3558) of all subjects were euthyroid, with 29.5% (n = 1694) being under-replaced and 8.6% (n = 497) over-replaced. However, thyroid status did not differ significantly with the various dose regimen (daily, segmented, or alternate days) (p = 0.193). Stepwise logistic regression showed that thyroxine under-replacement was significantly associated with the male gender (AOR = 1.25,95%CI = 1.03–1.51,p = 0.02) and obesity (AOR = 1.34,95%CI = 1.08–1.66,p = 0.008). Every unit (μg/kg body weight) increase in the mean daily thyroxine dose was associated with 2.72 times greater odds of over-replacement. When comparing thyroid function monitoring at intervals of 13-24 months, monitoring at shorter intervals (≤ 12 months) was less likely to detect thyroxine under-replacement (AOR = 0.57,95%CI = 0.44–0.74,p < 0.001) and over-replacement (AOR = 0.62,95%CI = 0.41–0.97,p = 0.033). Among the 3,312 adults who were euthyroid at baseline, 22.2%, 41.7% and 59.6% had suboptimal thyroid control at 6, 12 and 24 months respectively (Kaplan–Meier analysis).ConclusionAround six in ten patients were euthyroid with thyroxine replacement for hypothyroidism in primary care over two years. Thyroxine under-replacement was associated with male gender and obesity. The proportion of euthyroid patients developing abnormal thyroid function doubled with TFTs at six, 12 and 24-month intervals.