Yu Oriana Hoi Yun, Filliter Christopher, Filion Kristian B, Platt Robert W, Grad Roland, Rad Mona Vahidi, Renoux Christel
Division of Endocrinology (Yu), Jewish General Hospital; Centre for Clinical Epidemiology (Yu, Filliter, Filion, Platt, Renoux), Lady Davis Institute, Jewish General Hospital; Departments of Epidemiology, Biostatistics and Occupational Health (Yu, Filion, Platt, Renoux), Medicine (Filion), Pediatrics (Platt), and Family Medicine (Grad), McGill University, Montréal, Que.; Division of Endocrinology (Vahidi Rad), Mayo Clinic, Scottsdale, Ariz.; Department of Neurology and Neurosurgery (Renoux), McGill University, Montréal, Que.
CMAJ. 2025 Jul 27;197(26):E744-E753. doi: 10.1503/cmaj.250356.
Subclinical hypothyroidism has been linked to adverse renal outcomes, but it is unknown whether treatment of subclinical hypothyroidism reduces the risk of these adverse outcomes. We sought to assess whether treatment of subclinical hypothyroidism with levothyroxine is associated with a decreased risk of developing adverse renal outcomes.
We conducted a population-based cohort study using a prevalent new-user design. Using the Clinical Practice Research Datalink in the United Kingdom, we assembled a study cohort of individuals aged 18 years and older with newly diagnosed subclinical hypothyroidism between 1998 and 2018. We matched individuals with subclinical hypothyroidism treated with levothyroxine to nontreated individuals with subclinical hypothyroidism based on age, sex, calendar time, duration of subclinical hypothyroidism, and time-conditional propensity score. We included several confounders, including data on demographics, clinical diagnoses, biochemical measures, lifestyle, and prescriptions, in the time-conditional propensity score estimate. The primary outcome was a composite end point of end-stage renal disease (requiring dialysis) and lowering of the estimated glomerular filtration rate of 50% or greater.
We matched 76 697 individuals with subclinical hypothyroidism treated with levothyroxine to 76 697 nontreated individuals. The mean age of the study cohort was 63 years, and 77% of patients were female. During a median follow-up time of 1.6 years (levothyroxine treated: 1.0, interquartile range [IQR] 0.4-2.7, yr; nontreated: 2.5, IQR 0.9-5.7, yr), 2426 adverse renal events occurred among nontreated individuals (incidence rate 8.35, 95% confidence interval [CI] 8.02-8.69, per 1000 person-years), and 1255 adverse renal events occurred among levothyroxine-treated individuals (incidence rate 7.93, 95% CI 7.50-8.39, per 1000 person-years). Treatment with levothyroxine was not associated with the risk of adverse renal outcomes among people with subclinical hypothyroidism (adjusted hazard ratio 0.97, 95% CI 0.90-1.04).
In this population-based cohort study, there was no evidence that levothyroxine treatment of subclinical hypothyroidism reduced the risk of adverse renal outcomes. Future studies in different populations and with longer duration of follow-up are needed to confirm these findings.
亚临床甲状腺功能减退与不良肾脏结局相关，但亚临床甲状腺功能减退的治疗是否能降低这些不良结局的风险尚不清楚。我们旨在评估左甲状腺素治疗亚临床甲状腺功能减退是否与不良肾脏结局发生风险降低相关。
我们采用现患新使用者设计进行了一项基于人群的队列研究。利用英国临床实践研究数据链，我们组建了一个研究队列，其中包括1998年至2018年间新诊断为亚临床甲状腺功能减退的18岁及以上个体。我们根据年龄、性别、日历时间、亚临床甲状腺功能减退持续时间和时间条件倾向评分，将接受左甲状腺素治疗的亚临床甲状腺功能减退个体与未治疗的亚临床甲状腺功能减退个体进行匹配。我们在时间条件倾向评分估计中纳入了几个混杂因素，包括人口统计学、临床诊断、生化指标、生活方式和处方数据。主要结局是终末期肾病（需要透析）和估计肾小球滤过率降低50%或更多的复合终点。
我们将76697例接受左甲状腺素治疗的亚临床甲状腺功能减退个体与76697例未治疗个体进行了匹配。研究队列的平均年龄为63岁，77%的患者为女性。在中位随访时间1.6年（左甲状腺素治疗组：1.0年，四分位间距[IQR]0.4 - 2.7年；未治疗组：2.5年，IQR 0.9 - 5.7年）期间，未治疗个体中发生了2426例不良肾脏事件（发病率8.35，95%置信区间[CI]8.02 - 8.69，每1000人年），左甲状腺素治疗个体中发生了1255例不良肾脏事件（发病率7.93，95% CI 7.50 - 8.39，每1000人年）。左甲状腺素治疗与亚临床甲状腺功能减退患者不良肾脏结局风险无关（调整后风险比0.97，95% CI 0.90 - 1.04）。
在这项基于人群的队列研究中，没有证据表明左甲状腺素治疗亚临床甲状腺功能减退可降低不良肾脏结局的风险。需要在不同人群中进行更长随访期的未来研究来证实这些发现。
