Department of Internal Medicine and Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
PLoS Med. 2019 Oct 25;16(10):e1002957. doi: 10.1371/journal.pmed.1002957. eCollection 2019 Oct.
Variations in thyroid function within reference ranges are associated with increased risk of diseases and death. However, the impact of thyroid function on life expectancy (LE) with and without noncommunicable diseases (NCDs) remains unknown. We therefore aimed to investigate the association of thyroid function with total LE and LE with and without NCD among euthyroid individuals.
The study was embedded in the Rotterdam Study, a prospective population-based study carried out in the Netherlands. In total, 7,644 participants without known thyroid disease and with thyroid-stimulating hormone (TSH) and free thyroxine (FT4) levels within reference ranges were eligible. NCDs were defined as presence of cardiovascular disease, diabetes mellitus type 2, or cancer. We used the demographic tool of multistate life tables to calculate LE estimates at the age of 50 years, using prevalence, incidence rates, and hazard ratios for three transitions (healthy to NCD, healthy to death, and NCD to death). The total LE and LE with and without NCD among TSH and FT4 tertiles were calculated separately in men and women. Analyses were adjusted for sociodemographic and cardiovascular risk factors. The mean (standard deviation) age of the participants was 64.5 (9.7) years, and 52.3% were women. Over a median follow-up of 8 years (interquartile range 2.7-9.9 years), 1,396 incident NCD events and 1,422 deaths occurred. Compared with those in the lowest TSH tertile, men and women in the highest TSH tertile were expected to live 1.5 years (95% confidence interval [CI] 0.8-2.3, p < 0.001) and 1.5 years (CI 0.8-2.2, p < 0.001) longer, respectively, of which 1.4 years (CI 0.5-2.3, p = 0.002) and 1.3 years (CI 0.3-2.1, p = 0.004) with NCD. Compared with those in the lowest FT4 tertile, the difference in LE for men and women in the highest FT4 tertile was -3.7 years (CI -5.1 to -2.2, p < 0.001) and -3.3 years (CI -4.7 to -1.9, p < 0.001), respectively, of which -1.8 years (CI -3.1 to -0.7, p = 0.003) and -2.0 years (CI -3.4 to -0.7, p = 0.003) without NCD. A limitation of the study is the observational design. Thus, the possibility of residual confounding cannot be entirely ruled out.
In this study, we found that people with low-normal thyroid function (i.e., highest tertile of TSH and lowest tertile of FT4 reference ranges) are expected to live more years with and without NCD than those with high-normal thyroid function (i.e., lowest tertile of TSH and highest tertile of FT4 reference ranges). These findings provide support for a re-evaluation of the current reference ranges of thyroid function.
参考范围内甲状腺功能的变化与疾病和死亡风险的增加有关。然而，甲状腺功能对无慢性病（NCD）的预期寿命（LE）和有 NCD 的 LE 的影响仍不清楚。因此，我们旨在调查甲状腺功能与甲状腺功能正常个体的总 LE 以及有无 NCD 的 LE 之间的关系。
该研究嵌入在鹿特丹研究中，这是一项在荷兰进行的前瞻性人群为基础的研究。共有 7644 名无已知甲状腺疾病且促甲状腺激素（TSH）和游离甲状腺素（FT4）水平在参考范围内的参与者符合条件。NCD 定义为存在心血管疾病、2 型糖尿病或癌症。我们使用多状态生命表的人口统计学工具来计算 50 岁时的 LE 估计值，使用三种过渡（健康到 NCD、健康到死亡和 NCD 到死亡）的患病率、发病率和危险比。分别在男性和女性中计算 TSH 和 FT4 三分位数的总 LE 和无 NCD 的 LE。分析调整了社会人口统计学和心血管危险因素。参与者的平均（标准差）年龄为 64.5（9.7）岁，52.3%为女性。在中位随访 8 年（四分位距 2.7-9.9 年）期间，发生了 1396 例新的 NCD 事件和 1422 例死亡。与 TSH 最低三分位组相比，TSH 最高三分位组的男性和女性预期寿命分别延长 1.5 年（95%置信区间 [CI] 0.8-2.3，p < 0.001）和 1.5 年（CI 0.8-2.2，p < 0.001），其中 1.4 年（CI 0.5-2.3，p = 0.002）和 1.3 年（CI 0.3-2.1，p = 0.004）有 NCD。与 FT4 最低三分位组相比，FT4 最高三分位组的男性和女性的 LE 差异分别为-3.7 年（CI-5.1 至-2.2，p < 0.001）和-3.3 年（CI-4.7 至-1.9，p < 0.001），其中-1.8 年（CI-3.1 至-0.7，p = 0.003）和-2.0 年（CI-3.4 至-0.7，p = 0.003）无 NCD。该研究的一个局限性是观察性设计。因此，不能完全排除残留混杂的可能性。
在这项研究中，我们发现甲状腺功能正常的低正常值（即 TSH 最高三分位和 FT4 参考范围最低三分位）的人比甲状腺功能正常的高正常值（即 TSH 最低三分位和 FT4 参考范围最高三分位）的人预期有更多的年数与无 NCD。这些发现为重新评估当前的甲状腺功能参考范围提供了支持。
