Lillevang-Johansen Mads, Abrahamsen Bo, Jørgensen Henrik Løvendahl, Brix Thomas Heiberg, Hegedüs Laszlo
Department of Endocrinology and Metabolism, Odense University Hospital, 5000 Odense, Denmark.
Institute of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark.
J Clin Endocrinol Metab. 2017 Jul 1;102(7):2301-2309. doi: 10.1210/jc.2017-00166.
Cumulative time-dependent excess mortality in hyperthyroid patients has been suggested. However, the effect of antithyroid treatment on mortality, especially in subclinical hyperthyroidism, remains unclarified. We investigated the association between hyperthyroidism and mortality in both treated and untreated hyperthyroid individuals.
Register-based cohort study of 235,547 individuals who had at least one serum thyroid-stimulating hormone (TSH) measurement in the period 1995 to 2011 (7.3 years median follow-up). Hyperthyroidism was defined as at least two measurements of low serum TSH. Mortality rates for treated and untreated hyperthyroid subjects compared with euthyroid controls were calculated using multivariate Cox regression analyses, controlling for age, sex, and comorbidities. Cumulative periods of decreased serum TSH were analyzed as a time-dependent covariate.
Hazard ratio (HR) for mortality was increased in untreated [1.23; 95% confidence interval (CI), 1.12 to 1.37; P < 0.001], but not in treated, hyperthyroid patients. When including cumulative periods of TSH in the Cox regression analyses, HR for mortality per every 6 months of decreased TSH was 1.11 (95% CI, 1.09 to 1.13; P < 0.0001) in untreated hyperthyroid patients (n = 1137) and 1.13 (95% CI, 1.11 to 1.15; P < 0.0001) in treated patients (n = 1656). This corresponds to a 184% and 239% increase in mortality after 5 years of decreased TSH in untreated and treated hyperthyroidism, respectively.
Mortality is increased in hyperthyroidism. Cumulative periods of decreased TSH increased mortality in both treated and untreated hyperthyroidism, implying that excess mortality may not be driven by lack of therapy, but rather inability to keep patients euthyroid. Meticulous follow-up during treatment to maintain biochemical euthyroidism may be warranted.
已有研究提示甲状腺功能亢进症（甲亢）患者存在累积时间依赖性的额外死亡率。然而，抗甲状腺治疗对死亡率的影响，尤其是在亚临床甲亢患者中，仍不明确。我们调查了已治疗和未治疗的甲亢个体中甲亢与死亡率之间的关联。
基于登记的队列研究，纳入了235,547名在1995年至2011年期间至少进行过一次血清促甲状腺激素（TSH）测量的个体（中位随访时间7.3年）。甲亢定义为至少两次测量血清TSH降低。使用多变量Cox回归分析计算已治疗和未治疗的甲亢受试者与甲状腺功能正常对照者的死亡率，并对年龄、性别和合并症进行校正。将血清TSH降低的累积时间段作为时间依赖性协变量进行分析。
未治疗的甲亢患者死亡率的风险比（HR）升高[1.23；95%置信区间（CI），1.12至1.37；P<0.001]，而治疗后的甲亢患者死亡率的HR未升高。在Cox回归分析中纳入TSH的累积时间段后，未治疗的甲亢患者（n = 1137）中每降低6个月TSH的死亡率HR为1.11（95%CI，1.09至1.13；P<0.0001），治疗后的患者（n = 1656）中为1.13（95%CI，1.11至1.15；P<0.0001）。这分别对应未治疗和治疗的甲亢患者TSH降低5年后死亡率增加184%和239%。
甲亢患者死亡率升高。TSH降低的累积时间段在已治疗和未治疗的甲亢患者中均增加死亡率，这意味着额外死亡率可能不是由缺乏治疗导致，而是无法使患者维持甲状腺功能正常。治疗期间进行细致的随访以维持生化甲状腺功能正常可能是必要的。
