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[2型胺碘酮所致甲状腺毒症:发生率、发病时间及预测因素]

[Type 2 amiodarone-induced thyrotoxicosis: prevalence, time and predictors of development].

作者信息

Ermolaeva A S, Fadeev V V

机构信息

I.M. Sechenov First Moscow State Medical University (Sechenov University).

出版信息

Probl Endokrinol (Mosk). 2023 Oct 23;70(3):9-22. doi: 10.14341/probl13348.

Abstract

BACKGROUND

Amiodarone takes a leading position in arrhythmological practice in the prevention and relief of various cardiac arrhythmias. Type 2 amiodarone-induced thyrotoxicosis is a frequent side effect of the drug. It is the most complex type of thyroid dysfunction both in terms of the severity of clinical manifestations, and in terms of understanding the mechanisms of pathogenesis, possibility of differential diagnosis and providing effective treatment. Due to the increasing life expectancy of the population, corresponding increase in the frequency of cardiac arrhythmias, the problem does not lose its relevance. Identification of predictors, assessment and prediction of the individual risk of developing this thyroid pathology is a necessity in daily clinical practice for making a reasonable decision when prescribing the drug, determining the algorithm for further dynamic monitoring of the patient.

AIM

To evaluate the structure of amiodarone-induced thyroid dysfunction, prevalence, time and predictors of development type 2 amiodarone-induced thyrotoxicosis in a prospective cohort study. MATERIALS AND METHODS: The study involved 124 patients without thyroid dysfunction who received amiodarone therapy for the first time. Evaluation of the functional state of the thyroid gland was performed initially, after prescribing the drug for the first 3 months 1 time per month, in the future - every 3 months. The follow-up period averaged 12-24 months. The end of the observation occurred with the development of amiodaron-induced thyroid dysfunction or patient's refusal to further participate in the study. For the differential diagnosis of the type of amiodarone-induced thyrotoxicosis, the level of anti-TSH receptor antibodies and thyroid scintigraphy with technetium pertechnetate were determined. The type and frequency of thyroid dysfunction, time and predictors of development type 2 amiodarone-induced thyrotoxicosis were evaluated.

RESULTS

The structure of amiodarone-induced thyroid dysfunction was represented by hypothyroidism in 19,3% (n=24), type 1 thyrotoxicosis in 1,6% (n=2), type 2 thyrotoxicosis in 23,4% (n=29). The median time of its development was 92,0 [69,0;116,0] weeks; the average period of common survival - 150,2±12,6 weeks (95% CI: 125,5-175,0), median - 144±21,7 weeks (95% CI: 101,4-186,6). The main predictors of type 2 amiodarone-induced thyrotoxicosis were: age (OR=0,931; 95% CI: 0,895-0,968; p<0.001), BMI (OR=0,859; 95% CI: 0,762-0,967; p=0,012), time from the start of amiodarone therapy (OR=1,023; 95% CI: 1,008-1,038; p=0,003). Age ≤60 years was associated with increased risk of the dysfunction by 2.4 times (OR=2,352; 95% CI: 1,053-5,253; p=0,037), BMI≤26,6 kg/m2 - 2,3 times (OR=2,301; 95% CI: 1,025-5,165; p=0,043). CONCLUSION: The results allow to personalized estimate the risk of type 2 amiodarone-induced thyrotoxicosis and determine the patient's management tactic.

摘要

背景

胺碘酮在心律失常的预防和治疗中占据主导地位。胺碘酮诱发的2型甲状腺毒症是该药常见的副作用。无论是从临床表现的严重程度来看,还是从发病机制的理解、鉴别诊断的可能性以及提供有效治疗方面来看,它都是最复杂的甲状腺功能障碍类型。由于人口预期寿命的增加,心律失常的发病率相应上升,这个问题仍然具有现实意义。识别预测因素、评估和预测个体发生这种甲状腺病变的风险,对于在日常临床实践中合理用药、确定患者进一步动态监测的算法是必要的。

目的

在前瞻性队列研究中评估胺碘酮诱发的甲状腺功能障碍的结构、2型胺碘酮诱发的甲状腺毒症的发生率、发生时间及预测因素。

材料与方法

该研究纳入了124例首次接受胺碘酮治疗且无甲状腺功能障碍的患者。最初对甲状腺的功能状态进行评估,在开始用药后的前3个月每月评估1次,此后每3个月评估1次。随访期平均为12 - 24个月。观察结束于胺碘酮诱发的甲状腺功能障碍的发生或患者拒绝继续参与研究。为鉴别胺碘酮诱发的甲状腺毒症的类型,测定抗促甲状腺激素受体抗体水平并进行高锝酸盐甲状腺闪烁显像。评估甲状腺功能障碍的类型和发生率、2型胺碘酮诱发的甲状腺毒症的发生时间及预测因素。

结果

胺碘酮诱发的甲状腺功能障碍的结构表现为:甲状腺功能减退占19.3%(n = 24),1型甲状腺毒症占1.6%(n = 2),2型甲状腺毒症占23.4%(n = 29)。其发生的中位时间为92.0 [69.0;116.0]周;总生存平均时间为150.2±12.6周(95%可信区间:125.5 - 175.0),中位时间为144±21.7周(95%可信区间:101.4 - 186.6)。2型胺碘酮诱发的甲状腺毒症的主要预测因素为:年龄(比值比=0.931;95%可信区间:0.895 - 0.968;p<0.001)、体重指数(比值比=0.859;95%可信区间:0.762 - 0.967;p = 0.012)、胺碘酮治疗开始后的时间(比值比=1.023;95%可信区间:1.008 - 1.038;p = 0.003)。年龄≤60岁使功能障碍风险增加2.4倍(比值比=2.352;95%可信区间:1.053 - 5.253;p = 0.037),体重指数≤26.6kg/m²使风险增加2.3倍(比值比=2.301;95%可信区间:1.025 - 5.165;p = 0.043)。

结论

这些结果有助于个性化评估2型胺碘酮诱发的甲状腺毒症的风险,并确定患者的管理策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0941/11334237/4145b7985771/problendo-70-13348-g001.jpg

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