抗甲状腺药物致血清肌酸激酶升高/横纹肌溶解症的循证分析

    Evidence Based Analysis of Anti-thyroid Drug-Induced Serum Creatine Kinase Elevation/Rhabdomyolysis

    • 摘要:
      目的  分析抗甲状腺药物(anti-thyroid drug,ATD)致血清肌酸激酶(creatine kinase,CK)升高伴肌痛、横纹肌溶解症的临床特点,为临床诊治提供证据和参考。
      方法 计算机检索CNKI、WanFang、VIP、CBM、PubMed和Embase数据库,截止时间为2024年4月,纳入ATD致CK升高伴肌痛或横纹肌溶解症的中英文文献。
      结果 共检索文献1751篇,最终纳入39篇共52例药物不良反应(adverse drug reactions,ADR),50例血清CK升高,49例主诉肌痛;7例进展为横纹肌溶解症,其中1例并发急性肾损伤。涉及52例患者,多为亚洲人群(占80.8%),女性占73.1%,中位年龄为26.0岁(20.0~33.8岁),<18岁儿童占17.3%。发生时间为ATD治疗后7~122 d,中位时间为30 d(26.3~56.3 d);处置措施包括ATD减量、停药、换药,加用左甲状腺素等;肌痛症状消失时间为1~122 d,中位时间为12 d(2.5~21.0 d);血清CK水平恢复正常的中位时间为24.5 d(14.0~43.8 d)。10例患者在后续治疗中再次出现血清CK升高伴肌痛。
      结论 ATD相关的血清CK升高伴肌痛是一种新的、鲜少被关注的ADR,医务人员应加强认识、及早诊治,避免进展为横纹肌溶解症、急性肾损伤等。ATD存在剂量依赖性,且亚洲人群可能更易感,在ATD初始治疗或增加剂量后2个月内,建议每月随访血清CK水平,尤其是主诉肌肉痉挛、肌痛的患者。

       

      Abstract:
      OBJECTIVE To analyse the clinical characteristics of serum creatine kinase (CK) elevation with myalgia and rhabdomyolysis induced by anti-thyroid drug (ATD), and to provide evidence and reference for clinical practice.
      METHODS A computerised search of CNKI, Wanfang, VIP, CBM, PubMed and Embase databases was conducted with a cut-off date of April 2024 to include Chinese and English literature on CK elevation with myalgia or rhabdomyolysis induced by ATD.
      RESULTS A total of 1751 literature articles were searched, and 39 articles with a total of 52 adverse drug reactions(ADRs) were finally included, with 50 cases of elevated serum CK and 49 cases complaining of myalgia; 7 cases progressed to rhabdomyolysis, including 1 case with concomitant acute kidney injury. Fifty-two patients were involved, mostly from Asian populations (80.8%), 73.1% female, with a median age of 26.0 years (20.0−33.8 years) and 17.3% children under 18 years of age. The time of onset ranged from 7 to 122 d after treatment with ATD, with a median of 30 d (26.3−56.3 d); dispositions included ATD dose reduction, discontinuation, substitution with other ATD, or addition of levothyroxine; myalgia symptoms resolved within 1 to 122 d, with a median of 12 d (2.5−21.0 d); and the median time to return to normal serum CK levels was 24.5 d (14.0−43.8 d). Ten patients had a recurrence of elevated serum CK with myalgia during subsequent treatment.
      CONCLUSION to ATD-induced elevated serum CK with myalgia is a new and under-recognised ADR that healthcare professionals should be more aware of and diagnose and treat early to prevent progression to rhabdomyolysis and acute kidney injury, etc. It is dose-dependent and may be more susceptible in Asian populations. Monthly monitoring of serum CK levels is recommended within 2 months of initial treatment or dose increase of ATD, especially in patients complaining of muscle cramps and myalgia.

       

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