High Incidence of Treatment-Related Hypothyroidism in Multidrug-Resistant Tuberculosis Patients
黃萬均(Wan-Chun Huang)；黃晟維(Cheng-Wei Huang)；徐克明(Ko-Ming Hsu)；簡慎萱(Shen-Hsuan Chien)；余明治(Ming-Chih Yu)
多重抗藥性結核 ； 甲狀腺功能低下症 ； 丙硫異煙胺 ； 對氨基水楊酸 ； multidrug-resistant tuberculosis ； hypothyroidism ； prothionamide ； p-aminosalicylic acid
|Volume or Term/Year and Month of Publication||
29卷4期（2014 / 08 / 01）
209 - 217
背景：甲狀腺功能低下症是已知的多重抗藥性結核治療副作用，在過去被認為是罕見的狀況，然而最近文獻報導的發生率介於3.5到71.4%。甲狀腺功能低下症的發生被認為和丙硫異煙胺、乙硫磷酰胺及對氨基水楊酸有關，但合併這些藥物的使用是否影響甲狀腺功能低下症的發生並不清楚。本研究回顧性分析多重抗藥性結核病人產生甲狀腺功能低下症的機率以及與這些藥物的相關性。方法：本研究回顧性分析從2009年1月1日至2012年3月31日開始接受治療的50位多重抗藥性結核病人，並且這些病人都追蹤至治療完成或至少到2013年3月31日。我們收集病人的臨床特徵、共病、基礎血液檢測及甲狀腺功能、丙硫異煙胺和對氨基水楊酸的使用以及促甲狀腺激素數值進行分析。結果：50位病人中有24位（48%）發生甲狀腺功能低下症，從治療開始到檢測出甲狀腺功能低下症的中位時間及平均時間分別為151天及162天，發生甲狀腺功能低下症的病人比起沒有發生的病人明顯較年輕（p=0.045）。丙硫異煙胺及對氨基水楊酸和甲狀腺功能低下症的發生有關聯性，這兩種藥物合併使用比單純使用丙硫異煙胺有更高的發生率（odds ratio=4.385, p=0.03）。結論：甲狀腺功能低下症在接受多重抗藥性結核治療的病人中是常見的，在合併使用丙硫異煙胺和對氨基水楊酸的病人中其發生率更高。臨床人員應該留意這個可能的副作用，並且觀察相關的臨床症狀，特別是較年輕的病人及開始治療的前幾個月。我們認為，開始治療後一個月即進行促甲狀腺素的測量可能是必要的。
Background: Hypothyroidism is a known adverse effect of treatment for multidrug-resistant tuberculosis (MDR-TB). It has been suspected to be rare; however, recent studies report an incidence ranging from 3.5% to 71.4%. Development of hypothyroidism is considered to be attributed to the administration of prothionamide, ethionamide, and p-aminosalicylic acid, but whether a combination of these drugs influences this development is not known. The present study retrospectively analyzed the incidence of hypothyroidism in patients treated for MDR-TB and the correlation with these drugs. Methods: The records of 50 patients treated for MDR-TB from January 1, 2009 to March 31, 2012 were retrospectively analyzed. All patients were followed until completion of treatment, or until March 31, 2012. Data regarding patient characteristics, co-morbidities, baseline blood test and thyroid function test results, administration of prothionamide and p-aminosalicylic acid, and thyroid-stimulation hormone (TSH) levels during treatment were extracted for analysis. Results: Twenty-four (48%) of the 50 patients developed hypothyroidism. The median and mean times from start of treatment to detection of hypothyroidism were 151 days and 162 days, respectively. Patients who developed hypothyroidism were significantly younger (p=0.045) than those who did not. Prothionamide and p-aminosalicylic acid were found to be associated with hypothyroidism development. The combination of these 2 drugs was associated with a higher risk of developing hypothyroidism (odds ratio=4.385, p=0.03) than the use of prothionamide alone. Conclusion: Hypothyroidism is relatively common in patients treated for MDR-TB. The incidence is higher in patients receiving a combination of prothionamide and p-aminosalicylic acid. Clinicians should be aware of this possible adverse effect, and watch for clinical symptoms and signs suggesting hypothyroidism, especially in young patients and during the first few months of treatment. Beginning TSH testing as early as 1 month after beginning treatment may be appropriate.