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Low T3 syndrome in Kawasaki disease: Relation to serum levels of tumor necrosis factor-α, interleukin-6 and NT-proBNP

가와사끼병에서의 저 T3 증후군 : 혈청 tumor necrosis factor-α, interleukin-6 및 NT-proBNP 농도와의 관계

  • Cho, Hye Kyung (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Sohn, Jin A (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Kim, Hae Soon (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Sohn, Sejung (Department of Pediatrics, Ewha Womans University School of Medicine)
  • 조혜경 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 손진아 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 김혜순 (이화여자대학교 의학전문대학원 소아과학교실) ;
  • 손세정 (이화여자대학교 의학전문대학원 소아과학교실)
  • Received : 2008.09.15
  • Accepted : 2008.11.03
  • Published : 2009.02.15

Abstract

Purpose : We investigated the relationship between thyroid hormone and serum tumor necrosis factor (TNF-${\alpha}$), interleukin (IL-6) and N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in patients with Kawasaki disease (KD). Methods : Serum levels of thyroid hormone, TNF-${\alpha}$, IL-6, and NT-proBNP were measured in 52 KD patients in the acute and subacute phase and 10 patients with acute febrile illness (control group). TNF-${\alpha}$ and IL-6 were determined by sandwich enzyme-linked immunosorbent assay (ELISA). Echocardiography was performed to detect coronary artery lesions (CAL) in KD patients. Results : Low $T_3$ syndrome occurred in 63.5% of KD patients. $T_3$ in the acute phase of KD was lower than that in the control. In KD patients, $T_3$ was lowered in the acute phase and elevated in the subacute phase, whereas TNF-${\alpha}$, IL-6 and NT-proBNP were elevated in the acute phase and decreased in the subacute phase. NT-proBNP, and IL-6 were higher in patients with low $T_3$ than in those with normal $T_3$. In addition, $T_3$ inversely correlated with IL-6 and NT-proBNP. Of the 4 patients with CAL, 3 had very low $T_3$. Compared with intravenous immunoglobulin (IVIG)-responsive patients, IVIG-resistant patients had lower $T_3$ and higher IL-6 and NT-proBNP. Conclusion : $T_3$ decreases in the acute phase of KD and normalizes in the subacute phase without thyroid hormone replacement. Low $T_3$ may be partially induced by IL-6 rather than TNF-${\alpha}$, and is strongly associated with high NT-proBNP. $T_3$ in KD may be used for the differential diagnosis, monitoring the activity of the disease, and predicting the severity of inflammation.

목 적 : 가와사끼병에서 갑상샘 호르몬과 혈청 TNF-${\alpha}$, IL-6 및 NT-proBNP 농도와의 연관성을 알아보고자 하였다. 방 법 : 환자군으로 가와사끼병 환아 52명과 대조군으로 다른 열성 질환 환아 10명을 대상으로 하였다. 환자군의 치료 전 급성기와 치료 3-9일 후의 아급성기 때의 혈청과 대조군의 급성 발열기 혈청에서 갑상샘 호르몬과 TNF-${\alpha}$, IL-6, NT-proBNP를 각각 측정하여 비교하였다. 환자군에서는 심장 초음파검사로 관상동맥 병변의 유무를 조사하였다. 결 과 : 가와사끼병의 63.5%에서 저 $T_3$ 증후군($T_3$<100 ng/dL)이 동반되었다. 급성 가와사끼병의 $T_3$는 대조군에 비해 유의하게 낮았다($86.8{\pm}36.6$ vs $116.7{\pm}24.4$ ng/dL, P<0.05). 가와사끼병 환자군에서 $T_3$는 급성기에 감소하고 갑상샘 호르몬의 치료없이 아급성기에 증가하였으나($84.3{\pm}33.0$ vs $109.3{\pm}37.5$ ng/dL, P<0.01), 반대로 TNF-${\alpha}$, IL-6 및 NT-proBNP는 모두 급성기에 증가하고 아급성기에 감소하였다. 가와사끼병 환자군에서 저 $T_3$군(n=33)은 정상 $T_3$군(n=19)에 비해 신장 및 간기능의 차이는 없었고, NT-proBNP는 높았으며, IL-6는 약간 높은 경향을 보였다. 또한 $T_3$는 IL-6 (r=-0.12, P>0.05) 및 NT-proBNP(r=-0.54, P<0.001)와 반비례 관계를 보였다. 관상동맥 병변을 보인 가와사끼병 환아 4명 중 3명에서 $T_3$가 25.0-42.7 ng/dL로 매우 감소하였다. 면역글로불린 치료반응군(n=45)에 비해 저항군(n=7)에서 $T_3$는 더 낮았고($93.8{\pm}33.5$ vs $41.6{\pm}19.8$ ng/dL, P<0.001), IL-6와 NT-proBNP는 더 높았다. 결 론 : $T_3$는 가와사끼병의 급성기에 감소되며 아급성기에 갑상샘 호르몬의 치료 없이 정상화된다. $T_3$ 감소는 부분적으로 TNF-${\alpha}$ 보다는 IL-6의 작용에 의해 유발되며 NT-proBNP의 상승과 연관된다. 가와사끼병에서 $T_3$ 측정은 다른 열성 질환과의 감별진단에, 질병경과를 모니터하는데, 심근 손상의 초기 표식자로, 질병의 심한 정도를 예측하는데 이용할 수 있으리라 생각된다.

Keywords

Acknowledgement

Supported by : Ewha Womans University Mokdong Hospital

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