改良臺灣先天性甲狀腺低能症之新生兒篩檢方法

Abstract

背景：患有先天性甲狀腺低能症的病童，在發育的過程，會因為缺乏甲狀腺素(Thyroxine; T4)，造成嚴重的代謝生長遲緩，和腦部發育受損而產生智能障礙，但目前已經由新生兒篩檢，及早發現並給予甲狀腺素(Levothyroxine) 補充而防止。然現行篩檢偽陽性率約為2-3%，部份患者需經過數次篩檢後，才會轉介至確認診斷系統加以確認並開始給與治療。 方法：測定甲促素（Thyroid stimulating hormone, TSH）初檢值為9 ~ 40 μU/mL者，加驗同血片之甲狀腺素(T4)作為進階篩檢標誌物，探討合併判讀TSH和T4是否可以降低初次篩檢的複檢率。 結果：先天性甲狀腺低能症新生兒篩檢在本試驗階段其間之複檢率為2.35%，本試驗共測定初檢TSH介於9 ~ 40 μU/mL且需複檢之個案共900名，其甲促素(TSH)和甲狀腺素(T4)兩者確有負相關（相關係數-0.21）。若使用T4作為進階篩檢標誌物，以9.79 μg/dL作為臨界值，則敏感度為72.9%、特異度73.7%、偽陰性26.3%，偽陽性27.1%。加做T4檢驗後，在TSH初檢有輕微異常的新生兒而需要複檢的900名個案中，有627名個案不需再次複檢TSH就可判定為陰性結果，但有13名陽性個案會因為T4未降低而可能成為偽陰性。 結論：使用甲狀腺素作為進階篩檢之標誌物，雖然可以降低複檢率，減少新生兒複檢次數，然而部份陽性個案未達T4缺乏的標準，因此可能造成偽陰性。如何進一步改進篩檢方式以增進篩檢效能仍待進一步研究。

Background: Children with congenital hypothyroidism will have severe growth retardation, impaired brain development and mental retardation due to lack of thyroxine. These symptoms are preventable via early detection by newborn screening and supplement of Levothyroxine. However, currently the screening false positive rate is about 2-3%, and therefore the diagnosis most patients require re-screening before referral to the diagnosis system to confirm hypothyroidism and begin treatments. Method: To explore the possibility to decrease the false-positive rate of screening. Dry blood spot thyroxine (T4) level was used as a second tier marker for newborns with a positive first screening result of congenital hypothyroidism (thyroid stimulating hormone (TSH) levels between 9 and 40 μU/mL). Result: The positive rate of first screening was 2.35% during the study period. There were 900 cases whose TSH levels were 9 to 40 μU/mL and needed a retest. Their TSH and T4 levels have negative correlation (correlation coefficient: -0.21). If we add thyroxine as a second tier screening marker and use 9.79 μg/dL as thyroxine cut-off, the sensitivity of screening is 72.9%, specificity 73.7%, false-negative rate 26.3%, and false positive rate 27.1%. After adding thyroxine test, 627 false-positive cases can be classify as negative result with no need of retest, but 13 positive cases will be missed due to a normal thyroxine level. Conclusion: Althought using thyroxine as a second tier marker can reduce the recall rate of newborn screening, but the false-negative rate also increase. Therefore, further studies will be required to improve the screening of congenital hypothyroidism.