臺灣博碩士論文加值系統

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.

口試委員會審定書 I
致謝………………………………………………………………………..II
中文摘要 III
英文摘要 IV
第一章 研究背景與動機 1
第一節 先天性甲狀腺低能症 1
第二節 先天性甲狀腺低能症新生兒篩檢 4
第三節 先天性甲狀腺低能症新生兒篩檢方法比較 6
第四節 先天性甲狀腺低能症新生兒篩檢方式改良 9
第二章 研究方法 11
第一節 實驗方法 11
第二節 研究對象 12
第三節 實驗原理 12
第四節 統計分析方法 14
第三章 實驗結果 15
第一節 檢體 15
第二節 T4檢測結果 16
第三節 使用T4檢驗協助判斷陽性個案 17
第四節 應用T4進階篩檢對篩檢結果的影響 18
第五節 TSH與T4數值間的關係 19
第六節 影響TSH與T4數值的因子 22
第四章 討論 25
第一節 臨界值的選擇 25
第二節 T4數值在TSH上升者的分布 26
第三節 其它篩檢方法 27
第四節 先天性甲狀腺低能症新生兒篩檢之諮詢、偽陽性對家長的影響 27
第五節 改良後方法之優缺點 28
第六節 改良後方法之建議流程 29
第五章 參考文獻 31

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