新生兒期高促甲狀腺素血症患童接受促甲狀腺素釋放激素測試及單獨使用促甲狀腺素評估甲狀腺功能之比較

背景：促甲狀腺素釋放激素測試(TRH test)除了可以鑑別甲狀腺低能症的原因是原發性或次發性之外，還可以診斷出比次臨床甲狀腺低能症(subclinical hypothyroidism)更早期的次生化甲狀腺低能症(sub-biochemical hypothyroidism)，以往的證據均建議將促甲狀腺素釋放激素測試的閾值訂為10~ 40 mIU/L。然而，有些學者認為，目前臨床上廣為使用的新一代的促甲狀腺素(TSH)測驗方法有極佳的靈敏度，在診斷甲狀腺低能症方面可以完全取代。本研究目的即是探討在診斷甲狀腺低能症方面，促甲狀腺釋放激素測試是否優於單獨使用促甲狀腺素測驗。方法：本研究為一回溯性研究。我們總共收集了在1989至2008年間共228位在新生兒時期有正常甲狀腺發育但有高促甲狀腺素血症表現並接受甲狀腺素補充的病童，於三歲的停藥評估時，利用促甲狀腺素釋放激素測試前的促甲狀腺素基礎值與促甲狀腺素釋放激素測驗後的促甲狀腺素高峰值作統計分析，評估病童停藥後是否出現甲狀腺低能症。評估後不論是否停藥均持續追蹤至少一年以上以確定病童後續是否有發展出臨床的甲狀腺低能或是否有過度治療的情形。結果：對於有正常甲狀腺發育但有新生兒高促甲狀腺素血症的病童， 31.6%的病童會持續有甲狀腺低能的情形。以ROC曲線(receiver operating characteristic curve)來看，在多數情況下，單獨使用促甲狀腺素基礎值和接受促甲狀腺素釋放激素測驗後的促甲狀腺素高峰值都能正確診斷次臨床甲狀腺低能症；促甲狀腺素基礎值對於正常甲狀腺功能的預測其特異性可達100%，但敏感性只有40.4%。若促甲狀腺素基礎值超過正常值範圍，接近正常值上限時(4.5~8.5 mIU/L)，促甲狀腺素釋放激素測驗後的促甲狀腺素高峰值有較好的鑑別力(p = 0.033)。同時，促甲狀腺素高峰值的閾值訂在60 mIU/L可以有較好的敏感性及特異性。結論：新生兒高促甲狀腺素血症是日後持續出現甲狀腺低能症的危險因子。單獨使用促甲狀腺素的基礎值與促甲狀腺素釋放激素測試後的促甲狀腺素高峰值均可用於診斷甲狀腺低能症。但若促甲狀腺素基礎值接近於正常值上限時，促甲狀腺素釋放激素測試有較高的鑑別力。我們建議促甲狀腺素釋放激素測試的閾值訂於60 mIU/L；當病童的測試高峰值高於60 mIU/L時，可診斷為甲狀腺低能症，建議應施予甲狀腺素補充。

關鍵字

促甲狀腺素釋放激素測試；先天性甲狀腺低能症；新生兒高促甲狀腺素血症

並列摘要

Background: Thyrotropin-releasing hormone (TRH) test is useful for differentiating central and primary hypothyroidism, and is also valuable for diagnosing sub-biochemical hypothyroidism, an earlier stage than subclinical hypothyroidism, and usually the threshold of TRH test was set at 10~40 mIU/L. However, some experts are of the opinion that TRH test has a limited role in evaluating the early stage of hypothyroidism after the new generation of the thyroid-stimulating hormone (TSH) assay was applied to clinical use. The aim of this study was to investigate whether TRH test detects subclinical hypothyroidism earlier than TSH assay alone. Methods: This is a retrospective case analysis. Totally 228 children with thyroid eutopia who had neonatal hyperthyrotropinemia (HT) under levothyroxine supplement were collected between 1989 and 2008. Basal TSH level and TRH test were performed at the age of three to evaluate whether hypothyroidism developed after levothyroxine discontinued, and statistic analysis was performed. All the patients received follow-up visits for cognitive development and thyroid function after the TRH test to avoid over- or under-treatment. Results: In patients with thyroid eutopia and neonatal HT, 31.6% of them were still in status of hypothyroidism after the age of three if without supplement of levothyroxine. The basal TSH has good specificity (100%) for diagnosing euthyroidism, but with only 40.38% of sensitivity. When the basal TSH level was near the upper limit of normal range (4.5~8.5 mIU/L), the TRH test result correlated with hypothyroidism better (p = 0.033). The threshold of the TRH test set at 60 mIU/L had greater area under the curve compared with the previous threshold. Conclusions: Neonatal HT is a risk factor of hypothyroidism. We suggest the TRH test be administered in children with a basal TSH value near the upper limit of the normal range; the threshold of the TRH test may be set at 60 mIU/L. When the peak TSH level is above 60 mIU/L, the child is in hypothyroidism and usually needs levothyroxine supplement.

並列關鍵字

TRH test ； congenital hypothyroidism ； neonatal hyperthyrotropinemia

參考文獻

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新生兒期高促甲狀腺素血症患童接受促甲狀腺素釋放激素測試及單獨使用促甲狀腺素評估甲狀腺功能之比較

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