




[摘要] 目的 探討甲狀腺功能與注意缺陷多動(dòng)障礙(attention deficit hyperactivity disorder,ADHD)兒童多動(dòng)行為(hyperactivity behavior,HB)之間的關(guān)系,進(jìn)一步了解導(dǎo)致ADHD風(fēng)險(xiǎn)增加的潛在因素,為兒童ADHD的治療提供參考。方法 選取2018年2月至2023年8月于湖州市中心醫(yī)院治療并隨訪的134例ADHD患兒作為研究對(duì)象,根據(jù)多動(dòng)指數(shù)(hyperactivity index,HI)分為非HB組(n=71)和HB組(n=63),比較兩組患兒的一般資料和常規(guī)實(shí)驗(yàn)室參數(shù),通過(guò)二分類(lèi)Logistic回歸分析評(píng)估HB相關(guān)因素,通過(guò)Pearson直線相關(guān)分析和受試者操作特征曲線探討HB與血清促甲狀腺激素(thyroid stimulating hormone,TSH)的關(guān)系及TSH水平在區(qū)分ADHD兒童HB方面的潛在診斷價(jià)值。結(jié)果 HB組患兒的乳酸、TSH水平高于非HB組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.05);TSH水平與HB獨(dú)立相關(guān),與HI得分呈正相關(guān)(r=0.668,Plt;0.001);TSH水平在區(qū)分ADHD兒童HB方面具有一定的價(jià)值,截?cái)嘀禐?.57μIU/ml(敏感度65.1%,特異性74.7%)。結(jié)論 本研究揭示血清TSH水平與ADHD患兒的HB呈正相關(guān),可用于區(qū)分ADHD兒童的HB。
[關(guān)鍵詞] 注意缺陷多動(dòng)障礙;多動(dòng)指數(shù);促甲狀腺激素
[中圖分類(lèi)號(hào)] R729" """"[文獻(xiàn)標(biāo)識(shí)碼] A""" [DOI] 10.3969/j.issn.1673-9701.2025.03.004
[Abstract] Objective To explore the relationship between thyroid function and hyperactivity behavior (HB) in children with attention deficit hyperactivity disorder (ADHD), and further understand the potential factors contributing to increased risk of ADHD, and provide references for the treatment of ADHD in children. Methods A total of 134 pediatric ADHD patients who were treated and followed up at Huzhou Central Hospital from February 2018 to August 2023 were selected as the research subjects. According to the hyperactivity index (HI), they were divided into non HB group (n=71) and HB group (n=63). General information and routine laboratory parameters were compared between two groups. HB-related factors were evaluated by using binary Logistic regression analysis. Finally, Pearson linear correlation analysis and receiver operating characteristic curve were used to study the relationship between HB and thyroid stimulating hormone (TSH) and the potential diagnostic value of TSH levels in distinguishing ADHD children with HB. Results The differences in lactic acid and TSH levels between two groups of cases were statistically significant, with HB group significantly higher compared to non HB group (Plt;0.05). Among them, TSH level was independently associated with HB and positively correlated with HI score (r=0.668, Plt;0.001). Additionally, TSH level had a certain value in distinguishing ADHD children with HB, with a cut-off point of 2.57 μIU/ml (sensitivity was 65.1%, specificity was 74.7%). Conclusion This study revealed a positive correlation between serum TSH level and HB in children with ADHD, and it can be used to differentiate ADHD children with HB.
[Key words] Attention deficit hyperactivity disorder; Hyperactivity index; Thyroid stimulating hormone
注意缺陷多動(dòng)障礙(attention deficit hyperactivity disorder,ADHD)是一種常見(jiàn)的具有損害性質(zhì)的疾病,常伴隨其他精神障礙共病,給患者、家庭和社會(huì)帶來(lái)沉重負(fù)擔(dān)[1]。ADHD的遺傳性很高,約80%;許多環(huán)境暴露與ADHD相關(guān),社會(huì)因素對(duì)其發(fā)生也存在影響[2-4]。研究顯示暴露于人工食品色素可增加ADHD癥狀的嚴(yán)重程度[5]。多種因素導(dǎo)致ADHD發(fā)病率增加,據(jù)估計(jì),ADHD的全球發(fā)病率為2%~7%[6];在中國(guó)6~16歲的兒童中有6.2%~7.0%的ADHD患者[7]。然而,除一些用于治療特定癥狀的藥物外,目前還沒(méi)有針對(duì)ADHD的整體治療方法[8]。為改善這種現(xiàn)狀,更好地了解導(dǎo)致ADHD風(fēng)險(xiǎn)增加的潛在因素尤為重要。
甲狀腺功能狀態(tài)對(duì)運(yùn)動(dòng)、認(rèn)知和情感活動(dòng)控制至關(guān)重要[9-10];游離三碘甲狀腺原氨酸(triiodothyronine,F(xiàn)T3)、游離甲狀腺素(free thyroxine,F(xiàn)T4)和促甲狀腺激素(thyroid stimulating hormone,TSH)三者決定甲狀腺的功能狀態(tài)。與ADHD類(lèi)似的癥狀,包括焦慮、緊張、易怒和身體過(guò)度活動(dòng)等,與甲狀腺功能亢進(jìn)有關(guān)[11]。此外,研究表明母體的甲狀腺功能亢進(jìn)、妊娠期間高TSH濃度及早期妊娠母體的自身免疫性甲狀腺炎等均可增加后代患ADHD的風(fēng)險(xiǎn)[12-14]。這些發(fā)現(xiàn)表明甲狀腺功能障礙與兒童ADHD之間可能存在關(guān)聯(lián)。然而,生理范圍內(nèi)的FT3、FT4和TSH與兒童ADHD癥狀之間的關(guān)系缺乏研究。本研究旨在探討甲狀腺功能與ADHD兒童的多動(dòng)行為(hyperactivity behavior,HB)之間的關(guān)系,進(jìn)一步了解導(dǎo)致ADHD風(fēng)險(xiǎn)增加的潛在因素,為兒童ADHD的治療提供參考。
1 "資料與方法
1.1" 一般資料
選取2018年2月至2023年8月于湖州市中心醫(yī)院治療并隨訪的134例ADHD患兒作為研究對(duì)象,診斷標(biāo)準(zhǔn)符合《注意缺陷多動(dòng)障礙早期識(shí)別、規(guī)范診斷和治療的兒科專(zhuān)家共識(shí)》[15]中關(guān)于ADHD的要求。納入標(biāo)準(zhǔn):①符合上述診斷標(biāo)準(zhǔn),年齡6~14歲;②智商評(píng)分gt;80分;③未接受任何ADHD治療。排除標(biāo)準(zhǔn):①患有神經(jīng)及發(fā)育障礙性疾病的患兒,如癲癇、自身免疫性腦炎、腦性癱瘓、抽動(dòng)障礙、腦白質(zhì)營(yíng)養(yǎng)不良等;②患有嚴(yán)重身體疾病的患兒,如聽(tīng)力損害、視力損害、甲狀腺功能異常、阻塞性睡眠呼吸暫停等;③患有其他精神心理障礙的患兒,如精神分裂癥、抑郁癥和兒童雙相障礙等;④有嚴(yán)重腦外傷史的患兒;⑤有遺傳性疾病的患兒,如脆性X綜合征、Tunner綜合征和神經(jīng)纖維瘤等;⑥出生胎齡lt;32周或出生體質(zhì)量lt;1500g或Apgar評(píng)分lt;7分的患兒。根據(jù)Conners父母癥狀量表(parent symptom questionnaire,PSQ)的多動(dòng)指數(shù)
(hyperactivity index,HI)[16]將納入的ADHD患兒分為兩組。非HB組:沒(méi)有HB,HIlt;1.5,共71例,其中男55例(77.5%),平均年齡(8.0±0.3)歲;HB組:具有HB,HIgt;1.5,共63例,其中男48例(76.2%),平均年齡(7.9±0.3)歲。兩組患兒的性別、年齡、出生史、分娩方式、胎齡、出生體質(zhì)量、環(huán)境暴露史、飲食習(xí)慣、家庭環(huán)境、家族史比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05),具有可比性,見(jiàn)表1。本研究經(jīng)湖州市中心醫(yī)院醫(yī)學(xué)倫理委員會(huì)審批通過(guò)(倫理審批號(hào):202411009-01)。
1.2" 方法
對(duì)患兒進(jìn)行回顧性研究,使用電子病歷獲取患兒的臨床和實(shí)驗(yàn)室數(shù)據(jù):性別、年齡、出生史、分娩方式、胎齡、出生體質(zhì)量、環(huán)境暴露史、飲食習(xí)慣、家庭環(huán)境、家族史等一般情況,及丙氨酸轉(zhuǎn)氨酶(alanine amiotransferase,ALT)、天冬氨酸轉(zhuǎn)氨酶(aspartate transaminase,AST)、總蛋白(total protein,TP)、血尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)、乳酸(lactate,Lac)、血清鐵蛋白(serum ferritin,SF)、FT3、FT4、TSH等。患兒在采血前24h內(nèi)避免運(yùn)動(dòng)和飲酒,不改變飲食習(xí)慣和睡眠習(xí)慣,禁食12h后空腹采血。ALT、AST、TP、BUN、Cr測(cè)定:采血于含促凝劑的真空管,立即送至檢驗(yàn)科,設(shè)備為ABBOTT C16000全自動(dòng)生化分析儀。采用國(guó)際臨床化學(xué)學(xué)會(huì)推薦的紫外連續(xù)監(jiān)測(cè)法,使用ABBOTT公司的ALT測(cè)定試劑盒、AST測(cè)定試劑盒測(cè)定ALT、AST;采用雙縮脲法,使用ABBOTT公司TP測(cè)定試劑盒測(cè)定TP;采用國(guó)際臨床化學(xué)學(xué)會(huì)推薦的尿素酶法和堿性苦味酸法,使用雅培的配套試劑測(cè)定BUN、Cr。SF、FT3、FT4、TSH測(cè)定:常規(guī)靜脈采血約2ml,不抗凝,置普通試管中立即送至檢驗(yàn)科,設(shè)備為美國(guó)雅培公司的ARCHITECTi2000發(fā)光免疫分析儀;采用兩步免疫法,使用美國(guó)雅培公司出品的SF測(cè)定試劑包測(cè)定SF;采用化學(xué)發(fā)光微粒子免疫分析原理,使用ARCHITECT FT3測(cè)定試劑包(美國(guó)雅培公司,試劑盒產(chǎn)品號(hào)7K63-30)、ARCHITECTFT4測(cè)定試劑包(美國(guó)雅培公司,試劑盒產(chǎn)品號(hào)6C50-24)、ARCHITECT TSH測(cè)定試劑包(美國(guó)雅培公司,試劑盒產(chǎn)品號(hào)7K62-30)測(cè)定FT3、FT4、TSH。Lac使用ABL-800血?dú)夥治鰞x進(jìn)行檢測(cè)。
1.3" 統(tǒng)計(jì)學(xué)方法
采用SPSS 22.0統(tǒng)計(jì)學(xué)軟件對(duì)數(shù)據(jù)進(jìn)行處理分析。符合正態(tài)分布的計(jì)量資料以均數(shù)±標(biāo)準(zhǔn)差(
)表示,比較采用獨(dú)立樣本t檢驗(yàn);計(jì)數(shù)資料以例數(shù)(百分率)[n(%)]表示,比較采用c2檢驗(yàn);符合正態(tài)分布的變量間相關(guān)性采用Pearson直線相關(guān)分析;使用受試者操作特征曲線(receiver operating characteristic curve,ROC曲線)分析各指標(biāo)的診斷價(jià)值。Plt;0.05為差異有統(tǒng)計(jì)學(xué)意義。
2" 結(jié)果
2.1 "兩組患兒的實(shí)驗(yàn)室指標(biāo)比較
HB組患兒的Lac、TSH高于非HB組,差異有統(tǒng)計(jì)學(xué)意義(Plt;0.05)。兩組患兒的其他實(shí)驗(yàn)室指標(biāo)比較,差異無(wú)統(tǒng)計(jì)學(xué)意義(Pgt;0.05),見(jiàn)表2。
2.2" HB相關(guān)因素的二分類(lèi)Logistic回歸分析
將單因素分析中P≤0.15的變量(AST、Lac、SF、FT3和TSH)納入二元Logistics回歸模型中評(píng)估與HB相關(guān)的因素。結(jié)果顯示TSH與HB呈獨(dú)立正相關(guān),見(jiàn)表3。
2.3 "血清TSH水平與Conners PSQ HI得分的相關(guān)性
通過(guò)Pearson直線相關(guān)分析發(fā)現(xiàn),TSH水平與HI得分呈正相關(guān)(r=0.668,Plt;0.001),見(jiàn)圖1。

2.4 "血清TSH水平區(qū)分ADHD患兒HB的潛在診斷價(jià)值
ROC曲線分析顯示血清TSH水平區(qū)分ADHD患兒HB的截?cái)嘀禐?.57μIU/ml(曲線下面積為0.720,95%CI:0.636~0.794,Plt;0.001,約登指數(shù)0.3973,敏感度65.08%,特異性74.65%),見(jiàn)圖2。

3" 討論
ADHD經(jīng)常與其他精神障礙同時(shí)存在,藥物治療策略在短期內(nèi)已被證明有效且低成本[17]。然而,這些治療對(duì)關(guān)鍵的教育、職業(yè)和社交結(jié)果的長(zhǎng)期有效性尚不確定,且這些效果受低依從性的影響。所以對(duì)ADHD患兒需要更好的長(zhǎng)期治療方法。而通過(guò)改變對(duì)ADHD成因的認(rèn)識(shí)有助于開(kāi)發(fā)提高當(dāng)前治療效果或發(fā)展新的替代方法。
甲狀腺激素在中樞神經(jīng)系統(tǒng)的發(fā)育中發(fā)揮重要作用。在早期發(fā)育階段,胎兒由于自身甲狀腺功能障礙,依賴(lài)于母體甲狀腺激素的產(chǎn)生[18]。因此,母體甲狀腺功能障礙可引發(fā)后代神經(jīng)發(fā)育、神經(jīng)化學(xué)和行為方面的顯著異常,對(duì)兒童神經(jīng)發(fā)育結(jié)果產(chǎn)生不良影響[19]。研究顯示高濃度和低濃度的母親甲狀腺激素均可增加后代患ADHD的風(fēng)險(xiǎn)[20]。此外,還發(fā)現(xiàn)高水平的甲狀腺激素可能對(duì)神經(jīng)發(fā)育結(jié)果產(chǎn)生不良影響[21]。然而,在正常范圍內(nèi)的甲狀腺激素對(duì)行為和智力能力的具體影響尚不明確,與ADHD患兒癥狀之間的關(guān)系仍不明確。甲狀腺功能可通過(guò)直接測(cè)量FT4或間接評(píng)估TSH濃度確定,后者反映垂體感知的甲狀腺激素濃度[22]。事實(shí)上,與FT4測(cè)試相比,血清TSH測(cè)量對(duì)檢測(cè)甲狀腺功能障礙具有更好的敏感度,因?yàn)檠錞SH和FT4濃度呈反比對(duì)數(shù)關(guān)系,F(xiàn)T4的微小變化可引起血清TSH更大的反應(yīng)[23]。另外,實(shí)驗(yàn)室參考范圍內(nèi)的甲狀腺激素濃度不一定適用于個(gè)體,如亞臨床甲狀腺功能減退是一種以TSH濃度超過(guò)參考范圍、FT4和FT3濃度在參考范圍內(nèi)為特征的臨床疾病[24];該類(lèi)患者的血清TSH超出參考范圍,表明在參考范圍內(nèi)的血清FT3和FT4對(duì)該個(gè)體來(lái)說(shuō)并不正常。
Conners PSQ是一種用于評(píng)估與ADHD和相關(guān)障礙有關(guān)的行為問(wèn)題的家長(zhǎng)問(wèn)卷[25]。由于其良好的可靠性和效度,被廣泛用于評(píng)估ADHD相關(guān)的癥狀。因此,本研究選擇該量表評(píng)估與ADHD相關(guān)的癥狀。本研究中TSH水平與Conners PSQ HI得分呈正相關(guān),提示TSH可能與ADHD癥狀嚴(yán)重程度,特別是與HB有關(guān)。Alvarez-Pedrerol等[26]研究發(fā)現(xiàn)高濃度的TSH與記憶、語(yǔ)言和數(shù)量技能呈負(fù)相關(guān),與注意力缺陷和多動(dòng)/沖動(dòng)癥狀呈正相關(guān);但2017年印度一項(xiàng)研究發(fā)現(xiàn),血清TSH水平與ADHD癥狀之間無(wú)顯著相關(guān)性[27]。這些差異歸因于所研究的人群和性別比例的不同。
本研究進(jìn)一步探討TSH作為ADHD中HB的診斷生物標(biāo)志物的潛在價(jià)值,認(rèn)為T(mén)SH水平可用于區(qū)分患HB的ADHD兒童和未患HB的ADHD兒童;這與Chen等[28]研究結(jié)果一致。這些發(fā)現(xiàn)進(jìn)一步證實(shí)TSH與ADHD兒童的HB之間的密切關(guān)系。
本研究發(fā)現(xiàn)與無(wú)HB的ADHD兒童相比,患有HB的ADHD兒童的Lac水平較高。可能由于患有HB的ADHD兒童活動(dòng)過(guò)度,導(dǎo)致血清中Lac積累。這種關(guān)系有待進(jìn)一步研究確認(rèn)。
綜上所述,本研究揭示血清TSH水平與ADHD兒童的HB有關(guān),可用于區(qū)分ADHD兒童的HB。為進(jìn)一步驗(yàn)證該結(jié)論,需要進(jìn)行多中心研究,并進(jìn)行縱向研究和隨機(jī)對(duì)照試驗(yàn)以檢驗(yàn)甲狀腺功能與ADHD兒童癥狀之間的因果關(guān)系,同時(shí),探討飲食、生活習(xí)慣、環(huán)境暴露等其他可能影響ADHD和甲狀腺功能的因素。
利益沖突:所有作者均聲明不存在利益沖突。
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(收稿日期:2024–10–07)
(修回日期:2024–12–23)
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