血清皮质醇作为生物标志物在注意缺陷多动障碍诊断中的价值

Clinical value of serum cortisol as a biomarker in the diagnosis of attention deficit hyperactivity disorder

目的通过了解血清皮质醇水平与注意缺陷多动障碍(ADHD)的关系,探讨其在ADHD诊断中的应用和临床意义,为将来ADHD的综合防治提供线索和理论依据。方法对2018年7月至2019年6月在福建医科大学附属协和医院确诊的159例ADHD患儿[ADHD组,其中注意缺陷为主型(ADHD-I)58例,多动冲动为主型(ADHD-HI)32例,混合型(ADHD-C)69例]及58例健康对照儿童(健康对照组)进行血清皮质醇水平检测,采用受试者工作特征曲线(ROC)评估血清皮质醇水平对ADHD各组的诊断价值。结果1.ADHD-I组[(216.58±70.55)nmol/L]、ADHD-HI组[(182.26±51.34)nmol/L]和ADHD-C组[(222.81±75.70)nmol/L]血清皮质醇水平均明显低于健康对照组[(344.83±98.17)nmol/L](均P<0.001);ADHD-HI组皮质醇水平低于ADHD-I组和ADHD-C组(P<0.05)。ADHD-I组与ADHD-C组皮质醇水平比较差异无统计学意义(P>0.05)。2.ROC曲线显示,血清皮质醇水平诊断ADHD组的ROC曲线下面积为0.866(95%CI:0.814~0.917),Youden指数最大值为0.583,对应敏感性为89.3%,特异性为69.0%,皮质醇水平最佳临界值为302.88 nmol/L,246.13 nmol/L是特异性为85.0%时的诊断阈值,其对应敏感性为71.1%;皮质醇水平诊断ADHD-I组的ROC曲线下面积为0.857(95%CI:0.792~0.922),Youden指数最大值为0.552,对应敏感性为69.0%,特异性为86.2%,最佳临界值为243.39 nmol/L;皮质醇水平诊断ADHD-HI组的ROC曲线下面积为0.934(95%CI:0.887~0.980),Youden指数最大值为0.745,对应敏感性96.9%,特异性为77.6%,最佳临界值为261.55 nmol/L;皮质醇水平诊断ADHD-C组的ROC曲线下面积为0.841(95%CI:0.774~0.908),Youden指数最大值为0.559,对应敏感性为87.0%,特异性为69.0%,最佳临界值为302.82 nmol/L。鉴于家长对ADHD行为认识不足,建议按85.0%特异性原则,将皮质醇水平246.13 nmol/L作为诊断阈值,在临床上结合行为核查,以提高诊断精准率。结论ADHD与ADHD各亚型儿童血清基础皮质醇水平均低于健康儿童,下丘脑-垂体-肾上腺轴应激反应低下。皮质醇水平在诊断ADHD时具有一定准确性,可应用于临床诊断。

Objective To explore the relationship between serum cortisol and attention deficit hyperactivity disorder(ADHD),and to investigate the application of cortisol in the diagnosis of ADHD,so as to provide clues and theoretical basis for the comprehensive prevention and treatment of ADHD in the future.Methods Serum cortisol levels were detected in 159 ADHD children[ADHD group,58 cases of predominately inattentive presentation(ADHD-I),32 cases of predominately hyperactive/impulsive presentation(ADHD-HI),69 cases of combined presentation(ADHD-C)],and 58 healthy control children(healthy control group)from July 2018 to June 2019,at Fujian Medical University Union Hospital.The receiver operating characteristic(ROC)was used to evaluate the diagnostic value of serum cortisol levels in ADHD groups.Results(1)The serum cortisol levels of ADHD-I group[(216.58±70.55)nmol/L],ADHD-HI group[(182.26±51.34)nmol/L]and ADHD-C group[(222.81±75.70)nmol/L]were significantly lower than that of the healthy control group[(344.83±98.17)nmol/L](all P<0.001).The level of cortisol in ADHD-HI group was lower than that in ADHD-I group and ADHD-C group(P<0.05).(2)According to the ROC analysis of serum cortisol,the area under the ROC curve for the diagnosis of ADHD group was 0.866(95%CI:0.814-0.917),the maximum Youden index was 0.583,the corresponding sensitivity was 89.3%,the specificity was 69.0%,and the cut-off was 302.88 nmol/L.When the specificity was 85.0%,246.13 nmol/L was the diagnostic threshold and its corresponding sensitivity was 71.1%.Under the ROC curve for the diagnosis of ADHD-I group,the area was 0.857(95%CI:0.792-0.922),the maximum Youden index was 0.552,the corresponding sensitivity was 69.0%,the specificity was 86.2%,and the cut-off was 243.39 nmol/L.Under the ROC curve for the diagnosis of ADHD-HI group,the area was 0.934(95%CI:0.887-0.980),the maximum Youden index was 0.745,the corresponding sensitivity was 96.9%,the specificity was 77.6%,and the cut-off was 261.55 nmol/L.Under the ROC curve for the diagnosis of ADHD-C group,the area was 0.841(95%CI:0.774-0.908),the maximum Youden index was 0.559,the corresponding sensitivity was 87.0%,the specificity was 69.0%,and the cut-off was 302.82 nmol/L.In view of parents′lack of understanding of ADHD behavior,it is suggested that the diagnostic threshold of cortisol level of 246.13 nmol/L should be based on 85.0%specificity principle,combined with behavior verification in clinical practice,so as to improve the diagnostic accuracy.Conclusions Cortisol levels in ADHD-I,ADHD-HI and ADHD-C groups are lower than that in control group.There is functional impairment of hypothalamic-pituitary-adrenal axis in ADHD children.The level of cortisol has certain accuracy in the diagnosis of simple ADHD and can be used in clinical diagnosis.