皮质激素吸入和鼻腔给药对哮喘患儿下丘脑-垂体-肾上腺轴的抑制：早晨血清促肾上腺皮质激素（ACTH）的
2011/10/13
摘要
背景：采用皮质激素吸入(ICS)联合或不联合鼻腔皮质激素（NS）治疗的哮喘患者，其下丘脑-垂体-肾上腺抑制(HPAS)比想象的更为常见。唯有动态监测才有可能发现患儿的肾上腺危象风险。但对于所有哮喘患者采用标准肾上腺功能试验（如美替拉酮或胰岛素耐受试验）来检测HPAS并不实际。
目的：研究哪些临床和生化指标可用于哮喘患儿的HPAS的筛查。
方法：26名年龄为5～18岁、过去1年中采用ICS ± NS、但无口服和外用激素的哮喘患者入选。记录身高、体重、身高增长速率、体重增加速率和卧位至直立位后的收缩压变化(ΔSBP)。收集早晨尿液，检查尿游离可的松（UFC）和尿可的松代谢物（UCM）。UFC 采用化学发光分析和气相色谱/质谱(GC-MS)。同时检测早晨血清可的松和促肾上腺皮质激素(ACTH)水平。 如果早晨空腹血清可的松>83 nmol/l，则进行隔夜美替拉酮试验。美替拉酮试验后ACTH增加不能>100 pg/ml则诊断为HPAS。计算美替拉酮试验后ACTH与各指标间相关性的斯皮尔曼相关系数。依据以上测试绘制受试者工作特征（ROC）曲线，并计算诊断效能。
结果：所有临床和生化指标与美替拉酮试验后ACTH相关性较弱或无相关性，但与早晨血清ACTH相关（r = 0.68; p <0.00）。那些存在HPAS和无HPAS的受试者中，最好的鉴别指标是早晨血清ACTH水平为11.7 pg/ml，其鉴别的敏感性为0.89（0.57-0.98），特异性为0.77 (0.53-0.90)，阳性预测值为0.67 (0.39-0.87)，阴性预测值为0.93 (0.69-0.99)，准确率为0.81 (0.61-0.94)，阳性似然比为3.78 (1.68-9.49)，阴性似然比为0.15 (0.03-0.60)。
结论：早晨血清ACTH水平是检测哮喘患儿接受ICS ± NS治疗后是否存在HPAS的最有用的筛查方法。早晨血清ACTH水平的诊断精准确性有必要通过大样本研究进行进一步验证。
（刘国梁 审校）
Pediatr Allergy Immunol. 2011 Jul 28. doi: 10.1111/j.1399-3038.2011.01161.x. [Epub ahead of print]
Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?
Zöllner EW, Lombard C, Galal U, Hough S, Irusen E, Weinberg E.
Source
Paediatric Endocrine Unit, Tygerberg Children’s Hospital, University of Stellenbosch, Cape Town, South Africa (formerly Endocrine Unit, Red Cross Children’s Hospital, University of Cape Town, Cape Town, South Africa) Biostatistics Unit, Medical Research Council, Cape Town, South Africa Department of Medicine, Endocrine Unit, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa Pulmonology Division, Department of Medicine, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa Allergy Unit, Red Cross Children’s Hospital, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test.
OBJECTIVE: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children.
METHODS: Twenty-six asthmatic children, 5-18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated.
RESULTS: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p <0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7 pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60).
CONCLUSIONS: The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS ± NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level.
Pediatr Allergy Immunol. 2011 Jul 28. doi: 10.1111/j.1399-3038.2011.01161.x. [Epub ahead of print]
背景：采用皮质激素吸入(ICS)联合或不联合鼻腔皮质激素（NS）治疗的哮喘患者，其下丘脑-垂体-肾上腺抑制(HPAS)比想象的更为常见。唯有动态监测才有可能发现患儿的肾上腺危象风险。但对于所有哮喘患者采用标准肾上腺功能试验（如美替拉酮或胰岛素耐受试验）来检测HPAS并不实际。
目的：研究哪些临床和生化指标可用于哮喘患儿的HPAS的筛查。
方法：26名年龄为5～18岁、过去1年中采用ICS ± NS、但无口服和外用激素的哮喘患者入选。记录身高、体重、身高增长速率、体重增加速率和卧位至直立位后的收缩压变化(ΔSBP)。收集早晨尿液，检查尿游离可的松（UFC）和尿可的松代谢物（UCM）。UFC 采用化学发光分析和气相色谱/质谱(GC-MS)。同时检测早晨血清可的松和促肾上腺皮质激素(ACTH)水平。 如果早晨空腹血清可的松>83 nmol/l，则进行隔夜美替拉酮试验。美替拉酮试验后ACTH增加不能>100 pg/ml则诊断为HPAS。计算美替拉酮试验后ACTH与各指标间相关性的斯皮尔曼相关系数。依据以上测试绘制受试者工作特征（ROC）曲线，并计算诊断效能。
结果：所有临床和生化指标与美替拉酮试验后ACTH相关性较弱或无相关性，但与早晨血清ACTH相关（r = 0.68; p <0.00）。那些存在HPAS和无HPAS的受试者中，最好的鉴别指标是早晨血清ACTH水平为11.7 pg/ml，其鉴别的敏感性为0.89（0.57-0.98），特异性为0.77 (0.53-0.90)，阳性预测值为0.67 (0.39-0.87)，阴性预测值为0.93 (0.69-0.99)，准确率为0.81 (0.61-0.94)，阳性似然比为3.78 (1.68-9.49)，阴性似然比为0.15 (0.03-0.60)。
结论：早晨血清ACTH水平是检测哮喘患儿接受ICS ± NS治疗后是否存在HPAS的最有用的筛查方法。早晨血清ACTH水平的诊断精准确性有必要通过大样本研究进行进一步验证。
（刘国梁 审校）
Pediatr Allergy Immunol. 2011 Jul 28. doi: 10.1111/j.1399-3038.2011.01161.x. [Epub ahead of print]
Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?
Zöllner EW, Lombard C, Galal U, Hough S, Irusen E, Weinberg E.
Source
Paediatric Endocrine Unit, Tygerberg Children’s Hospital, University of Stellenbosch, Cape Town, South Africa (formerly Endocrine Unit, Red Cross Children’s Hospital, University of Cape Town, Cape Town, South Africa) Biostatistics Unit, Medical Research Council, Cape Town, South Africa Department of Medicine, Endocrine Unit, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa Pulmonology Division, Department of Medicine, Tygerberg Hospital, University of Stellenbosch, Cape Town, South Africa Allergy Unit, Red Cross Children’s Hospital, University of Cape Town, Cape Town, South Africa.
Abstract
BACKGROUND: Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test.
OBJECTIVE: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children.
METHODS: Twenty-six asthmatic children, 5-18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated.
RESULTS: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p <0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7 pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60).
CONCLUSIONS: The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS ± NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level.
Pediatr Allergy Immunol. 2011 Jul 28. doi: 10.1111/j.1399-3038.2011.01161.x. [Epub ahead of print]
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大部分夜间哮喘症状出现在哮喘急性发作期以外且与哮喘发病相关
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儿童哮喘重度发作的相关因素
