Raux Demay M C, Magny J P, Idrès N, Grimfeld A, Le Bouc Y
Laboratoire d'Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau (APHP), Paris, France.
Horm Res. 2006;66(2):51-60. doi: 10.1159/000093468. Epub 2006 May 19.
Subnormal hypothalamic-pituitary-adrenal (HPA) function and rare cases of adrenal crisis have been reported in asthmatic children treated with inhaled corticosteroids. We investigated subnormal HPA activity and followed up affected patients until recovery of normal HPA functions.
100 children with persistent asthma underwent low-dose corticotropin testing, with the administration of 1 microg of 1-24 ACTH intravenously. Treatments were beclomethasone dipropionate as a metered-dose inhaler, n = 14, budesonide as a dry-powder inhaler, n = 16, fluticasone propionate as a metered-dose inhaler n = 31 or a dry-powder inhaler n = 39. The mean commercially labelled dose was 520 +/- 29 microg/day (mean +/- SEM, range: 160-1,000) and the equipotent dose (which compares the efficiency of these drugs for treating asthma and their responsibility for systemic effects) was 890 +/- 55 microg/day (range: 200-2,000).
The mean stimulated cortisol level +/- SEM (and range) of the patient was 482 +/- 12 (148-801), and that of 40 age-matched controls was 580 +/- 12.5 (439-726), (SD = 79). The result was subnormal (more than 2 SD below the mean of the controls) in28 of the 100 patients. One-four stepwise decreases of 10-100% in the daily equipotent doses received by the patients with abnormal low-dose corticotropin testing results led to normal results in subsequent low-dose corticotropin testing in 27 retested patients. The mean time interval between two tests was 5 months (range: 2-6 months) and the mean period required for normalization of the test was 13 months (range: 2-21). Only one case of asthma exacerbation and no adrenal crisis were observed over these periods.
Decreasing daily equipotent doses led to recovery of normal HPA function without asthma exacerbation. Thus, a revision of the doses of inhaled corticosteroids used in asthmatic children with a progressive decrease to the consensus-recommended doses should decrease the systemic effects of inhaled corticosteroids, while minimizing the risk of asthma exacerbation.
有报道称，接受吸入性糖皮质激素治疗的哮喘儿童存在下丘脑 - 垂体 - 肾上腺（HPA）功能减退以及罕见的肾上腺危象病例。我们对HPA活性减退情况进行了调查，并对受影响的患者进行随访直至HPA功能恢复正常。
100例持续性哮喘儿童接受了低剂量促肾上腺皮质激素试验，静脉注射1微克1 - 24促肾上腺皮质激素（ACTH）。治疗药物为丙酸倍氯米松定量气雾剂（n = 14）、布地奈德干粉吸入剂（n = 16）、丙酸氟替卡松定量气雾剂（n = 31）或干粉吸入剂（n = 39）。平均商业标注剂量为520±29微克/天（均值±标准误，范围：160 - 1000），等效剂量（用于比较这些药物治疗哮喘的效果及其全身效应）为890±55微克/天（范围：200 - 2000）。
患者刺激后皮质醇水平的均值±标准误（及范围）为482±12（148 - 801），40例年龄匹配的对照组为580±12.5（439 - 726），（标准差 = 79）。100例患者中有28例结果低于正常（比对照组均值低2个标准差以上）。低剂量促肾上腺皮质激素试验结果异常的患者，每日等效剂量逐步降低10% - 100%，其中27例再次检测的患者在后续低剂量促肾上腺皮质激素试验中结果恢复正常。两次检测的平均时间间隔为5个月（范围：2 - 6个月），检测结果恢复正常所需的平均时间为13个月（范围：2 - 21个月）。在此期间仅观察到1例哮喘加重，未发生肾上腺危象。
每日等效剂量降低可使HPA功能恢复正常，且无哮喘加重情况。因此，对于哮喘儿童，逐步降低吸入性糖皮质激素剂量至共识推荐剂量，应可降低吸入性糖皮质激素的全身效应，同时将哮喘加重的风险降至最低。
