Brown P H, Blundell G, Greening A P, Crompton G K
Department of Respiratory Medicine, Northern General Hospital, Edinburgh, U.K.
Respir Med. 1991 Nov;85(6):501-10. doi: 10.1016/s0954-6111(06)80268-4.
The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (greater than 1000 micrograms daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 micrograms, range 1200-2650 micrograms daily). All patients except one were using metered dose aerosols; 15 were using large volume spacer devices. Median duration of high dose therapy was 13 months (range 1-54). Sixty-nine patients were taking beclomethasone dipropionate (1500 micrograms, n = 36; 2000 micrograms, n = 26, greater than 2000 micrograms, n = 7) and nine budesonide (1200 micrograms, n = 2; 1600 micrograms, n = 6; 1800 micrograms, n = 1). Four patients, all of whom were taking greater than 2000 micrograms beclomethasone dipropionate, were taking 200-400 micrograms of their total dose intranasally. Twenty-six patients had discontinued long term systemic corticosteroid treatment (at least 5 mg prednisolone daily, or equivalent, for a minimum of 6 months) between 7 months and 22 years prior to assessment. All patients had measurements of 9 am serum cortisol and 24-h urine free cortisol excretion and a short tetracosactrin test. Subnormal results were: 9 am cortisol less than 190 nmol l-1; rise in serum cortisol in response to tetracosactrin less than 200 nmol l-1 and/or achieved cortisol less than 500 nmol l-1; urine free cortisol less than 80 nmol 24 h-1. Hypothalamo-pituitary-adrenal suppression was defined as subnormal results in at least two of the three tests. Tests were performed at least 2 weeks after completion of any short course prednisolone treatments. Suppression was found in 16 (20.5%) patients (1500 micrograms, n = 6; 1600 micrograms, n = 1; 2000 micrograms, n = 7; 2400 micrograms, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, chi 2 = 6.1, P less than 0.02); and (b) increasing duration of high dose inhaled therapy (median 28.5 months in suppressed vs. 12 months in normal, P less than 0.05). No clear relationship was identified between HPA function and dose, even when corrected for body surface area and there was no relationship between suppression and number of short courses of prednisolone in the preceding 12 months. Screening tests of HPA function should be performed in all asthmatics taking greater than or equal to 1500 micrograms inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards.
服用高剂量（每日超过1000微克）吸入性皮质类固醇的哮喘患者下丘脑-垂体-肾上腺（HPA）轴抑制的频率尚不清楚。对78名长期吸入皮质类固醇（中位剂量1600微克，范围为每日1200 - 2650微克）的成年哮喘患者的HPA功能进行了研究。除1名患者外，所有患者均使用定量气雾剂；15名患者使用大容量储雾罐装置。高剂量治疗的中位持续时间为13个月（范围为1 - 54个月）。69名患者服用二丙酸倍氯米松（1500微克，n = 36；2000微克，n = 26，大于2000微克，n = 7），9名患者服用布地奈德（1200微克，n = 2；1600微克，n = 6；1800微克，n = 1）。4名患者，均服用大于2000微克的二丙酸倍氯米松，其总剂量的200 - 400微克经鼻给药。26名患者在评估前7个月至22年期间已停止长期全身皮质类固醇治疗（至少每日5毫克泼尼松龙或等效药物，至少持续6个月）。所有患者均测量了上午9点的血清皮质醇、24小时尿游离皮质醇排泄量，并进行了短程二十四肽促皮质素试验。异常结果为：上午9点皮质醇低于190 nmol/L；对二十四肽促皮质素反应的血清皮质醇升高低于200 nmol/L和/或达到的皮质醇低于500 nmol/L；尿游离皮质醇低于80 nmol/24小时。HPA轴抑制定义为三项试验中至少两项结果异常。在完成任何短程泼尼松龙治疗至少2周后进行试验。16名（20.5%）患者出现抑制（1500微克，n = 6；1600微克，n = 1；2000微克，n = 7；2400微克，n = 2）。确定的这种抑制的危险因素为：（a）先前需要长期全身皮质类固醇治疗（10/26，卡方 = 6.1，P < 0.02）；（b）高剂量吸入治疗持续时间增加（抑制患者中位时间为28.5个月，正常患者为12个月，P < 0.05）。即使校正体表面积后，HPA功能与剂量之间也未发现明确关系，且抑制与前12个月内泼尼松龙短程治疗次数之间也无关系。所有每日吸入皮质类固醇大于或等于1500微克的哮喘患者均应进行HPA功能筛查试验。除非已证明功能正常，所有服用这些剂量的患者均应携带类固醇卡片。
