HYPOTHALAMO-PITUITARY-ADRENAL AXIS SUPPRESSION IN ASTHMATICS INHALING HIGH-DOSE CORTICOSTEROIDS

The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose (> 1000 μg daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600 μg, range 1200–2650 μg 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 μg, n = 36; 2000 μg, n = 26, > 2000 μg, n = 7) and nine budesonide (1200 μg, n = 2; 1600 μg, n = 6; 1800 μg, n = 1). Four patients, all of whom were taking > 2000 μg beclomethasone dipropionate, were taking 200–400 μg 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 < 190 nmol 1−1; rise in serum cortisol in response to tetracosactrin < 200 nmol 1−1 and/or achieved cortisol < 500 nmol 1−1; urine free cortisol < 80 nmol 24h−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 μg, n = 6; 1600 μg, n = 1; 2000 μg, n = 7; 2400 μg, n = 2). Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, χ2 = 6·1, P < 0·02); and (b) increasing duration of high dose inhaled therapy (median 28·5 months in suppressed vs. 12 months in normal, P < 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 ≥ 1500 μg inhaled corticosteroid daily. Unless function has been shown to be normal, all patients taking these doses should carry steroid cards. © 1991, Baillière Tindall All rights reserved. All rights reserved.