Respiratory Medicine ( 1991 ) 85, 50 I-510
Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids P. H.
BROWN,G. BLUNDELL*,A. P. GREENINGAND G. K. CROMPTON
Departments of Respiratory Medicine and *Clinical Chemistry, Northern and Western General Hospitals, Edinburgh, U.K.
The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose ( > 1000 pg daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600/tg, range 1200-2650/tg 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/,tg, n = 36; 2000/zg, n = 26, > 2000 fig, n = 7) and nine budesonide (1200/zg, n = 2; 1600 pg, n = 6; 1800 pg, n = 1). Four patients, all of whom were taking > 2000 pg beclomethasone dipropionate, were taking 200-400 pg 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-~; rise in serum cortisol in response to tetracosactrin < 200 nmol 1-~ and/or achieved cortisol < 500 nmol I- I; urine free cortisol < 80 nmol 24 h - ~. 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°,/o) patients (1500 pg, n = 6 ; 1600pg, n = 1; 2000/zg, n = 7 ; 2400/tg, n = 2 ) . Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, Z-~=6-1, P 2 0 0 0 p.g BDP (n=7)
Dose of inholed steroid
Fig. 1 9am serum cortisol and response to tetracosactrin i~ asthmatics (n=78) inhaling high dose beclomethasone dipropionate (BDP) or budesonide (BUD). S, Patients using 750-ml spacer devices.
this subgroup analysis as she had required three short courses of prednisolone in the preceding 12 months, the last of these being 1 month prior to tests. She showed no clinical features of cortisol excess, had normal 24-h urine free cortisol excretion and showed normal suppression of serum cortisol in response to an overnight dexamethasone suppression test.
EFFECT OF SHORT COURSES OF PREDNISOLONE
Twenty-four (30.8%) patients had required three or more (maximum six) short courses o f prednisolone in the preceding year. Five of these patients had HPA suppression, three of whom had formerly been taking long-term prednisolone. Of nine patients with a history of long-term and frequent short-term prednisolone therapy, six had normal axis function. Of 14 patients who completed a short course between 2 and 4 weeks prior to assessment, ten had normal axis function. Multiple logistic regression analysis did not show that the number of courses of prednisolone contributed independently to HPA suppression.
EFFECT OF DURATION OF H I G H DOSE INHALED STEROID THERAPY
The 16 patients with H P A suppression had been taking high dose inhaled corticosteroid therapy significantly longer than those with normal function (median 28.5 months vs. 12 months; P
Hypothalamo-pituitary-adrenal axis suppression in asthmatics inhaling high dose corticosteroids P. H.
BROWN,G. BLUNDELL*,A. P. GREENINGAND G. K. CROMPTON
Departments of Respiratory Medicine and *Clinical Chemistry, Northern and Western General Hospitals, Edinburgh, U.K.
The frequency of hypothalamo-pituitary-adrenal (HPA) axis suppression in asthmatics taking high dose ( > 1000 pg daily) inhaled corticosteroids is unknown. HPA function was studied in 78 adult asthmatics taking long-term inhaled corticosteroids (median dose 1600/tg, range 1200-2650/tg 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/,tg, n = 36; 2000/zg, n = 26, > 2000 fig, n = 7) and nine budesonide (1200/zg, n = 2; 1600 pg, n = 6; 1800 pg, n = 1). Four patients, all of whom were taking > 2000 pg beclomethasone dipropionate, were taking 200-400 pg 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-~; rise in serum cortisol in response to tetracosactrin < 200 nmol 1-~ and/or achieved cortisol < 500 nmol I- I; urine free cortisol < 80 nmol 24 h - ~. 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°,/o) patients (1500 pg, n = 6 ; 1600pg, n = 1; 2000/zg, n = 7 ; 2400/tg, n = 2 ) . Risk factors identified for this suppression were: (a) previous requirement for long-term systemic corticosteroids (10/26, Z-~=6-1, P 2 0 0 0 p.g BDP (n=7)
Dose of inholed steroid
Fig. 1 9am serum cortisol and response to tetracosactrin i~ asthmatics (n=78) inhaling high dose beclomethasone dipropionate (BDP) or budesonide (BUD). S, Patients using 750-ml spacer devices.
this subgroup analysis as she had required three short courses of prednisolone in the preceding 12 months, the last of these being 1 month prior to tests. She showed no clinical features of cortisol excess, had normal 24-h urine free cortisol excretion and showed normal suppression of serum cortisol in response to an overnight dexamethasone suppression test.
EFFECT OF SHORT COURSES OF PREDNISOLONE
Twenty-four (30.8%) patients had required three or more (maximum six) short courses o f prednisolone in the preceding year. Five of these patients had HPA suppression, three of whom had formerly been taking long-term prednisolone. Of nine patients with a history of long-term and frequent short-term prednisolone therapy, six had normal axis function. Of 14 patients who completed a short course between 2 and 4 weeks prior to assessment, ten had normal axis function. Multiple logistic regression analysis did not show that the number of courses of prednisolone contributed independently to HPA suppression.
EFFECT OF DURATION OF H I G H DOSE INHALED STEROID THERAPY
The 16 patients with H P A suppression had been taking high dose inhaled corticosteroid therapy significantly longer than those with normal function (median 28.5 months vs. 12 months; P
