The effect of an inhaled steroid on the hypothalamic‐pituitary‐adrenal axis‐which tests should be used?

Holt, Peter R.; Lowndes, D. W.; Smithies, Elizabeth; Dixon, Gavin

doi:10.1111/j.1365-2222.1990.tb02659.x

Cited by 45 publications

(15 citation statements)

References 8 publications

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“…The basal cortisol level does not adequately predict the response to ACTH or the insulin-induced hypoglycemia test [9] . Additionally, the 24-hour urinary free cortisol may decrease without any change in morning plasma cortisol level [10] . Furthermore, the measurement of a single plasma level of ACTH at 08: 00 h is even more variable and of less value than a single measurement of plasma cortisol at the same time, because ACTH release is pulsatile throughout the night [11] .…”

Section: Basal Adrenal Function Testsmentioning

confidence: 99%

Intranasal Corticosteroids and Adrenal Suppression

Bruni¹,

Luca²,

Venturoli³

et al. 2009

Neuroimmunomodulation

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Allergic rhinitis is a common condition that frequently coexists with asthma and atopic dermatitis. It is commonly treated with intranasal corticosteroids which may increase the potential inception of side effects of the same type of drugs used for the treatment of other allergic diseases. A method to assess the systemic effect of corticosteroids is the evaluation of their effect on the hypothalamic-pituitary-adrenal (HPA) axis. However, it is not clear which test is best for detection of clinically relevant HPA axis suppression in children Morning plasma cortisol levels are twice that of late afternoon and evening values and a delay in the time of onset in peak cortisol levels has been observed in children treated with inhaled corticosteroids. Single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. 24-Hour plasma cortisol is a good test because it is a non-invasive measure of the biologically active free cortisol levels for the entire day. For research purposes, the 24-hour integrated concentration plasma cortisol test is preferred. Studies that have looked at HPA axis suppression with intranasal corticosteroids indicate that overall, intranasal corticosteroids have a minimal effect on the HPA axis. A review of the literature reveals one study in which there was a decreased output of urinary cortisol during treatment with either budesonide or fluticasone propionate in adults. Other studies with fluticasone propionate or budesonide have shown no effect on the HPA axis in children. Beclomethasone dipropionate was shown to affect urinary cortisol output in one study on healthy volunteers. However, in a long-term study in children, no effect on the HPA axis was found. Mometasone furoate has been extensively studied in more than 20 trials of adults and children. No effects on the HPA axis were detected in either children or adults. Fluticasone furoate nasal spray was not associated with HPA axis suppression. It is unlikely that children are more sensitive to corticosteroids than adults. There is no reason to perform routine monitoring of adrenal function in children who are treated with intranasal corticosteroid unless those drugs are used concomitantly with inhaled corticosteroids and/or steroid ointments for the possible concomitant presence of asthma and/or atopic dermatitis.

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Section: Basal Adrenal Function Testsmentioning

confidence: 99%

Intranasal Corticosteroids and Adrenal Suppression

Bruni¹,

Luca²,

Venturoli³

et al. 2009

Neuroimmunomodulation

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“…Stimulation tests have also been used to detect the effect of inhaled steroids on the hypothalamicpituitary-adrenal axis [29]. After a meta-analysis including 27 studies performed during 1966-1998, it was concluded that using w1.5 mg inhaled steroid?day -1 resulted in a marked adrenal suppression [30].…”

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“…Although practical experience throughout the past 30 yrs has proved that inhaled steroids are safe drugs for most patients, it has also been shown that in higher doses, a systemic effect is detectable by demonstrating an early morning dip in serum cortisol when measuring 24-h integrated and fractionated (overnight, 08.00 h, daytime) serum cortisol levels and urinary cortisol/creatinine excretion [28,29]. Stimulation tests have also been used to detect the effect of inhaled steroids on the hypothalamicpituitary-adrenal axis [29].…”

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Inhaled steroids in children: adrenal suppression and growth impairment

Carlsen¹,

Gerritsen²

2002

Eur Respir J

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Inhaled steroids have been used for many years. The first report of their beneficial use in asthmatic children was published almost 30 yrs ago [1]. With increasing knowledge of the side-effects of systemically administered steroids, there has been a steady increase in the use of inhaled steroids, and they are presently considered to be the most important treatment for asthma. Inhaled steroids are the cornerstone of all guidelines on asthma treatment [2][3][4]. They reduce symptoms in children with asthma [5], improve quality of life in asthmatic children and their families [6], decrease patients9 and their parents9 absence from school/work [7], reduce airway inflammation [8], and improve lung function [9], bronchial responsiveness [10] and exercise-induced asthma [11,12]. The sale and use of inhaled steroids has markedly increased in Nordic countries since the late 1980s, which has probably had an impact upon the admission rate of childhood asthma in these countries. In older children, the admission [13] and particularly readmission [14] rates for acute asthma have decreased in these countries. The use of inhaled steroids has thus had a major impact upon daily life and the "mastering" of asthma in asthmatic children.Despite the beneficial effects of inhaled steroids in childhood asthma, general agreement as to how early to start treatment has not been reached. This is mostly due to the general fear of the side-effects of inhaled steroids, but also because of an awareness of the possible effects upon lung growth in young children, as has been reported by the use of systemic steroids in animal experiments [15].The local side-effects of inhaled steroids on skin, the mucous membranes of the respiratory tract, and the oropharyngeal area are also well known, but have received much less attention than the systemic sideeffects. The local side-effects consist of perioral dermatitis, oral candidiasis, hoarseness, dysphonia, cough during inhalation and a feeling of thirst [16].However, systemic side-effects, including suppression of the hypothalamic-hypophyseal-adrenal axis [17][18][19] Posterior subcapsular cataracts have been described as developing after systemic steroids have been used and, in three patients, on inhaled beclomethasone dipropionate with occasional short courses of systemic steroids over several years [25]. However, systematic studies have not indicated an increased risk of cataracts with the use of inhaled steroids [26,27].Although practical experience throughout the past 30 yrs has proved that inhaled steroids are safe drugs for most patients, it has also been shown that in higher doses, a systemic effect is detectable by demonstrating an early morning dip in serum cortisol when measuring 24-h integrated and fractionated (overnight, 08.00 h, daytime) serum cortisol levels and urinary cortisol/creatinine excretion [28,29]. Stimulation tests have also been used to detect the effect of inhaled steroids on the hypothalamicpituitary-adrenal axis [29]. After a meta-analysis including 27 studies performed dur...

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“…Previous studies of the systemic effects of ICS have employed very insensitive techniques, such as the measurement of morning cortisol, and have failed to show any significant effect even at moderately high doses [4]. However, integrated overnight plasma cortisol concentrations or urinary-free cortisol have been suggested as more sensitive tests of reduced hypothalamic pituitary adrenal axis function and as being superior to stimulation tests [5,6].In a cross-sectional study of plasma cortisol measured every 20 min during sleep in 19 asthmatic children, we demonstrated that there was a dose-related effect of inhaled beclomethasone dipropionate (BDP) on overnight cortisol production, despite the fact that there was no difference in the height of the morning peak of cortisol [7]. As this study did not account for the effect of asthma itself, we conducted a subsequent prospective cross-over study of integrated plasma cortisol concentrations and urinary-free cortisol in 12 children commencing ICS for the first time.…”

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confidence: 99%

mentioning

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One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

Nikolaizik¹,

Preece²,

Warner³

1997

Eur Respir J

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To weigh the benefits and risks of long-term treatment, 12 children with moderately severe asthma were assessed in a follow-up study on budesonide 200 µg b.i.d.After 1 yr, the nocturnal cortisol production was significantly reduced by 19%, but no greater compared to 2 and 4 weeks of treatment. Growth and growth hormone levels were normal. Lung function tests were significantly better, not only versus baseline values but also versus 2 and 4 weeks of treatment.We conclude that systemic effects of inhaled corticosteroids in conventionally low doses do not accumulate with length of treatment, whilst lung function parameters will continue to improve. Therefore, inhaled corticosteroids once started in asthmatic children not controlled on other medications should be continued, but their use should be carefully considered and the minimal dose required to control the asthma employed. Eur Respir J 1997; 10: 2596-2601 Inhaled corticosteroids (ICS) are the principal drugs used in the management of moderate-to-severe childhood as well as adult asthma [1,2]. However, awareness of the possible systemic effects of ICS in children has been a source of concern, particularly when they are used in high doses [3]. Previous studies of the systemic effects of ICS have employed very insensitive techniques, such as the measurement of morning cortisol, and have failed to show any significant effect even at moderately high doses [4]. However, integrated overnight plasma cortisol concentrations or urinary-free cortisol have been suggested as more sensitive tests of reduced hypothalamic pituitary adrenal axis function and as being superior to stimulation tests [5,6].In a cross-sectional study of plasma cortisol measured every 20 min during sleep in 19 asthmatic children, we demonstrated that there was a dose-related effect of inhaled beclomethasone dipropionate (BDP) on overnight cortisol production, despite the fact that there was no difference in the height of the morning peak of cortisol [7]. As this study did not account for the effect of asthma itself, we conducted a subsequent prospective cross-over study of integrated plasma cortisol concentrations and urinary-free cortisol in 12 children commencing ICS for the first time. Both BDP or budesonide (BUD), at a dose of 200 µg b.i.d. for 2 weeks in randomized order, caused identical significant suppressive effects on overnight cortisol production [8]. We found similar suppression in a controlled study administering either a single dose of 400 µg of BUD in the evening to healthy adults, or administering 400 µg twice daily for 2 weeks [9].The above studies were of very short duration and there remained a concern that there might be a cumulative effect of continuing ICS over longer periods. Indeed, nocturnal serum cortisol production was reduced by 27% after 2 weeks and 35% after 4 weeks of treatment in the paediatric study, with similar apparent increases in effects in suppression of urinary-free cortisol (33 and 48%, respectively). We therefore, repeated the studies on the same patients af...

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The effect of an inhaled steroid on the hypothalamic‐pituitary‐adrenal axis‐which tests should be used?

Cited by 45 publications

References 8 publications

Intranasal Corticosteroids and Adrenal Suppression

Intranasal Corticosteroids and Adrenal Suppression

Inhaled steroids in children: adrenal suppression and growth impairment

One year follow-up study of endocrine and lung function of asthmatic children on inhaled budesonide

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