Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone

Paton, James Y.; Jardine, E; McNeill, E; Beaton, Stephen; Galloway, Peter; Young, David; Donaldson, M D C

doi:10.1136/adc.2005.087247

Cited by 74 publications

(56 citation statements)

References 30 publications

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“…None of the studies measured the final adult height attained, despite the fact that this is of most interest to children and parents. Only 14 studies measured the effect of ICS, when administered for longer than one year, on hypothalamo-pituitaryadrenal function, despite the serious and potentially fatal consequences of this type of adverse reaction [37]. We suggest that serious systemic side effects should be monitored in all clinical trials of ICS in children with asthma, so that both the benefits and risks of these drugs can be appropriately evaluated.…”

Section: Discussionmentioning

confidence: 99%

Outcomes in Clinical Trials of Inhaled Corticosteroids for Children with Asthma Are Narrowly Focussed on Short Term Disease Activity.

Sinha¹,

Williamson²,

Smyth³

2009

C61. Pediatric Asthma

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Background: Little work has been done to determine which outcomes should be measured in randomised controlled trials (RCTs) in children with asthma. Drug regulatory authorities require that short term disease activity is measured, but other outcome domains are not mandatory for licensing and marketing purposes. We aimed to identify whether any domains were underrepresented in RCTs of regular therapies for children with asthma over a 20 year period, and to examine what consistency there was between RCTs in the outcomes used to assess the domains.

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Section: Discussionmentioning

confidence: 99%

Outcomes in Clinical Trials of Inhaled Corticosteroids for Children with Asthma Are Narrowly Focussed on Short Term Disease Activity.

Sinha¹,

Williamson²,

Smyth³

2009

C61. Pediatric Asthma

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“…Patients receiving systemic glucocorticoids or high-dose inhaled glucocorticoids were also excluded. High-dose inhaled glucocorticoids were defined as a dose of fluticasone propionate R400 mg daily or an equivalent dose of budesonide or beclomethasone (R800 mg daily) (13). Patients with peak cortisol values between 400 and 500 nmol/l (14.4-18 mg/dl) were included in the analysis, as reference values in this range have been reported previously as normal in healthy children and adolescents (7,8).…”

Section: Subjectsmentioning

confidence: 99%

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

O’Grady

Hensey

Fallon

et al. 2013

European Journal of Endocrinology

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Objective: Based on adult data, a peak cortisol response R500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age. Design: The present study was a retrospective cohort study. Methods: Retrospective analysis of children and adolescents aged %18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic-pituitary-adrenal axis impairment (peak cortisol value !400 nmol/l) or using systemic glucocorticoids were excluded. Results: Two hundred and twenty-three tests were analysed. Peak cortisol responses R500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (rZK0.15, PZ0.03). A peak cortisol response !500 nmol/l was significantly less common in patients aged !12 years (9/97 (9%) vs 31/126 (25%); PZ0.004). In children aged !12 years, the median (5th-95th centiles) peak cortisol values were 610 (480-806) nmol/l compared with 574 (442-789) nmol/l in children aged R12 years (P!0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (PZ0.0004)). Conclusions: Use of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.

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“…A flat adrenal response in association with fluticasone propionate in 2.8% of children tested (LDST) receiving 1 1,000 g/day was also reported, whereas impaired responses were seen in 39.6% of these patients [55] .…”

Section: Effects Of Ics On Hpa Axis In Asthmatic Childrenmentioning

confidence: 99%

Endocrine-Immune Interactions in Adrenal Function of Asthmatic Children on Inhaled Corticosteroids

Priftis

Papadimitriou²,

Anthracopoulos

et al. 2009

Neuroimmunomodulation

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The present review highlights adrenal function in the context of endocrine-immune interactions and hypothalamic-pituitary-adrenal (HPA) axis activity in asthmatic children on long-term treatment with inhaled corticosteroids (ICS). Activation of the HPA axis by specific cytokines increases the release of cortisol, which in turn feeds back and suppresses the immune reaction. Reduced responsiveness of the HPA axis in patients with various chronic allergic inflammatory disorders and a blunted HPA axis response of poorly controlled asthmatics before long-term treatment with ICS have been reported. It appears that pro- and anti-inflammatory cytokines may be involved in the attenuation of cortisol and ACTH responses to stress in these patients. ICS as anti-inflammatory agents may have favorable effects in asthmatics with baseline subnormal adrenal responses, thus improving adrenal function during successful long-term treatment; on the other hand, few patients on conventional doses may experience further deterioration of adrenal function, a phenomenon that most likely is genetically determined. When ICS are administered at high doses, secondary adrenal insufficiency due to the excessive exogenous corticosteroid certainly may become manifest.

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Adrenal responses to low dose synthetic ACTH (Synacthen) in children receiving high dose inhaled fluticasone

Cited by 74 publications

References 30 publications

Outcomes in Clinical Trials of Inhaled Corticosteroids for Children with Asthma Are Narrowly Focussed on Short Term Disease Activity.

Outcomes in Clinical Trials of Inhaled Corticosteroids for Children with Asthma Are Narrowly Focussed on Short Term Disease Activity.

Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children

Endocrine-Immune Interactions in Adrenal Function of Asthmatic Children on Inhaled Corticosteroids

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