Effects of Glucocorticoids on the Hypothalamic-Pituitary-Adrenal Axis in Children and Adults
Section snippets
Pharmacology
Glucocorticosteroids exert their powerful anti-inflammatory actions by way of glucocorticoid receptors in the cytoplasm. The interaction between the receptor complex and the corticosteroid response element results in stimulation or inhibition of corticosteroid-responsive target genes [6]. Glucocorticoid receptors are located in many tissues and regulate many metabolic functions. The response in individuals receiving the same dose of corticosteroids may vary significantly. Genetic polymorphisms
Methods of hypothalamo-pituitary-adrenal assessment
HPA axis suppression is an accepted quantifiable indicator of the potential risk for adverse effects related to systemic corticosteroids [10]. The ideal test for diagnosing HPA dysfunction needs to be safe, reliable, and easy to perform. There are many tests that assess HPA function, but there is continuing controversy over which is the best. Methods for assessing HPA axis activity are notoriously susceptible to inaccuracies and difficulty in interpretation. Because of diurnal periodicity of
Inhaled corticosteroids
Compared with oral corticosteroids, all ICS have an improved safety profile [28]. The following ICS are approved for use in children in the United States: beclomethasone dipropionate (BDP), budesonide (BUD), flunisolide (FLU), fluticasone propionate (FP), and triamcinolone acetonide (TA). Differences in the safety profiles of these agents are difficult to ascertain and few studies aim to provide a direct comparison in the risk/benefit ratios of each preparation. There are many confounding
Topical nasal corticosteroids
Topical nasal corticosteroids are widely used for the treatment of rhinosinusitis and nasal polyposis in children and adults. Intranasal corticosteroids currently available for treatment include BUD, FLU, FP, MF, and TA. The aims of topical therapy in this condition are to maximize therapeutic benefits of corticosteroids at the site of disease while minimizing adverse effects, such as suppression of the HPA axis. Systemic absorption does occur, however, either directly through the nasal mucosa
Recommendations for children
An editorial in 2002 warned pediatricians to be alert to the clinical features of hypoadrenalism in children taking ICS [77]. At times of metabolic stress, symptoms may indicate an impending adrenal crisis. Such a crisis may present as acute hypoglycemia, altered consciousness, hemodynamic collapse, coma, convulsions, or even death. Symptoms suggestive of adrenal insufficiency are nonspecific and include lethargy, weight loss, anorexia, hyperpigmentation, vomiting, hypoglycemia, and electrolyte
Clinical significance of hypothalamo-pituitary-adrenal axis suppression
Whether ICS are used orally, by the inhaled route, or the intranasal route, the unwanted adverse effects on the HPA axis are mainly caused by the systemic bioavailable portion of the dose. Although it is established that systemic absorption occurs from the use of inhaled and intranasal corticosteroids, the level at which clinically relevant adverse effects appear remains controversial.
Furthermore, even in the absence of abnormal growth or cushingoid features, children receiving high-dose
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Lack of effect on adult and adolescent hypothalamic-pituitary-adrenal axis function with use of fluticasone furoate nasal spray
2008, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :Thus, it is especially important to determine the effect of treatment with an intranasal corticosteroid on the HPA axis in pediatric patients. Trials with older intranasal corticosteroids (budesonide, beclomethasone dipropionate, and triamcinolone acetonide) that have lower first-pass metabolism, higher bioavailability,27,28 and higher free drug concentrations than fluticasone furoate have not shown any effect on urinary or plasma cortisol levels or any clinically significant suppression of the HPA axis.20,29,30 Therefore, although patients younger than 12 years were not included in the present trial, it is anticipated that fluticasone furoate, with its very low systemic bioavailability, will also have an excellent tolerability profile relative to these older agents.
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