Systemic effects of intranasal steroids: An endocrinologist’s perspective  David B Allen, MD  Journal of Allergy and Clinical Immunology  Volume 106, Issue 4, Pages S179-S190 (October 2000) DOI: 10.1067/mai.2000.110038

Fig. 1 . The fate of intranasal steroids. The amount of intranasal corticosteroid that reaches the systemic circulation is the sum of nasal and oral bioavailable fractions. The majority of the drug is swallowed, and systemic bioavailability will be determined by the absorption from the gastrointestinal tract and the degree of first-pass hepatic inactivation. The absorption of the fraction that is deposited on the nasal mucosa varies from drug to drug and is influenced by solubility characteristics and other factors. NA, not available. Estimated percentages of systemic bioavailability are from the following sources: IN-FLU,15 IN-BDP,10 IN-BUD,10 IN-MF,17 and IN-FP.10,18 Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 2 . Short-, intermediate-, and long-term tests of the effects of corticosteroids administered to the airways on the HPA axis. Sensitivity for the detection of the systemic presence of INSs or ICSs is greatest with integrated studies of basal HPA axis function (eg, area-under-the-curve cortisol measurements); positive predictive value for risk of adrenal insufficiency is increased by the performance of dynamic tests of adrenal-gland responsiveness (eg, ACTH stimulation [relative predictive values of low-dose vs high-dose ACTH tests have not yet been determined]). AUC , area under the curve; UFC , urinary free cortisol. (Adapted from Allen DB. Limitations of short-term studies in predicting long-term adverse effects of inhaled cortico-steroids. Allergy 1999;54:29-34; © 1999 Munksgaard International Publishers Ltd, Copenhagen, Denmark. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 3 . Short-, intermediate-, and long-term tests of the effects of corticosteroids administered to the airways on growth. Highly sensitive knemometry is a poor predictor of long-term growth, which is more accurately assessed by intermediate-term or long-term whole body stadiometry. (Adapted from Allen DB. Limitations of short-term studies in predicting long-term adverse effects of inhaled corticosteroids. Allergy 1999;54:29-34; © 1999 Munksgaard International Publishers Ltd, Copenhagen, Denmark. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 4 . Mechanisms of growth suppression by corticosteroids (derived from both in vivo and in vitro studies). GHRH, growth hormone releasing hormone; GH, growth hormone; IGF-1, insulin-like growth factor-1. (From Allen DB, Julius JR, Breen TJ, Attie KM. Treatment of glucocorticoid-induced growth suppression with growth hormone. J Clin Endocrinol Metab 1998;83(8):2824-9; © The Endocrine Society. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 5 . Interaction of childhood growth and HPA axes. The commencement of nocturnal pulsatile growth hormone secretion normally coincides with the nadir in plasma cortisol concentrations. Consequently, the administration and absorption of airway corticosteroids at bedtime could theoretically have a disproportionate suppressing influence on growth, compared with early morning dosing. GH , growth hormone. Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 6 . Mean lower-leg growth rates during once-daily treatment with IN-MF 100 μg/d (0.58 mm/wk) or 200 μg/d (0.48 mm/wk), IN-BUD 400 μg/d (0.37 mm/wk), or placebo (0.35 mm/wk). Marked interindividual differences in growth velocity were observed during all 4 treatments. (Adapted from Agertoft L, Pedersen S. Short-term lower leg growth rate in children with rhinitis treated with intranasal mometasone furoate and budesonide. J Allergy Clin Immunol 1999;104:948-52. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 7 . Mean change in standing height from baseline over 1 year of treatment with IN-BDP 168 μg twice daily or placebo. (Adapted from Skoner DP, Rachelefsky GS, Meltzer EO, et al. Detection of growth suppression in children during treatment with intranasal beclomethasone dipropionate. Pediatrics [electronic pages] 2000;105:E23. Reproduced by permission of Pediatrics, © 2000.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 8 . Mean change in standing height from baseline over 1 year of treatment with IN-MF 100 μg once daily or placebo. (Adapted from Schenkel EJ, Skoner DP, Bronsky EA, et al. Absence of growth retardation in children with perennial allergic rhinitis after one year of treatment with mometasone furoate aqueous nasal spray. Pediatrics [electronic pages] 2000;105:E22. Reproduced by permission of Pediatrics, © 2000.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 9 . Mean change in standing height from baseline over 1 year of treatment with inhaled FP 50 μg or 100 μg twice daily or placebo. (Adapted from Allen DB, Bronsky EA, LaForce CF, et al. Growth in asthmatic children treated with fluticasone propionate. J Pediatr 1998;132:472-7. With permission.) Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)

Fig. 10 . Interaction of corticosteroids with bone metabolism, which contributes to the increased risk for osteoporosis. Journal of Allergy and Clinical Immunology 2000 106, S179-S190DOI: (10.1067/mai.2000.110038)