cosyntropin and Rhinitis--Allergic--Perennial

In adults, morning plasma cortisol levels are twice that of late afternoon and evening values. In children, a delay in the time of onset in peak cortisol levels has been observed in those treated with inhaled corticosteroids. Consequently, the single morning cortisol level has a low sensitivity for detecting adrenal insufficiency in children. It is not clear which test is best for detection of clinically relevant hypothalamic-pituitary-adrenal (HPA) axis suppression in children; 24-hour plasma cortisol is a good test because it measures biologically active, free cortisol levels for the entire day and is noninvasive. 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 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 of 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 of 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. It is unlikely that children are more sensitive to corticosteroids than are adults. There seems to be little point in performing routine monitoring of adrenal function in children who are treated with intranasal corticosteroid treatment.

Topics: Administration, Intranasal; Adrenal Cortex Hormones; Adult; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Clinical Trials as Topic; Cosyntropin; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Insulin; Metyrapone; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

Intranasal mometasone furoate (MF) has been extensively studied in adults and has been found to be safe and effective therapy for the treatment of allergic rhinitis. Several studies have now been conducted on pediatric patients. In all, 990 pediatric patients given mometasone furoate nasal spray (MFNS) have been studied in phase I, II, and III clinical trials. In a dose-ranging study, 5 doses of nasal spray (25, 100, and 200 microg MFNS daily and 168 microg beclomethasone dipropionate daily) were compared with placebo. The 100- and 200-microg daily doses of MFNS were found to be more effective than 168 microg beclomethasone dipropionate or 25 microg MFNS given daily. MFNS (100 microg once daily) was chosen as the appropriate dose. In clinical efficacy and safety trials, MFNS was given to 381 patients 3 to 11 years of age for 4 weeks (357 patients received 100 microg MFNS daily for 6 months) and was found to decrease symptom scores from baseline significantly better than placebo. The long-term safety of MFNS was also studied in 166 patients treated for one year; no significant changes in intraocular pressure were detected. Cosyntropin stimulation showed no decreases in cortisol. In adults, nasal mucosa showed improvement in appearance of epithelium and reduction of inflammatory infiltrates, and there were no signs of nasal atrophy.

Topics: Administration, Intranasal; Anti-Allergic Agents; Anti-Inflammatory Agents; Child; Child, Preschool; Clinical Trials as Topic; Cosyntropin; Dose-Response Relationship, Drug; Humans; Hydrocortisone; Mometasone Furoate; Pregnadienediols; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal; Time Factors

Perennial allergic rhinitis (PAR) affects children at a young age. Current guidelines recommend intranasal corticosteroids as the first-line treatment in patients with moderate-to-severe or persistent disease or in those who have congestion. In this study, the long-term safety and efficacy of mometasone furoate nasal spray (MFNS) were assessed in children with PAR.. In this multicenter, active-controlled, evaluator-blind, 12-month study, 255 children aged 6-11 years with a >or=1-year history of PAR were randomized to receive once-daily MFNS 100 microg (n=166) or the active comparator beclomethasone dipropionate (BDP) 168 microg (n=85). Changes from baseline in overall PAR symptoms and response to treatment were rated at each visit. Cosyntropin stimulation testing, as well as tonometry and slit lamp procedures, were performed. Safety variables were assessed.. A total of 137 subjects in the MFNS group and 68 in the BDP group completed treatment. The mean reductions in physician- and subject-rated overall condition of PAR at week 52 were -42.1% and -39.7%, respectively, for MFNS, compared with -44.0% and -39.0%, respectively, for BDP. A total of 94% and 100% of MFNS and BDP subjects, respectively, reported adverse events (AEs), which were mostly mild or moderate. The most frequently reported treatment-related AEs in both groups were epistaxis, headache, and pharyngitis. Response to cosyntropin was normal and no posterior subcapsular cataracts were observed in either group. Although no significant changes in intraocular pressure were observed with MFNS, one subject receiving BDP demonstrated this effect.. Treatment with MFNS 100 microg once daily for 1 year was well tolerated in children 6-11 years old, with negligible systemic exposure and no evidence of suppression of the hypothalamic-pituitary-adrenal axis or ocular changes.

Topics: Aerosols; Anti-Allergic Agents; Anti-Inflammatory Agents; Beclomethasone; Cerebrospinal Fluid Rhinorrhea; Child; Cosyntropin; Demography; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Mometasone Furoate; Nasal Obstruction; Pregnadienediols; Rhinitis, Allergic, Perennial

Topical corticosteroids are the recommended first-line treatment for all severities of persistent asthma and moderate to severe allergic rhinitis. Potential adrenal suppression resulting from corticosteroid administration necessitates monitoring of children participating in clinical studies. Measurement of pretreatment cortisol concentrations is necessary to assess effects on adrenal function.. Plasma cortisol concentrations are assay dependent; normal reference range values must be obtained for each assay. Our objective is to provide these values for children as determined by HPLC.. Two multicenter, randomized, double-blind, placebo-controlled studies evaluating basal and cosyntropin-stimulated morning plasma cortisol concentrations for patients aged 5 to younger than 12 months with asthma and patients aged 2 to younger than 6 yr with allergic rhinitis using HPLC were conducted.. Main planned outcomes of these studies are reported elsewhere. This manuscript reports plasma cortisol concentration reference range values.. In general, mean basal plasma cortisol concentrations (n = 177) (mean +/- sd, nmol/liter) were similar among the 5 to younger than 9 months, 9 to younger than 12 months, 2 to younger than 3 yr, 3 to younger than 4 yr, 4 to younger than 5 yr, and 5 to younger than 6 yr age groups (218 +/- 149, 281 +/- 144, 257 +/- 105, 231 +/- 83, 298 +/- 118, and 237 +/- 65, respectively) and increased to comparable levels 60 min after cosyntropin stimulation (n = 178; 622 +/- 176, 638 +/- 176, 697 +/- 99, 655 +/- 103, 662 +/- 113, and 610 +/- 68, respectively). However, patients younger than 12 months had wider ranges of basal and stimulated values.. Basal and cosyntropin-stimulated morning plasma cortisol concentrations of children aged 5 to younger than 12 months and 2 to younger than 6 yr were consistently measurable, with the large majority similar among the age groups examined, and comparable with those reported elsewhere for adults.

Topics: Asthma; Child; Child, Preschool; Chromatography, High Pressure Liquid; Cosyntropin; Female; Hormones; Humans; Hydrocortisone; Infant; Male; Rhinitis, Allergic, Perennial; Severity of Illness Index