Axis Suppression In Children Research Articles

The Prevalence of Hypothalamic-Pituitary-Adrenal Axis Suppression in Children with Persistent Asthma

Background: Hypothalamic-pituitary-adrenal (HPA) axis suppression is the most important systemic side effect associated with inhaled corticosteroids (ICS) therapy. Objectives: To evaluate the prevalence and determinants of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on ICSs. Methods: A total of 92 children aged 6 to 18 years, diagnosed with persistent asthma, and receiving regular ICS therapy for a minimum of 3 months, without any systemic steroid therapy within the last 3 months, were enrolled in the study. Clinical and demographic variables were recorded. HPA axis suppression was measured by morning cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation test. Results: Of 92 enrolled patients, 51 (55.4%) were male. The mean age was 10.1 ± 2.6 years. HPA axis suppression was observed in two (2.1%) patients. The body mass index (BMI) values were significantly lower in the HPA axis suppression group compared to the other enrollees. No relationship was observed between the HPA axis suppression and the ICS dose, duration of therapy or co-administration of long-acting beta-agonists or nasal steroids. Conclusions: In our study, the prevalence of HPA axis suppression was 2.1%. Children with persistent asthma who has been treated with regular ICS should be screened for HPA axis suppression.

High prevalence of HPA axis suppression in children taking corticosteroids

High prevalence of HPA axis suppression in children taking corticosteroids

Prevalence of Hypothalamic-Pituitary-Adrenal Axis Suppression in Children Treated for Asthma with Inhaled Corticosteroid

Prevalence of Hypothalamic-Pituitary-Adrenal Axis Suppression in Children Treated for Asthma with Inhaled Corticosteroid

Prevalence of hypothalamic-pituitary-adrenal axis suppression in children treated for asthma with inhaled corticosteroid.

To determine the prevalence of hypothalamic-pituitary-adrenal (HPA) axis suppression in asthmatic children on inhaled corticosteroids (ICS). Clinical and demographic variables were recorded on preconstructed, standardized forms. HPA axis suppression was measured by morning serum cortisol levels and confirmed by low-dose adrenocorticotropic hormone stimulation testing. In total, 214 children participated. Twenty children (9.3%, 95% CI 5.3% to 13.4%) had HPA axis suppression. Odds of HPA axis suppression increased with ICS dose (OR 1.005, 95% CI 1.003 to 1.009, P<0.001). All children with HPA axis suppression were on a medium or lower dose of ICS for their age (200 μg/day to 500 μg/day). HPA axis suppression was not predicted by drug type, dose duration, concomitant use of long-acting beta-agonist or nasal steroid, or clinical features. Laboratory evidence of HPA axis suppression exists in children taking ICS for asthma. Children should be regularly screened for the presence of HPA axis suppression when treated with high-dose ICS (>500 μg/day). Consideration should be given to screening children on medium-dose ICS.

Intranasal Corticosteroids and Adrenal Suppression

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.

Assessment of Adrenal Suppression in Children With Asthma Treated With Inhaled Corticosteroids: Use of Dehydroepiandrosterone Sulfate as a Screening Test

Dorsey MJ, Cohen LE, Phipatanakul W, Denufrio D, Schneider LC. Ann Allergy Asthma Immunol. 2006;97:182–186 PURPOSE OF THE STUDY. To evaluate dehydroepiandrosterone sulfate (DHEA-S), a corticotropin-dependent adrenal androgen precursor, as a possible marker for adrenal function and hypothalamic-pituitary-adrenal axis suppression in children treated with inhaled corticosteroids (ICSs) compared with low-dose (0.5 μg/m2 up to 1.0 μg) and standard-dose (250 μg) cosyntropin-stimulation testing. STUDY POPULATION. Twenty-two patients with moderate-to-severe–persistent asthma receiving a medium-to-high dose of ICSs for at least 6 months were enrolled (definition of median-to-high dose of ICS: budesonide &amp;gt;400 μg/day or fluticasone &amp;gt;176 μg/day for children &amp;lt;6 years old or &amp;gt;200 μg/day for those ≥6 years). Patients had received no more than 2 courses of systemic corticosteroid exposure of &amp;lt;10 days’ duration in the previous 6 months and no systemic corticosteroid in the 1 month before enrollment. The average age of the patients was 8.6 years (range: 2–12 years). METHODS. After a 12-hour fast, morning cortisol, corticotropin, DHEA-S, and fasting blood sugar levels were measured. Cortisol was measured after the stimulation tests. A cortisol level of ≤18 μg/dL was considered abnormal (adrenal suppression). RESULTS. Of 22 patients, 13 (59%) had an abnormal response to low-dose cosyntropin. One patient had an abnormal standard-dose cosyntropin test result. The normal and abnormal low-dose cosyntropin responders did not differ in age, height, BMI, predicted forced expiratory volume in 1 second, or morning cortisol, corticotropin, or fasting blood sugar levels. There was no difference between normal and abnormal low-dose cosyntropin responders in relation to type of ICS (fluticasone, fluticasone-salmeterol, or budesonide) or dose. DHEA-S levels were significantly lower in abnormal low-dose cosyntropin responders compared with normal responders (31 vs 91 μg/dL; P = .004). Age- and gender-specific mean DHEA-S z scores were significantly lower in abnormal low-dose cosyntropin responders. Receiver-operating-characteristic (ROC) curves for DHEA-S z scores were calculated to obtain optimal cutoff values for DHEA-S. The ROC curve for DHEA-S z scores reached 100% sensitivity with a DHEA-S z score of less than −1.5966 and 100% specificity with a DHEA-S z score &amp;gt;0.0225. CONCLUSIONS. Fifty-nine percent of the children on a medium-to-high dose of ICS had biochemical evidence of adrenal suppression according to the low-dose cosyntropin-stimulation test. Low DHEA-S levels can be used as a screening test to identify children who need more formal testing of the hypothalamic-pituitary-adrenal axis. The half-life of DHEA-S (10–20 hours) is substantially longer than that of cortisol (&amp;lt;2 hour) and, therefore, has less diurnal variation or fluctuating concentration depending on exogenous stress and time of day. REVIEWER COMMENTS. The cosyntropin-stimulation test is cumbersome, labor intensive, and not practical as a screening test, so the DHEA-S test may be more useful. The number of patients on a moderate dose of ICS found to have biochemical adrenal suppression by low-dose cosyntropin tests (59%) is higher than seen in most other studies. The authors speculated that the higher rates of adrenal suppression may be associated with “real-world” ICS use versus study-protocol use. The clinical significance of this biochemical suppression is not clear.

Effects of intranasal corticosteroids on the hypothalamic-pituitary-adrenal axis in children

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 insuffiency 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 corticoster-oid treatment. (J Allergy Clin Immunol 2001;108:S32-9.)