Two-thirds of children on corticosteroids may have hypothalamic-pituitary-adrenal axis dysfunction. In one-third, central function had recovered but adrenal suppression persisted. Predictive factors for HPAS are NS use, BMI, and adherence to ICS and NS.

The effect of inhaled corticosteroids (ICS) on the hypothalamic-pituitary-adrenal axis (HPA) has been regarded as a 'benign physiological response'. A recent survey suggests that adrenal crisis might be more common in asthmatic children on ICS than previously thought. The clinical features of adrenal insufficiency are non-specific and can easily be missed. Accurate biochemical assessment of the axis is therefore mandatory. A review of the literature determined that all basal adrenal function tests, including plasma cortisol profiles, cannot identify which children can respond to stress. There is no evidence to suggests that the degree of the physiological adjustment of the HPA to ICS predicts clinically significant HPA suppression. Only gold standard adrenal function tests can assess the integrity of the whole axis. Of the two available tests, the correctly performed overnight metyrapone test (with ACTH levels) is safe and better by far. The use of cortisol profiles should only be used to demonstrate differences in systemic activity of various ICS and delivery devices. Regulatory bodies should insist on trials that evaluate the HPA with a gold standard adrenal function test before it is declared safe and allowed to be marketed. A re-analysis of studies that have utilized gold standard adrenal function tests only might identify the lowest safe dose and duration of ICS.

The evidence for hypothalamic-pituitary-adrenal axis (HPA) suppression by inhaled corticosteroids (ICS) was found to be conflicting. Reviewers have not distinguished between gold standard and basal adrenal function tests. The utility of the latter is limited by physiological and pathological variability as well as by methodological concerns. The risk of HPA suppression in asthmatic children and adolescents treated with ICS, as determined by gold standard adrenal function tests, needs to be established. A systematic review of the literature from January 1973 to July 2005 was performed. The Medline and Cochrane databases were searched, the reference lists of retrieved articles were inspected and pharmaceutical companies were approached. Randomized-controlled trials, cohort and case-control studies designed to detect HPA suppression caused by ICS, diagnosed by the insulin tolerance test (ITT) or the metyrapone test, performed on asthmatics of all ages not on oral steroids, were included and assessed for methodological quality. Of the 22 identified studies only four met the criteria for inclusion. All of these were published before 1988 and only one was methodologically sound. The cohort study showed that the baseline risk for HPA suppression is 0% while the absolute risk is 100% in asthmatic children treated with a beclomethasone dipropionate metered dose inhaler at a dose of 250-600 mug/m(2)/day for 6-42 months. As suggested by other observations these results could be generalized to other ICS. They may be of clinical significance especially if children are subjected to stress. Further research is needed to establish the cumulative dose for all ICS at which HPA suppression will be precipitated. Guidelines for future trials are suggested.

BackgroundDespite changes in WHO guidelines, stavudine is still used extensively for treatment of pediatric HIV in the developing world. Lipoatrophy in sub-Saharan African children can be stigmatizing and have far-reaching consequences. The severity and extent of lipoatrophy in pre-pubertal children living in sub-Saharan Africa is unknown.MethodsIn this cross-sectional study, children who were 3-12 years old, on antiretroviral therapy and pre-pubertal were recruited from a Family HIV Clinic in South Africa. Lipoatrophy was identified and graded by consensus between two HIV pediatricians using a standardized grading scale. A professional dietician performed formal dietary assessment and anthropometric measurements of trunk and limb fat. Previous antiretroviral exposures were recorded. In a Dual-Energy X-ray Absorbtiometry (DXA) substudy body composition was determined in 42 participants.ResultsAmong 100 recruits, the prevalence of visually obvious lipoatrophy was 36% (95% CI: 27%–45%). Anthropometry and DXA measurements corroborated the clinical diagnosis of lipoatrophy: Both confirmed significant, substantial extremity fat loss in children with visually obvious lipoatrophy, when adjusted for age and sex. Adjusted odds ratio for developing lipoatrophy was 1.9 (95% CI: 1.3 - 2.9) for each additional year of accumulated exposure to standard dose stavudine. Cumulative time on standard dose stavudine was significantly associated with reductions in biceps and triceps skin-fold thickness (p=0.008).ConclusionsThe prevalence of visually obvious lipoatrophy in pre-pubertal South African children on antiretroviral therapy is high. The amount of stavudine that children are exposed to needs review. Resources are needed to enable low-and-middle-income countries to provide suitable pediatric-formulated alternatives to stavudine-based pediatric regimens. The standard stavudine dose for children may need to be reduced. Diagnosis of lipoatrophy at an early stage is important to allow timeous antiretroviral switching to arrest progression and avoid stigmatization. Diagnosis using visual grading requires training and experience, and DXA and comprehensive anthropometry are not commonly available. A simple objective screening tool is needed to identify early lipoatrophy in resource-limited settings where specialized skills and equipment are not available.

Background: Hypothalamic pituitary adrenal axis suppression (HPAS) when treating asthmatic children with inhaled corticosteroids (ICS) is thought to be rare. Objective: To determine the prevalence of HPAS in asthmatic children treated with ICS and nasal steroids (NS). Methods: Twenty-six asthmatic children were recruited. Clinical features of HPAS, height, weight, height and weight velocity, steroid dose, adherence, symptom control and lung functions were documented. Metyrapone test was performed if the serum cortisol was > 83 nmol/L ( > 3 µ g/dL). Results: No child had a serum cortisol < 83 nmol/L ( < 3 µ g/dL). Prevalence of HPAS was 35 (CI = 17 % -56 % ). Daily NS dose/ m 2 and cumulative NS dose/m 2 were signifi cantly (p = 0.03) inversely correlated with the post-metyrapone ACTH (r = -0.42 for both). Current ICS dose was not associated with the post-metyrapone ACTH (r = 0). There was a weak correlation with the daily ICS dose/m 2 (r = -0.12) and cumulative ICS dose/m 2 (r = -0.26).