Hypothalamic‐pituitary‐adrenal axis suppression in asthmatic children on inhaled corticosteroids: Part 1. Which test should be used?

Abstract

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.

Inhaled Corticosteroids in Lung Diseases

“…Several methods have been used to measure HPA axis function with 24-hour serum area-under-the-curve cortisol, low-dose adrenocorticotropin stimulation, and 24-hour and overnight urinary free cortisol being the most sensitive indicators of exogenous corticosteroid exposure (5,66). The standard test to evaluate the full integrity of the HPA axis is insulin-hypoglycemic stimulation, but standard-dose adrenocorticotropin stimulation has been used for regulatory purposes (66).…”

“…The standard test to evaluate the full integrity of the HPA axis is insulin-hypoglycemic stimulation, but standard-dose adrenocorticotropin stimulation has been used for regulatory purposes (66). Although 24-hour urinary cortisol excretion has been approved to compare relative systemic activity from the ICSs, the degree of suppression does not correlate with risk of adrenal insufficiency (58,66). Patients exposed to high doses of ICSs (based on guidelines; Table 2) should have their HPA axis monitored (65).…”

Cortisol basal em asmáticos em uso de duas diferentes doses de propionato de fluticasona

“…Furthermore, when ACTH drops, cortisol also decreases rapidly. 12 There is a report of adrenal suppression after 5 weeks' fluticasone use. 15 With relation to selection and sampling, the study con- …”

Retirada da corticoterapia: recomendações para a prática clínica

“…14 The hyperpigmentation of skin and mucosas that is typical of Addison's disease is not present, since pituitary secretion of ACTH is inhibited. 1,14,28 Some patients may exhibit hypoglycemia. Hyponatremia and hyperkalemia are uncommon because ACTH suppression has a minimal effect on aldosterone secretion.…”

“…42 Determination of free cortisol in 24-hour urine is not indicated for assessing lack of HPA axis function since less than 1% of free cortisol is excreted in urine. 28 Therefore, this test is more used to assess hypercortisolism, which is a situation in which transcortin saturation occurs, thereby making increased excretion of free cortisol in urine possible.…”