PC NG

Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is one of the most serious adverse effects of corticosteroids therapy. As high dose antenatal and postnatal dexamethasone are of proven value and now frequently prescribed for lessening the severity of respiratory distress syndrome and for the treatment of bronchopulmonary dysplasia in very low birth weight (VLBW) infants, an understanding of its influence on their HPA axis is important. Since there is evidence to suggest that a single measurement of serum cortisol does not permit reliable assessment of pituitary-adrenal function because of episodic secretion, a reliable and reproducible endocrine test is essential for identifying infants with diminished endocrine reserve and impaired endogenous hormone production.

In a recent study, we have demonstrated that the human corticotropin releasing hormone (hCRH) stimulation test is safe, reproducible, and capable of producing a consistent pituitary-adrenal response in preterm, VLBW infants similar to those seen in older children and adults. Furthermore, our findings suggest that both the pituitary and adrenal glands are functionally responsive at these very early gestations.

Using the same test, we had also shown that severe pituitary-adrenal suppression occurred immediately after a 3 week course of systemic dexamethasone. This was, however, followed by substantial recovery in endocrine function one month after stopping steroid treatment. Although both the pituitary and adrenal glands were capable of mounting a biochemically adequate response to exogenous hCRH stimulation at this stage, the sequence of improvement appeared to be earlier with the pituitary center. Steroid replacement therapy might be desirable at time of stress in the immediate posttreatment period, but would seem unnecessary one month after discontinuation of dexamethasone therapy.

In the most recent study, we also found that a 2-week course of inhaled corticosteroids (fluticasone propionate) caused moderately severe pituitary-adrenal suppression in VLBW infants. The systemic bioactivity is likely to be associated with pulmonary vascular absorption which effectively circumvents the hepatic first-pass metabolism. Until the question of safety could be adequately addressed, inhaled corticosteroids should be used with caution in preterm infants.