Suppression and recovery of the neonatal hypothalamic-pituitary-adrenal axis after prolonged dexamethasone therapy

Objective: To evaluate the duration and level of hypothalamic-pituitary-adrenal (HPA) axis suppression in premature infants treated with a prolonged course of glucocorticoids for chronic lung disease. Study design: We evaluated HPA axis function in nine very low birth weight (VLBW) infants before and 48 hours after a prolonged (14 to 42 days) dexamethasone (Dex) course. Seven of these infants underwent serial testing in the Clinical Research Center to evaluate the time course of HPA axis recovery. Adrenal function was assessed directly with synthetic adrenocorticotropic hormone (ACTH) stimulation, pituitary function with ovine corticotrophin releasing hormone (oCRH) stimulation, and combined axis function with 3-hour metyrapone testing. Results: Baseline cortisol values were higher before Dex therapy (18.6 +/- 3.9 mu g/dl; mean +/- SEM) than after (5.77 +/- 1.45 mu g/dl; p < 0.01), as were ACTH-stimulated cortisol levels (24.8 +/- 1.7 mu g/dl vs 12.0 +/- 2.2 mu g/dl; p < 0.001). ACTH response to oCRH decreased after Dex treatment (22.8 +/- 7.6 rho g/ml vs 11.5 +/- rho g/ml), but this was not statistically significant (p = 0.18). 11-Deoxycortisol (11-DOC) response to metyrapone dropped from 11.1 +/- 0.5 mu g/dl to 4.7 +/- 1.0 mu g/dl after Dex therapy (p < 0.0001). Longitudinal testing reveals that adrenal suppression may be short-lived, while recovery of higher centers is more delayed. Conclusions: Basal cortisol levels may be used as a screening test, but if the level is less than 15 mu g/dl, more definitive testing should be performed. The sluggish recovery of higher HPA axis centers is most reliably evaluated by using 11-DOC response to a single dose of metyrapone in VLBW infants after prolonged Dex therapy.