SUPPRESSION AND RECOVERY OF THE NEONATAL HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AFTER PROLONGED DEXAMETHASONE THERAPY

Objective: To evaluate the duration and level of hypothalamic-pituitar y-adrenal (HPA) axis suppression in premature infants treated with a p rolonged course of glucocorticoids for chronic lung disease. Study des ign: We evaluated HPA axis function in nine very low birth weight (VLB W) infants before and 48 hours after a prolonged (14 to 42 days) dexam ethasone (Dex) course. Seven of these infants underwent serial testing in the Clinical Research Center to evaluate the time course of HPA ax is recovery. Adrenal function was assessed directly with synthetic adr enocorticotropic hormone (ACTH) stimulation, pituitary function with o vine corticotrophin releasing hormone (oCRH) stimulation, and combined axis function with 3-hour metyrapone testing. Results: Baseline corti sol 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-st imulated 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 statistical ly significant (p = 0.18). 11-Deoxycortisol (11-DOC) response to metyr apone dropped from 11.1 +/- 0.5 mu g/dl to 4.7 +/- 1.0 mu g/dl after D ex therapy (p < 0.0001). Longitudinal testing reveals that adrenal sup pression 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 testi ng should be performed. The sluggish recovery of higher HPA axis cente rs is most reliably evaluated by using 11-DOC response to a single dos e of metyrapone in VLBW infants after prolonged Dex therapy.