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.


METHODS
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 microg/dl; mean +/- SEM) than after (5.77 +/- 1.45 microg/dl; p < 0.01), as were ACTH-stimulated cortisol levels (24.8 +/- 1.7 microg/dl vs 12.0 +/- 2.2 microg/dl; p < 0.001). ACTH response to oCRH decreased after Dex treatment (22.8 +/- 7.6 pg/ml vs 11.5 +/- pg/ml), but this was not statistically significant (p = 0.18). 11-Deoxycortisol (11-DOC) response to metyrapone dropped from 11.1 +/- 0.5 microg/dl to 4.7 +/- 1.0 microg/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 microg/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.
Ford
L R
LR
Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.
Willi
S M
SM
Hollis
B W
BW
Wright
N M
NM
D000324:Adrenocorticotropic Hormone; D000893:Anti-Inflammatory Agents / Q000009:adverse effects*; D002908:Chronic Disease; D003346:Corticotropin-Releasing Hormone; D003907:Dexamethasone / Q000009:adverse effects*; D005865:Gestational Age; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D019102:Infant, Very Low Birth Weight; D008137:Longitudinal Studies; D008171:Lung Diseases / Q000175:diagnosis / Q000188:drug therapy; D008797:Metyrapone; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011863:Radioimmunoassay; D013997:Time Factors
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D008797:Metyrapone