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Suppression and recovery of the neonatal hypothalamic-pituitary-adrenal axis after prolonged dexamethasone therapy
L R Ford1, S M Willi, B W Hollis
1Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.
Insights
Prolonged dexamethasone treatment in premature infants with chronic lung disease suppresses the hypothalamic-pituitary-adrenal (HPA) axis. Recovery of higher HPA centers is delayed, necessitating careful monitoring with tests like metyrapone stimulation.
Area of Science:
- Neonatal Medicine
- Endocrinology
- Pediatric Pulmonology
Background:
- Premature infants often require glucocorticoid therapy for chronic lung disease.
- Prolonged glucocorticoid use can lead to hypothalamic-pituitary-adrenal (HPA) axis suppression.
- Understanding the extent and duration of HPA axis suppression is crucial for managing these vulnerable infants.
Purpose of the Study:
- To evaluate the duration and level of HPA axis suppression in premature infants receiving prolonged dexamethasone treatment.
- To assess the recovery patterns of adrenal and pituitary function after dexamethasone therapy.
Main Methods:
- HPA axis function was assessed in very low birth weight (VLBW) infants before and after a 14-42 day course of dexamethasone.
- Adrenal, pituitary, and combined axis function were evaluated using synthetic adrenocorticotropic hormone (ACTH) stimulation, ovine corticotrophin releasing hormone (oCRH) stimulation, and metyrapone testing.
- Serial testing was performed in a subset of infants to determine the time course of HPA axis recovery.
Main Results:
- Dexamethasone therapy significantly reduced baseline and ACTH-stimulated cortisol levels.
- While adrenal suppression appeared short-lived, the response of higher HPA axis centers, assessed by 11-deoxycortisol (11-DOC) after metyrapone, was significantly blunted.
- Longitudinal data indicated delayed recovery of pituitary and central HPA axis function.
Conclusions:
- Basal cortisol levels can serve as an initial screening tool, but levels below 15 microg/dl warrant further investigation.
- Metyrapone testing, specifically measuring 11-DOC response, is a reliable method to evaluate the recovery of higher HPA axis centers in VLBW infants post-dexamethasone therapy.
- The findings highlight the importance of monitoring HPA axis function in premature infants after prolonged glucocorticoid treatment.
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 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.