Elsevier

The Journal of Pediatrics

Volume 131, Issue 5, November 1997, Pages 722-726
The Journal of Pediatrics

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

Presented in part at the 65th Annual Meeting of the Society for Pediatric Research in Washington, DC; May 2-5, 1996.
https://doi.org/10.1016/S0022-3476(97)70100-8Get rights and content

Abstract

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 μg/dl; mean ± SEM) than after (5.77 ± 1.45 μg/dl; p < 0.01), as were ACTH-stimulated cortisol levels (24.8 ± 1.7 μg/dl vs 12.0 ± 2.2 μg/dl; p < 0.001). ACTH response to oCRH decreased after Dex treatment (22.8 ± 7.6 ρg/ml vs 11.5 ± ρg/ml), but this was not statistically significant ( p = 0.18). 11-Deoxycortisol (11-DOC) response to metyrapone dropped from 11.1 ± 0.5 μg/dl to 4.7 ± 1.0 μg/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 μg/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. (J Pediatr 1997;131:722-26)

Section snippets

Subjects

Nine VLBW infants (four girls) in the neonatal intensive care unit at the Medical University of South Carolina who required ventilator support for early chronic lung disease were recruited after their parents gave informed consent. All the infants began a standard Dex treatment course (42 days, tapering doses) as part of their respiratory treatment. 1 The infants were 19.9 ± 8.0 (mean ± SD) days old at study entry; the average gestational age was 25.7 ± 1.0 weeks, and their weights were

Basal Cortisol Values

Basal cortisol levels were higher before Dex therapy (18.61 ± 3.92 μg/dl; mean ± SEM) than after (5.77 ± 1.45 μg/dl, p < 0.01). A baseline cortisol level of 15 μg/dl was seen in seven of nine infants before Dex therapy, compared with zero of nine infants having a level of 15 μg/dl or greater in the posttreatment group (Fig. 1).

. Comparison of basal cortisol levels before and after Dex therapy. Circles , Full 42-day Dex treatment; triangles , truncated Dex course.

Cortisol Values after ACTH

ACTH-stimulated cortisol levels

Discussion

High-dose glucocorticoid treatment has become a part of standard neonatal respiratory management of early chronic lung disease in the absence of a complete understanding of the adverse effects of this therapy on HPA axis function. Furthermore, normal HPA axis function in the VLBW infant remains poorly defined. Amid the myriad of tests evaluating HPA axis function, little consensus regarding normal function in the newborn infant exists.

Our results demonstrate that suppression of the HPA axis

Acknowledgements

We thank the staffs of the General Clinical Research Center and Neonatal Intensive Care Unit at the Medical University of South Carolina and L. Clewell, PharmD, for their invaluable assistance.

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    Supported by grant no. MO1RR01070 from the National Institutes of Health and a Neonatology Fellows research grant from Wyeth Laboratories (Dr. Ford).

    ☆☆

    Reprint requests: Steven M. Willi, MD, Department of Pediatrics, Medical University of South Carolina, 171 Ashley Ave., Charleston, SC 29425.

    0022-3476/97/$5.00 + 0 9/21/81207

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