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Impaired glucocorticoid synthesis in premature infants developing chronic lung disease
K L Watterberg1, J S Gerdes, K L Cook
1Department of Pediatrics, University of New Mexico, ACC 3-West, Albuquerque, NM 87131, U.S.A. kwatterberg@salud.unm.edu
Insights
Sick preterm infants who develop chronic lung disease (CLD) have lower cortisol levels and impaired cortisol synthesis. This suggests relative adrenal insufficiency may contribute to CLD development in premature infants.
Area of Science:
- Neonatal physiology
- Endocrinology
- Pulmonary medicine
Background:
- Premature infants often exhibit altered cortisol metabolism compared to term infants.
- Sick preterm infants, particularly those developing chronic lung disease (CLD), present with paradoxically low cortisol concentrations.
- This suggests a potential impairment in cortisol synthesis capacity.
Purpose of the Study:
- To investigate the hypothesis that decreased cortisol synthesis contributes to CLD in extremely low birth weight (ELBW) infants.
- To assess steroid hormone profiles and adrenal function in ELBW infants with and without CLD.
Main Methods:
- Measurement of cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, and ACTH in 40 ELBW infants.
- Analysis of steroid concentrations and ratios before and after low-dose hydrocortisone therapy.
- Comparison of hormonal profiles between infants who developed CLD and those who recovered.
Main Results:
- Infants who developed CLD had lower basal and stimulated cortisol levels compared to recovered infants.
- Elevated cortisol precursors (17-hydroxyprogesterone) and precursor-to-product ratios (17-OHP/11-deoxycortisol, 11-deoxycortisol/cortisol) were observed in CLD infants.
- Hydrocortisone therapy did not suppress ACTH or measured steroid levels.
Conclusions:
- ELBW infants who develop CLD exhibit evidence of impaired cortisol synthesis, indicated by lower cortisol and elevated precursor levels.
- These findings support the hypothesis of relative adrenal insufficiency contributing to CLD pathogenesis in this vulnerable population.
- Further research into adrenal function is warranted for managing and preventing CLD in preterm infants.
Abstract:
Premature infants have higher cortisol precursor concentrations than term infants; however, many sick preterm infants have surprisingly low cortisol concentrations. Those who develop chronic lung disease (CLD) have lower cortisol values than those who recover. We hypothesized that some infants have a decreased ability to synthesize cortisol, leading to physiologic disruptions including amplified inflammatory responses, thereby resulting in CLD. We measured cortisol, 11-deoxycortisol, 17-hydroxyprogesterone, 17-hydroxypregnenolone, dehydroepiandrosterone sulfate, and ACTH in 40 extremely low birth weight infants enrolled in a study of low-dose hydrocortisone therapy to prevent CLD. Thirty-four infants survived and 15 developed CLD. Hydrocortisone therapy did not suppress ACTH or any measured steroid value. Before study (<48 h of life), 17-OH progesterone was higher in CLD infants, as was the ratio of 17-OH progesterone to 11-deoxycortisol. On d 15-19 (> or =72 h after end of therapy), basal and stimulated cortisol concentrations were lower in CLD infants. In contrast, the basal ratio of 11-deoxycortisol to cortisol was higher in CLD infants, as were stimulated values of 17-OH progesterone and stimulated ratios of 17-OH progesterone to 11-deoxycortisol and 11-deoxycortisol to cortisol. Thus, infants who developed CLD had lower basal and stimulated cortisol values, but elevated cortisol precursors and precursor to product ratios, compared with infants who recovered. These data support the hypothesis that these immature infants have a decreased capacity to synthesize cortisol, which may lead to a relative adrenal insufficiency in the face of significant illness.