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The corticotrophin-releasing hormone test in preterm infants
Roel J Bolt1, Mirjam M van Weissenbruch, Anneke Cranendonk
1Research Institute of Endocrinology, Reproduction and Metabolism, VU University Medical Centre, Department of Pediatrics, Amsterdam, the Netherlands. roel.bolt@vumc.nl
Insights
A 2 microg/kg dose of corticotrophin-releasing hormone (CRH) effectively stimulates the pituitary-adrenal axis in preterm infants, unlike a 1 microg/kg dose. This finding is crucial for understanding adrenal function in premature neonates.
Area of Science:
- Neonatal endocrinology
- Pediatric endocrinology
- Reproductive biology
Background:
- The hypothalamic-pituitary-adrenal axis (HPAA) is often immature in preterm infants, potentially leading to inadequate stress responses.
- Limited data exists on the pituitary-adrenal response to corticotrophin-releasing hormone (CRH) stimulation in early neonatal periods for infants born before 32 weeks gestation.
Purpose of the Study:
- To investigate the pituitary-adrenal response to 1 microg/kg CRH i.v. in preterm infants (≤32 weeks gestation).
- To compare the pituitary-adrenal response to 1 microg/kg CRH, placebo, and 2 microg/kg CRH in a randomized controlled trial.
Main Methods:
- A study involving 13 preterm infants (≤32 weeks gestation) receiving 1 microg/kg CRH intravenously.
- A randomized placebo-controlled study comparing 1 microg/kg CRH, 2 microg/kg CRH, and placebo for pituitary-adrenal stimulation.
Main Results:
- 1 microg/kg CRH i.v. resulted in an inadequate adrenal response in 38% of infants for ACTH and 15% for cortisol.
- Both 1 microg/kg and 2 microg/kg CRH stimulated ACTH and cortisol levels (P < 0.01), but the 2 microg/kg dose yielded significantly higher levels.
- No significant difference in ACTH and cortisol was observed between the 1 microg/kg CRH group and the placebo group.
Conclusions:
- A 1 microg/kg CRH stimulation test frequently results in an inappropriate adrenal response in preterm infants.
- A 2 microg/kg CRH dose elicits an appropriate pituitary-adrenal response in all studied preterm infants.
- The dose of CRH is critical for adequate pituitary-adrenal axis stimulation in preterm neonates, potentially influenced by axis maturity.
Objective:
The developing hypothalamic--pituitary--adrenal axis (HPAA) may be immature and not yet fully functional in preterm infants. This may result in an inappropriate adrenal response to stress. Little is known about the pituitary--adrenal response to corticotrophin-releasing hormone (CRH) stimulation during the early neonatal period in preterm infants born before 32 weeks of gestation. Therefore, in a first study we investigated the pituitary--adrenal response to 1 microg/kg CRH i.v. in 13 preterm infants born less-than-or-equal 32 weeks of gestation. In addition, in a randomized placebo-controlled study we compared the pituitary--adrenal response of 1 microg/kg CRH to placebo and stimulation with 2 microg/kg CRH.
Results:
In the first study, the level of ACTH increased from 6.9 +/-2.1 to 11.6 +/- 5.1 pmol/l (P < 0.01) and cortisol increased from 350 plus minus 115 to 582 +/- 201 nmol/l (P < 0.05). Thirty-eight percent of the studied infants showed a maximal level of ACTH < 9 pmol/l, and 15% showed a maximal level of cortisol < 360 nmol/l. In the randomized study, infants in the 1 microg/kg and in the 2 microg/kg CRH group, but not in the placebo group, showed a significant increase in cortisol and ACTH after stimulation (P < 0.01). Stimulated levels of ACTH and cortisol were significantly higher in the 2 microg/kg group compared with the placebo and the 1 microg/kg group. No differences were found for plasma ACTH and cortisol levels in the 1 microg/kg group compared with the placebo group. Basal levels of cortisol and ACTH obtained from the first and from the randomized study correlated significantly (n = 29; r = 0.42, P < 0.03). In addition, in infants stimulated with 1 microg/kg CRH a lower cortisol response correlated with a longer stay in hospital (n = 13; r = --0.57, P < 0.05).
Conclusions:
In this study we show that a 1 microg/kg CRH stimulation test in preterm infants results more often in an inappropriate adrenal response while stimulation with 2 microg/kg CRH gives rise to an appropriate response in all studied infants. Furthermore, stimulation with 2 microg/kg CRH results in higher levels of ACTH and cortisol compared to placebo and 1 microg/kg CRH. We conclude that in preterm infants the ability of the pituitary to respond adequately to CRH stimulation depends on the dose of CRH used and may also be dependent on the maturity of the pituitary--adrenal axis.
