ACTH and cortisol response to critical illness in term and late preterm newborns

Abstract

Objective: To determine cortisol and adrenocorticotropic hormone (ACTH) responses to critical illness in term and late preterm newborns and examine the relationship of these values to measures of clinical illness, including markers of cardiovascular dysfunction.

Study design: In this prospective observational study, we measured ACTH, baseline cortisol and ACTH-stimulated cortisol concentrations in mechanically ventilated infants >or=34 weeks gestational age and <5 postnatal days. ACTH-stimulated cortisol concentrations were also measured in a comparison group of non-critically ill, non-mechanically ventilated infants. The relationship of these values to measures of severity of illness including SNAP (score for neonatal acute physiology) scores, blood pressure and vasopressor initiation was examined.

Result: Concentrations are presented as median (25th to 75th percentile). Baseline cortisol values in critically ill infants (n=35) were 4.6 microg per 100 ml (3.0 to 16.2); 26 (74%) of these were <15 microg per 100 ml. ACTH-stimulated cortisol values were not significantly different from the comparison group (41 microg per 100 ml (30.3 to 51.8) vs 34.2 microg per 100 ml (25.2 to 43.3)). ACTH concentrations in ill infants (n=10) were 12 pgml(-1) (5.5 to 19.2). None of baseline cortisol, stimulated cortisol and ACTH increased significantly with increasing severity of illness. Of the ill infants, 71% received vasopressor therapy for hypotension. Cortisol concentrations in these infants were similar to those infants who did not receive vasopressor therapy.

Conclusion: The majority of these critically ill newborns had very low cortisol and ACTH values without the expected increase in response to critical illness; however, their response to exogenous ACTH was normal. These results demonstrate that the inadequate response to critical illness in these newborns does not result from adrenal dysfunction. We therefore hypothesize that this is a secondary insufficiency arising from inadequate stimulation of the adrenal gland.

Figure 1

Critically ill infants. A. SNAP vs. baseline cortisol (1 cortisol value of 99 mcg/dl not shown but included in analysis); B. SNAP vs. ACTH-stimulated cortisol (2 values of 103 and 130 mcg/dl not shown but included in analysis); C. SNAP vs. ACTH. Analyzed with Spearman’s correlation (ρ).

Figure 2

Critically ill infants. Lowest mean blood pressure 24 hours before or 24 hours after baseline cortisol vs. baseline cortisol. Analyzed with Spearman’s correlation (ρ).