Evaluation of the Hypothalamic-Pituitary-Adrenal Axis in a Paediatric Intensive Care Unit

Abstract

Background. Relative adrenal insufficiency (RAI) is the inadequate production of cortisol due to dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis during a severe illness. We evaluated the HPA axis and RAI in a tertiary pediatric intensive care unit (PICU).Methods. A total of 100 PICU patients were included in this prospective cohort study. Basal serum levels of adrenocorticotropic hormone (ACTH), cortisol values were compared with those in the control group. A low-dose ACTH stimulation test was performed in patients with basal cortisol levels below 18 µg/dL.Results. The basal cortisol levels of the PICU patients were significantly higher than those of the control group (P < 0.05). All tested patients (n= 24) had delta cortisol levels > 9 µg/dL and a peak cortisol response > 18 µg/dL. Basal cortisol levels were positively correlated with Pediatric Risk of Mortality (PRISM) III scores (P < 0.05; r = 0.363). The basal or stimulated cortisol levels of the patients who received glucocorticoid treatment were higher than the cut-off levels.Conclusions. High basal or stimulated cortisol levels are indicative of disease severity in the acute phase of stress. Patients with very high cortisol levels should be particularly carefully monitored because of the high mortality risk.

Cortisol levels associated with mortality in children with critical illness: a systematic review

“…A total of 21 observational studies published before 2022 were analyzed, with a total of 2,212 enrolled subjects, of whom 57.97% were male and 42.03% were female. 5,6,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] The sample consisted of 1,810 subjects with critical illness, including 916 subjects with sepsis and septic shock, and 402 control subjects. The characteristics and outcomes of included studies are shown in Tables 1 and 2, respectively.…”

“…Nineteen of 21 studies stated that there was a relationship between elevated cortisol levels and mortality in critical illness patients, including those with sepsis, as shown in Table 3. 5,6,[13][14][15][16][17][19][20][21][22][24][25][26][27][28][29][30] One study agreed with the statement, but found no relationship between postserum ACTH stimulation test and mortality in critical illness patients. 17 Fourteen studies had mortality percentage data critical illness patients with elevated cortisol levels.…”

“…17 Fourteen studies had mortality percentage data critical illness patients with elevated cortisol levels. 5,6,[13][14][15][16][17][18][19][20][25][26][27] Descriptive analysis on these 14 studies revealed a median mortality of 25.81 (range 2.7-60)% in critical illness patients. Only 7 studies had mortality rates of sepsis and septic shock patients with elevated cortisol levels.…”

“…2 This finding seems to be suggested in 19 studies included in this systematic review. 5,6,[13][14][15][16][17][19][20][21][22][24][25][26][27][28][29][30] One study noted an association between increased basal serum cortisol levels and mortality in critically ill children, but no relationship between post-ACTH stimulation serum cortisol levels and mortality in critically ill children. Levy-Shraga et al 17 stated that the non-survival group had higher basal serum cortisol levels than the survivor group (mean 22.58 and 12.79 g/dL, respectively; P=0.05), but no significant difference in post-test serum cortisol levels ACTH stimulation in both groups.…”

Critical illness-related corticosteroid insufficiency (CIRCI) in paediatric patients: a diagnostic and therapeutic challenge

“…It has been observed that the presence of adrenal failure in patients with a septic state (including both sepsis and septic shock) is associated with increased mortality and a long duration of intensive care unit stay. It also seems that the need for inotropic support and high doses of inotropic drugs might be considered as an indicator of adrenal insufficiency in ICU patients [ 8 ].…”