Cortisol Levels During Acute Illnesses in Children and Adolescents: A Systematic Review

IMPORTANCE: Endogenous cortisol levels in children and adolescents during acute illnesses can contribute to the evidence base required to optimize glucocorticoid (GC) stress doses for children and adolescents known to have GC deficiency. OBJECTIVE: To identify endogenous cortisol levels during a range of acute illnesses in children and adolescents without GC deficiency from published evidence. EVIDENCE REVIEW: CINAHL, Cochrane Library, Cochrane Database of Systematic Reviews, Embase, and MEDLINE were searched for studies published between January 1, 2000, and June 30, 2020. Two reviewers independently identified relevant studies. Differences were resolved by joint discussion. Inclusion criteria were common acute illnesses, age from 1 month to 18 years, and basal blood cortisol levels obtained within 48 hours of presentation. Studies with fewer than 5 participants and those that included participants known to have GC deficiency or a history of treatment that could affect cortisol levels were excluded from the review. Data for predefined fields were extracted and independently checked by separate pairs of reviewers. Overall weighted means and pooled SDs for cortisol levels were calculated. FINDINGS: All 15 studies included were hospital based and included 864 unique participants: 14 studies were prospective observational studies, 1 was part of a trial, and 5 included control individuals. Mean cortisol levels were higher in all participants with an acute illness (n = 689) than in controls (n = 175) (difference in weighted means, 18.95 μg/dL; 95% CI, 16.68-21.22 μg/dL). Cortisol levels were highest in patients with bacterial meningitis (weighted mean [pooled SD], 46.42 [22.24] μg/dL) and were more than 3-fold higher in the group with severe gastroenteritis (weighted mean [pooled SD], 39.64 [21.34] μg/dL) than in the control group. Among the subgroups with sepsis, those with shock had lower cortisol levels than those without shock (weighted mean [pooled SD], 27.83 [36.39] μg/dL vs 37.00 [23.30] μg/dL), but levels in nonsurvivors did not differ from levels in survivors (weighted mean [pooled SD], 24.89 [51.65] μg/dL vs 30.53 [30.60] μg/dL). CONCLUSIONS AND RELEVANCE: This systematic review found that, in children and adolescents without GC deficiency, circulating cortisol levels were higher during acute illnesses than those in controls and also varied across a range of acute illnesses. Whether these levels need to be achieved with exogenous GC stress doses tailored according to the nature and severity of the illness in children and adolescents with GC deficiency warrants investigation.