Acute illness increases cortisol levels in children and adolescents

A new JAMA Network Open study reports that in children and adolescents without glucocorticoid (GC) deficiency, circulating cortisol levels were higher during acute illnesses as compared to when they were otherwise healthy. Notably, cortisol levels also varied across different types of acute illnesses.

Study: Cortisol Levels During Acute Illnesses in Children and Adolescents. Image Credit: Axel_Kock /

Study: Cortisol Levels During Acute Illnesses in Children and Adolescents. Image Credit: Axel_Kock /


Acute illnesses can have a significant impact on an individual’s well-being and may even threaten their survival. These acute physical events typically initiate a physiological stress response involving the hypothalamic-pituitary-adrenal axis to attain homeostasis.

This acute stress response leads to a rapid increase in cortisol secretion, which affects the intravascular blood volume, glucose metabolism, and cardiovascular function. This fight-or-flight response is altered in individuals with a glucocorticoid (GC) deficiency, thus increasing the risk that an acute adrenal crisis will occur. Thus, researchers have hypothesized that GC replacement therapy could induce a reaction similar to the increased cortisol release that is normally triggered by stress.

The standard clinical protocols for ‘stress’ or ‘sick day’ doses in the prevention of an adrenal crisis involve double or triple GC replacement doses. However, there remains limited evidence supporting this approach, as well as what doses would be appropriate for this type of treatment in both children and adolescents.

About the study

The current systematic review was performed according to the Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The Healthcare Databases Advanced Search (HDAS) platform was utilized for the search, which included CINAHL, Cochrane Database of Systematic Reviews, Cochrane Library, Embase, and MEDLINE databases. 

Overall, 15 hospital-based studies comprising 864 participants were selected for the study. Among these, 14 were prospective observational studies and one was part of a clinical trial. Patients treated with etomidate were excluded from one study. 

Study findings

None of the reviewed studies reported febrile illness, vomiting, viral infection, urinary tract infection (UTI), otitis media, and upper or lower respiratory infection (URTI/LRTI). Patients were categorized based on the severity of acute illness. Each subgroup consisted of a small number of studies, except for sepsis.  

In the five studies that included control groups, cortisol levels within the blood were acquired between 8 and 9 A.M. These measurements were primarily assessed by nonisotopic immunoassays including chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and radioimmunoassay.

Higher cortisol levels were observed in all groups as compared to controls, with the highest levels exceeding four-fold detected among those with bacterial meningitis when compared to controls.  The lowest cortisol levels were recorded in patients with mild or moderate bronchiolitis.

In the subgroup with sepsis, among those with shock, lower cortisol levels were detected as compared to those without shock. Of note, survivors exhibited equivalent cortisol levels as compared to nonsurvivors. 

Meanwhile, higher cortisol levels were detected in patients with severe gastroenteritis who required intravenous fluid rehydration as compared to those with bronchiolitis, sepsis, or other critical illness. However, the cortisol levels in the combined subgroups with noncritical illnesses were not significantly different from those of patients with critical illnesses, including sepsis. 


The study findings indicate that the intact hypothalamic-pituitary-adrenal axes of children and adolescents caused higher circulating cortisol levels during episodes of acute illness when compared to controls. This effect varied with the types of acute illnesses.

Extensive studies in the future are needed to ascertain whether equivalent cortisol levels are essential when gained from exogenous GC treatment among children and adolescents with GC deficiency who experienced episodes of acute illnesses. 

Journal reference:
Nidhi Saha

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.


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