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Inflammatory biomarkers in the evaluation of pediatric endogenous Cushing syndrome
Rachel Wurth1, Megan Rescigno1, Chelsi Flippo1
1Section on Endocrinology & Genetics (SEGEN), Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), National Institutes of Health (NIH), Bethesda, Maryland, USA.
Insights
Patients with Cushing syndrome (CS) show altered inflammatory biomarkers, including higher neutrophil-to-lymphocyte ratio (NLR). These markers correlate with cortisol levels, indicating hypercortisolemia impacts the immune system.
Area of Science:
- Endocrinology
- Immunology
- Clinical Diagnostics
Background:
- Inflammatory biomarkers like neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are linked to various disease progressions.
- Cushing syndrome (CS) is associated with immunosuppression and altered leukocyte counts, yet its inflammatory biomarker profile remains under-researched.
Purpose of the Study:
- To investigate and compare a panel of inflammatory biomarkers in patients with active endogenous Cushing syndrome (CS) against a control group.
- To assess the correlation between these inflammatory biomarkers and indicators of cortisol secretion in CS patients.
Main Methods:
- A comparative analysis of inflammatory biomarkers was conducted using complete blood count (CBC) data from 319 patients with active endogenous CS and 93 eucortisolemic controls.
- Participants were stratified into two age groups (6-12 years and >12 years) to account for age-related variations in reference ranges.
Main Results:
- Patients with CS exhibited significantly higher neutrophil-to-lymphocyte ratio (NLR) compared to controls across both age groups (P < 0.0001).
- Absolute neutrophil and lymphocyte counts, MLR, and PLR also showed significant differences between CS patients and controls.
- NLR demonstrated a high diagnostic accuracy, with area under the curve (AUC) values of 0.77 and 0.81 for the younger and older age groups, respectively.
Conclusions:
- Multiple inflammatory biomarkers are significantly altered in patients with Cushing syndrome compared to controls.
- These findings suggest that hypercortisolemia exerts substantial effects on the immune system, impacting inflammatory profiles.
Objective:
Inflammatory biomarkers, such as absolute neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), platelet (PLT)-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), are associated with the progression and development of several disorders. Although patients with Cushing syndrome (CS) have immunosuppression with altered leucocyte counts, the profile of the inflammatory biomarkers in these patients has not been extensively studied.
Design:
We compared a panel of inflammatory biomarkers in patients with active endogenous CS (n of complete blood count (CBC) reports = 319) and eucortisolemic subjects of similar age, gender and BMI (n of CBC reports = 93). Patients were divided into two age groups (6-12 years at the time of CBC and >12 years at the time of CBC) based on age differences in normal reference ranges.
Results:
Patients with CS had higher NLR vs controls (6-12 years: 2.47 (1.86, 3.32) vs 1.35 (1.11, 2.27), P < 0.0001; >12 years: 3.00 (2.23-4.17) vs 1.80 (1.23-2.31), P < 0.0001). Similarly, absolute neutrophil and lymphocyte counts, MLR and PLR differed between patients with CS and controls. The inflammatory biomarkers correlated with indices of cortisol secretion, such as midnight serum cortisol, 24-h urinary free cortisol and morning cortisol. On receiver operating characteristic analysis, NLR showed high area under the curve (AUC) (6-12 years: cutoff of 1.72 had AUC: 0.77, >12 years: cutoff of 2.35 had AUC: 0.81).
Conclusions:
We conclude that multiple inflammatory biomarkers differed between patients with CS and controls suggesting substantial effects of hypercortisolemia on the immune system.
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