Random serum free cortisol and total cortisol measurements in pediatric septic shock
-
Kusum Menon
,
Dayre McNally
Abstract
Background
The aim of the study was to examine the relationship between serum total cortisol (TC) and free cortisol (FC) levels in children with septic shock and the relationship of these levels with baseline illness severity.
Methods
A sub-study of a randomized controlled trial (RCT) of hydrocortisone vs. placebo in pediatric septic shock conducted in seven academic pediatric intensive care units (PICUs) in Canada on children aged newborn to 17 years. Thirty children with septic shock had serum sent for TC and FC measurement within 6 h of meeting the study eligibility criteria.
Results
Baseline FC and TC levels were strongly correlated with baseline Pediatric Risk of Mortality (PRISM) score (R2=0.759, p<0.001; R2=0.717, p<0.001) and moderately correlated with admission Vasotropic Inotropic Score (VIS) (R2=0.489, p<0.001; R2=0.316, p<0.001). Serum TC levels were highly correlated with FC levels (R2=0.92, p<0.001) and showed strong agreement (R2=0.98, p<0.001 on a Bland-Altman plot). The ratio of FC to TC moderately correlated with TC levels (R2=0.46, p<0.001) but did not correlate with baseline albumin levels (R2=0.19, p=0.13).
Conclusions
Random TC and FC levels are strongly correlated, show strong agreement and are reflective of illness severity in children with septic shock. As such, isolated FC measurement does not appear to provide added information relative to TC in acutely ill children with septic shock.
Funding source: Canadian Institutes of Health Research
Award Identifier / Grant number: MOP 133405 to KM
Funding statement: This work was supported by the Canadian Institutes of Health Research (CIHR), Canada, Funder Id: 10.13039/501100000024 (MOP 133405 to KM).
Acknowledgments
The authors wish to thank the CCCTG for the grant and manuscript review and Drs. Brent Winston and Waleed Al-Hazzani for their valuable appraisals. In addition, the authors are grateful to the research assistants, coordinators, families and patients at the participating sites.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Annane D. Defining critical illness-related corticosteroid insufficiency: one step forward! Crit Care Med 2010;38:721–2.10.1097/CCM.0b013e3181c54620Search in Google Scholar PubMed
2. Menon K, Ward RE, Lawson ML, Gaboury I, Hutchison JS, et al. A prospective multicenter study of adrenal function in critically ill children. Am J Respir Crit Care Med 2010;182:246–51.10.1164/rccm.200911-1738OCSearch in Google Scholar PubMed PubMed Central
3. Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862–71.10.1001/jama.288.7.862Search in Google Scholar PubMed
4. Sprung CL, Annane D, Keh D, Moreno R, Singer M, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111–24.10.1056/NEJMoa071366Search in Google Scholar PubMed
5. Menon K, McNally JD, Choong K, Ward R, Lawson M, et al. A survey of stated physician practices and beliefs on the use of steroids in pediatric fluid and/or vasoactive infusion-dependent shock. Pediatr Crit Care Med 2013;14:462–6.10.1097/PCC.0b013e31828a7287Search in Google Scholar PubMed
6. Menon K, McNally JD, Choong K, Lawson M, Ramsay T, et al. A cohort study of pediatric shock: frequency of corticosteriod use and association with clinical outcomes. Shock 2015;44:402–9.10.1097/SHK.0000000000000355Search in Google Scholar PubMed
7. Yehya N, Vogiatzi MG, Thomas NJ, Srinivasan V. Cortisol correlates with severity of illness and poorly reflects adrenal function in pediatric acute respiratory distress syndrome. J Pediatr 2016;177:212–8.10.1016/j.jpeds.2016.05.020Search in Google Scholar PubMed PubMed Central
8. Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med 2004;350:1629–38.10.1056/NEJMoa020266Search in Google Scholar PubMed
9. Beishuizen A, Thijs LG, Vermes I. Patterns of corticosteroid-binding globulin and the free cortisol index during septic shock and multitrauma. Intensive Care Med 2001;27:1584–91.10.1007/s001340101073Search in Google Scholar PubMed
10. Ho JT, Al-Musalhi H, Chapman MJ, Quach T, Thomas PD, et al. Septic shock and sepsis: a comparison of total and free plasma cortisol levels. J Clin Endocrinol Metab 2006;91:105–14.10.1210/jc.2005-0265Search in Google Scholar PubMed
11. Cohen J, Smith ML, Deans RV, Pretorius CJ, Ungerer JP, et al. Serial changes in plasma total cortisol, plasma free cortisol, and tissue cortisol activity in patients with septic shock: an observational study. Shock 2012;37:28–33.10.1097/SHK.0b013e318239b809Search in Google Scholar PubMed
12. den Brinker M, Joosten KF, Liem O, de Jong FH, Hop CJ, et al. Adrenal insufficiency in meningococcal sepsis: bioavailable cortisol levels and impact of interleukin-6 levels and intubation with etomidate on adrenal function and mortality. J Clin Endocrinol Metab 2005;90:5110–7.10.1210/jc.2005-1107Search in Google Scholar PubMed
13. Zimmerman JJ, Donaldson A, Barker RM, Meert KL, Harrison R, et al. Real-time free cortisol quantification among critically ill children. Pediatr Crit Care Med 2011;12:525–31.10.1097/PCC.0b013e3181fe4474Search in Google Scholar PubMed PubMed Central
14. Menon K, McNally D, O’Hearn K, Acharya A, Wong H, et al. A randomized controlled trial of corticosteroids in pediatric septic shock: a pilot feasibility study. Pediatr Crit Care Med 2017;18:505–12.10.1097/PCC.0000000000001121Search in Google Scholar PubMed PubMed Central
15. O’Hearn K, McNally D, Choong K, Acharya A, Wong H, et al. Steroids in fluid and/or vasoactive infusion dependent pediatric shock: study protocol for a randomized controlled trial. Trials 2016;17:238.10.1186/s13063-016-1365-6Search in Google Scholar PubMed PubMed Central
16. Pollack MM, Patel KM, Ruttimann UE. PRISM III: an updated pediatric risk of mortality score. Crit Care Med 1996;24:743–52.10.1097/00003246-199605000-00004Search in Google Scholar PubMed
17. Haque A, Siddiqui NR, Munir O, Saleem S, Mian A. Association between vasoactive-inotropic score and mortality in pediatric septic shock. Indian Pediatr 2015;52:311–3.10.1007/s13312-015-0630-1Search in Google Scholar PubMed
18. Zimmerman JJ, Barker RM, Jack R. Initial observations regarding free cortisol quantification logistics among critically ill children. Intensive Care Med 2010;36:1914–22.10.1007/s00134-010-2007-1Search in Google Scholar PubMed
19. Gunnala V, Guo R, Minutti C, Durazo-Arveizu R, Laporte C, et al. Measurement of salivary cortisol level for the diagnosis of critical illness-related corticosteroid insufficiency in children. Pediatr Crit Care Med 2015;16:e101–6.10.1097/PCC.0000000000000361Search in Google Scholar PubMed
20. Indyk JA, Candido-Vitto C, Wolf IM, Venkataram S, Munoz R, et al. Reduced glucocorticoid receptor protein expression in children with critical illness. Horm Res Paediatr 2013;79:169–78.10.1159/000348290Search in Google Scholar PubMed
21. Zimmerman JJ, Williams MD. Adjunctive corticosteroid therapy in pediatric severe sepsis: observations from the RESOLVE study. Pediatr Crit Care Med 2011;12:2–8.10.1097/PCC.0b013e3181d903f6Search in Google Scholar PubMed
22. Hatherill M, Tibby SM, Hilliard T, Turner C, Murdoch IA. Adrenal insufficiency in septic shock. Arch Dis Child 1999;80:51–5.10.1136/adc.80.1.51Search in Google Scholar PubMed PubMed Central
23. Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003;348:727–34.10.1056/NEJMra020529Search in Google Scholar PubMed
24. Bone M, Diver M, Selby A, Sharpeless M, Addison M, et al. Assessment of adrenal function in the initial phase of meningococcal disease. Pediatrics 2002;110:563–9.10.1542/peds.110.3.563Search in Google Scholar PubMed
25. Dickstein G, Shechner C, Nicholson WE, Rosner I, Shen-Orr Z, et al. Adrenocorticotropin stimulation test: effects of basal cortisol level, time of day, and suggested new sensitive low dose test. J Clin Endocrinol Metab 1991;72:773–8.10.1210/jcem-72-4-773Search in Google Scholar PubMed
26. Bornstein SR, Licinio J, Tauchnitz R, Engelmann L, Negrao AB, et al. Plasma leptin levels are increased in survivors of acute sepsis: associated loss of diurnal rhythm, in cortisol and leptin secretion. J Clin Endocrinol Metab 1998;83: 280–3.10.1210/jcem.83.1.4610Search in Google Scholar PubMed
©2018 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Review
- Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis
- Original Articles
- Can having a sibling with type 1 diabetes cause disordered eating behaviors?
- Wrist circumference as a novel predictor of obesity in children and adolescents: the CASPIAN-IV study
- Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance
- Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents
- Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center
- Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin
- Random serum free cortisol and total cortisol measurements in pediatric septic shock
- Self-assessment of pubertal development in a puberty cohort
- Growth, the Mediterranean diet and the buying power of adolescents in Greece
- Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
- Genetic analysis of three families with X-linked dominant hypophosphatemic rickets
- Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases
- No central adrenal insufficiency found in patients with Prader-Willi syndrome with an overnight metyrapone test
- Case Reports
- A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index
- Hypertriglyceridemia thalassemia syndrome
- Severe consumptive hypothyroidism caused by multiple infantile hepatic haemangiomas
Articles in the same Issue
- Frontmatter
- Review
- Prevalence of cranial MRI findings in girls with central precocious puberty: a systematic review and meta-analysis
- Original Articles
- Can having a sibling with type 1 diabetes cause disordered eating behaviors?
- Wrist circumference as a novel predictor of obesity in children and adolescents: the CASPIAN-IV study
- Evaluation of Mn-superoxide dismutase and catalase gene expression in childhood obesity: its association with insulin resistance
- Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents
- Clinical management of childhood hyperthyroidism with and without Down syndrome: a longitudinal study at a single center
- Detection of distant metastasis at the time of ablation in children with differentiated thyroid cancer: the value of pre-ablation stimulated thyroglobulin
- Random serum free cortisol and total cortisol measurements in pediatric septic shock
- Self-assessment of pubertal development in a puberty cohort
- Growth, the Mediterranean diet and the buying power of adolescents in Greece
- Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
- Genetic analysis of three families with X-linked dominant hypophosphatemic rickets
- Clinical heterogeneity and molecular profile of triple A syndrome: a study of seven cases
- No central adrenal insufficiency found in patients with Prader-Willi syndrome with an overnight metyrapone test
- Case Reports
- A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index
- Hypertriglyceridemia thalassemia syndrome
- Severe consumptive hypothyroidism caused by multiple infantile hepatic haemangiomas
