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Pediatrics International (2014) 56, 349–353
doi: 10.1111/ped.12269
Original Article
Evaluation of endocrine function in children admitted to pediatric intensive care unit Banu Küçükemre Aydın,1 Demet Demirkol,2 Firdevs Bas¸,1 Ümit Türkog˘lu,3 Alkın Kumral,3 Metin Karaböcüog˘lu,2 Agop Çıtak2 and Feyza Darendeliler1 1 Department of Pediatrics, Pediatric Endocrinology Unit, 2Department of Pediatrics, Pediatric Intensive Care Unit, and 3 Department of Biochemistry, Faculty of Medicine, Istanbul University, Istanbul, Turkey Abstract
Background: Although studied widely in adulthood, little is known about endocrinological disorders during critical illnesses in childhood. The aims of this study were to define the endocrinological changes in patients admitted to pediatric intensive care unit (PICU) and to identify their effects on prognosis. Methods: Forty patients with a mean age of 5.1 years admitted to PICU were enrolled in the study. Blood samples were taken at admission and at 24 and 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient’s condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores. Results: PRISM and PELOD scores were significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP-3 and IL-6 were not significantly different between the survivors and non-survivors. There was a negative correlation between baseline IGFBP-3 and PRISM scores. A positive correlation was seen between cortisol level at 24 h and PRISM score. On multivariate linear regression analysis, PRISM score was best explained by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL-6 at 24 h and PELOD scores. Conclusions: Although there was no difference between survivors and non-survivors regarding the studied endocrine parameters, there were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment scores, and, given that these scores correlated with mortality, these parameters might be useful as prognostic factors.
Key words adrenocorticotropic hormone, cortisol, growth hormone, pediatric intensive care, prolactin.
Critical illness is a condition in which patients depend on intensive medical support of vital organ functions in order to survive. Endocrinological and metabolic changes can occur and may affect the prognosis and outcome during this life-threatening situation. Critically ill patients are in a state of extreme physiological stress, with changes in inflammatory pathways, tissue perfusion, and resulting multi-organ dysfunction. These physiological responses, along with interventions at the intensive care unit (ICU), result in a dynamic endocrine response. Basal hormone levels are different in this state due to factors such as changes in secretion, loss of negative feedback, altered target tissue receptor function and impaired enzymatic clearance.1 In critically ill children, disease course and outcome differ from adults.2 Some studies suggest that specific endocrine dysfunction is an age-related phenomenon.2,3 Although studied widely in adulthood, data on endocrinological changes during critical
Correspondence: Banu Küçükemre Aydın, MD, Istanbul University, Istanbul Faculty of Medicine, Istanbul Tip Fakultesi, Pediatrik Endokrinoloji Bilim Dali, Capa 34093, Istanbul, Turkey. Email: [email protected] Received 6 June 2013; revised 24 October 2013; accepted 13 November 2013.
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
illnesses in childhood are scarce. These changes must be investigated in order to construct a treatment strategy. We undertook this prospective study to further expand the knowledge on endocrine derangements in pediatric intensive care unit (PICU) patients. The objectives were to define the type of endocrinological changes appearing in these patients and to identify their effect on prognosis.
Methods Children admitted to the PICU at Istanbul University Hospital within a 15 month period were enrolled in this study. Patients who did not have a prior history of endocrinological disease were considered eligible for recruitment. Forty patients with a mean age of 5.1 years (median, 3.7 years; range, 1 month–15.9 years) were evaluated. Age and gender, and reason for PICU admission were recorded. Patients were divided into five subgroups according to reason for admission. Reasons for admission were cardiopulmonary insufficiency, sepsis, acute change in level of consciousness, liver insufficiency and gastrointestinal bleeding. The severity of the patient’s condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores.4,5 Mortality and morbidity were recorded. Results were summarized collectively and individually
350
BK Aydın et al.
for the subgroups and compared according to survival status and presence or absence of sequela. Blood samples were taken at admission, at 24 h and at 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). Sera were stored at −80°C until all samples were completed. The samples were run in the same assays using the same kits. Cortisol and prolactin were measured on electrochemiluminescence immunoassay (COBAS; Roche Diagnostics, Mannheim, Germany). For the cortisol kit the lowest limit of detection was 0.018 μg/dL, and intra- and interassay coefficients of variation (CV) were 1.0–1.3% and 1.4–1.6%, respectively. For the prolactin kit the lowest limit of detection was 0.047 ng/mL, and intra- and interassay CV were 1.8–4.0% and 2.8–5.0%, respectively. ACTH, GH, and IGFBP-3 were measured on chemiluminescent immunometric assay (IMMULITE 2000; Siemens Healthcare Diagnostics, New York, NY, USA). For the ACTH kit, the analytical sensitivity was 5 pg/mL, and intra- and interassay CV were 6.7–9.5% and 6.1–10%, respectively; for the GH kit the analytical sensitivity was 0.01 ng/mL, and intra- and interassay CV were 2.9–4.6% and 4.2–6.6%, respectively. The analytical sensitivity for the IGFBP-3 kit was 100 ng/mL, and the intra- and interassay CV were 4.1–4.8% and 5.2–7.3%, respectively. GHPB (Cusabio-Biotech, Wuhan, China) and IL-6 (Biovender, Heidelberg, Germany) were measured using enzyme-linked immunosorbent assay. The minimum detectable dose of human GHBP was
Pediatrics International (2014) 56, 349–353
doi: 10.1111/ped.12269
Original Article
Evaluation of endocrine function in children admitted to pediatric intensive care unit Banu Küçükemre Aydın,1 Demet Demirkol,2 Firdevs Bas¸,1 Ümit Türkog˘lu,3 Alkın Kumral,3 Metin Karaböcüog˘lu,2 Agop Çıtak2 and Feyza Darendeliler1 1 Department of Pediatrics, Pediatric Endocrinology Unit, 2Department of Pediatrics, Pediatric Intensive Care Unit, and 3 Department of Biochemistry, Faculty of Medicine, Istanbul University, Istanbul, Turkey Abstract
Background: Although studied widely in adulthood, little is known about endocrinological disorders during critical illnesses in childhood. The aims of this study were to define the endocrinological changes in patients admitted to pediatric intensive care unit (PICU) and to identify their effects on prognosis. Methods: Forty patients with a mean age of 5.1 years admitted to PICU were enrolled in the study. Blood samples were taken at admission and at 24 and 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). The severity of the patient’s condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores. Results: PRISM and PELOD scores were significantly higher in non-survivors. Cortisol, ACTH, prolactin, GH, GHBP, IGFBP-3 and IL-6 were not significantly different between the survivors and non-survivors. There was a negative correlation between baseline IGFBP-3 and PRISM scores. A positive correlation was seen between cortisol level at 24 h and PRISM score. On multivariate linear regression analysis, PRISM score was best explained by ACTH and cortisol at 24 h. A positive weak correlation was detected between IL-6 at 24 h and PELOD scores. Conclusions: Although there was no difference between survivors and non-survivors regarding the studied endocrine parameters, there were associations between cortisol, ACTH, IL-6 and IGFBP-3 and risk assessment scores, and, given that these scores correlated with mortality, these parameters might be useful as prognostic factors.
Key words adrenocorticotropic hormone, cortisol, growth hormone, pediatric intensive care, prolactin.
Critical illness is a condition in which patients depend on intensive medical support of vital organ functions in order to survive. Endocrinological and metabolic changes can occur and may affect the prognosis and outcome during this life-threatening situation. Critically ill patients are in a state of extreme physiological stress, with changes in inflammatory pathways, tissue perfusion, and resulting multi-organ dysfunction. These physiological responses, along with interventions at the intensive care unit (ICU), result in a dynamic endocrine response. Basal hormone levels are different in this state due to factors such as changes in secretion, loss of negative feedback, altered target tissue receptor function and impaired enzymatic clearance.1 In critically ill children, disease course and outcome differ from adults.2 Some studies suggest that specific endocrine dysfunction is an age-related phenomenon.2,3 Although studied widely in adulthood, data on endocrinological changes during critical
Correspondence: Banu Küçükemre Aydın, MD, Istanbul University, Istanbul Faculty of Medicine, Istanbul Tip Fakultesi, Pediatrik Endokrinoloji Bilim Dali, Capa 34093, Istanbul, Turkey. Email: [email protected] Received 6 June 2013; revised 24 October 2013; accepted 13 November 2013.
© 2013 The Authors Pediatrics International © 2013 Japan Pediatric Society
illnesses in childhood are scarce. These changes must be investigated in order to construct a treatment strategy. We undertook this prospective study to further expand the knowledge on endocrine derangements in pediatric intensive care unit (PICU) patients. The objectives were to define the type of endocrinological changes appearing in these patients and to identify their effect on prognosis.
Methods Children admitted to the PICU at Istanbul University Hospital within a 15 month period were enrolled in this study. Patients who did not have a prior history of endocrinological disease were considered eligible for recruitment. Forty patients with a mean age of 5.1 years (median, 3.7 years; range, 1 month–15.9 years) were evaluated. Age and gender, and reason for PICU admission were recorded. Patients were divided into five subgroups according to reason for admission. Reasons for admission were cardiopulmonary insufficiency, sepsis, acute change in level of consciousness, liver insufficiency and gastrointestinal bleeding. The severity of the patient’s condition was assessed using pediatric risk of mortality (PRISM) and pediatric logistic organ dysfunction (PELOD) scores.4,5 Mortality and morbidity were recorded. Results were summarized collectively and individually
350
BK Aydın et al.
for the subgroups and compared according to survival status and presence or absence of sequela. Blood samples were taken at admission, at 24 h and at 48 h to measure cortisol, adrenocorticotropic hormone (ACTH), prolactin, growth hormone (GH), GH binding protein (GHBP), insulin-like growth factor-binding protein-3 (IGFBP-3) and interleukin-6 (IL-6). Sera were stored at −80°C until all samples were completed. The samples were run in the same assays using the same kits. Cortisol and prolactin were measured on electrochemiluminescence immunoassay (COBAS; Roche Diagnostics, Mannheim, Germany). For the cortisol kit the lowest limit of detection was 0.018 μg/dL, and intra- and interassay coefficients of variation (CV) were 1.0–1.3% and 1.4–1.6%, respectively. For the prolactin kit the lowest limit of detection was 0.047 ng/mL, and intra- and interassay CV were 1.8–4.0% and 2.8–5.0%, respectively. ACTH, GH, and IGFBP-3 were measured on chemiluminescent immunometric assay (IMMULITE 2000; Siemens Healthcare Diagnostics, New York, NY, USA). For the ACTH kit, the analytical sensitivity was 5 pg/mL, and intra- and interassay CV were 6.7–9.5% and 6.1–10%, respectively; for the GH kit the analytical sensitivity was 0.01 ng/mL, and intra- and interassay CV were 2.9–4.6% and 4.2–6.6%, respectively. The analytical sensitivity for the IGFBP-3 kit was 100 ng/mL, and the intra- and interassay CV were 4.1–4.8% and 5.2–7.3%, respectively. GHPB (Cusabio-Biotech, Wuhan, China) and IL-6 (Biovender, Heidelberg, Germany) were measured using enzyme-linked immunosorbent assay. The minimum detectable dose of human GHBP was
