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Chen X, Chai Y, Wang SB, Wang JC, Yue SY, Jiang RC, Zhang JN. Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury. Neural Regen Res 2020; 15:1259-1265. [PMID: 31960811 PMCID: PMC7047797 DOI: 10.4103/1673-5374.272611] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency. Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury, but few studies have examined this occurrence. A multicenter, prospective, cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China, and the critical illness-related corticosteroid insufficiency incidence, critical-illness-related corticosteroid insufficiency-related risk factors, complications, and 28-day mortality among these patients was recorded. Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10 μg/dL (275.9 nM) on post-injury day 4 or when serum cortisol was insufficiently suppressed (less than 50%) during a dexamethasone suppression test on post-injury day 5. The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6% of patients with mild injury, 22.5% of patients with moderate injury, and 52.2% of patients with severe injury. Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury. Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions, diffuse axonal injury, brain herniation, and hypotension. Differences in the incidence of hospital-acquired pneumonia, gastrointestinal bleeding, and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. Hypotension, brain-injury severity, and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency. These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis. The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury, especially those with hypotension, hemorrhagic cerebral contusions, diffuse axonal injury, and brain herniation. Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency. This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University, China in December 2011 (approval No. 201189).
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Affiliation(s)
- Xin Chen
- Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, China
| | - Yan Chai
- Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
| | - Shao-Bo Wang
- Department of Neurosurgery, Ordos Central Hospital, Ordos, Inner Mongolia Autonomous Region, China
| | - Jia-Chong Wang
- Department of Neurosurgery, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Changsha, Hunan Province, China
| | - Shu-Yuan Yue
- Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, China
| | - Rong-Cai Jiang
- Department of Neurosurgery, General Hospital of Tianjin Medical University, Tianjin, China
| | - Jian-Ning Zhang
- Tianjin Neurological Institute; Key Laboratory of Post-trauma Neuro-repair and Regeneration in Central Nervous System, Ministry of Education; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China
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Iyer P, Harrington B, Fadrowski JJ, Sibinga E, Amankwah EK. Correlation between Cosyntropin Stimulation Study and Disease Severity in Children with Fluid- and Catecholamine-Refractory Shock in the Pediatric and Cardiovascular Intensive Care Unit. Horm Res Paediatr 2018; 89:31-37. [PMID: 29151100 DOI: 10.1159/000484561] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Accepted: 10/24/2017] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND The cosyntropin stimulation study (CSS) measures the patient's ability to adequately mount a cortisol response. Clinically, CSS results may not be used to guide hydrocortisone use. The objective of this study was to examine how the CSS results are associated with clinical parameters, mortality/disease severity, and use of glucocorticoids in pediatric patients with catecholamine- and fluid-resistant shock. METHODS This was a retrospective cohort study of patients who had a CSS during 2009-2014 in the intensive care unit at a children's hospital. Data collected included clinical variables, mortality, biochemical studies, and glucocorticoid use. PRISM III scores were used to determine the association between CSS results and disease severity. Adequate response to cosyntropin was defined as peak cortisol of 18 µg/dL or higher. RESULTS Of the 76 patients that underwent CSS, 68 (89%) had an adequate response to cosyntropin. There was a positive correlation between peak cortisol and PRISM III score (r = 0.45, r2 = 0.2). Glucocorticoid was administered in 52/76 (68%) despite several patients with normal CSS results. CONCLUSIONS Sicker patients were more likely to have an adequate response to CSS. Clinically, glucocorticoid supplementation was not based on CSS results. Further prospective studies are needed to elucidate if CSS is a valuable clinical tool.
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Affiliation(s)
- Pallavi Iyer
- University of Alabama at Birmingham, Birmingham, Alabama, USA
| | - Brittany Harrington
- Garden City Hospital, Michigan State University COM, Garden City, Michigan, USA
| | | | | | - Ernest K Amankwah
- Johns Hopkins All Children's Hospital, Saint Petersburg, Florida, USA
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Uçar A, Baş F, Saka N. Diagnosis and management of pediatric adrenal insufficiency. World J Pediatr 2016; 12:261-274. [PMID: 27059746 DOI: 10.1007/s12519-016-0018-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 02/24/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. DATA SOURCES We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. RESULTS Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. CONCLUSIONS Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.
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Affiliation(s)
- Ahmet Uçar
- Growth-Development and Pediatric Endocrine Unit, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey.
| | - Firdevs Baş
- Growth-Development and Pediatric Endocrine Unit, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey
| | - Nurçin Saka
- Growth-Development and Pediatric Endocrine Unit, Istanbul School of Medicine, Istanbul University, Istanbul, Turkey
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Chiriac Ş, Stanciu C, Negru R, Trifan A. ASSESSMENT OF ADRENOCORTICAL DYSFUNCTION IN PATIENTS WITH STABLE LIVER CIRRHOSIS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2016; 12:262-267. [PMID: 31149099 PMCID: PMC6535276 DOI: 10.4183/aeb.2016.262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
INTRODUCTION Relative adrenal insufficiency (RAI) is common in the setting of critical illness as well as in hemodynamically instable cirrhotic patients with sepsis. Several studies have also shown that RAI is frequent in patients with stable cirrhosis without sepsis. The aim of this study was to prospectively assess the incidence of RAI in patients with stable cirrhosis. PATIENTS AND METHODS Forty-seven patients with hemodynamically stable liver cirrhosis without sepsis were prospectively included. RAI, assessed by using low dose-short Synacthen test (LD-SST), was defined as either a basal total cortisol concentration below 3.6 µg/dL or a peak total serum cortisol ≤ 16 µg/dL at 30 min after stimulation. RESULTS RAI was present in 10 (21.3%) of 47 cirrhotic patients. Peak cortisol level was negatively correlated with the severity of cirrhosis evaluated by Child-Turcotte-Pugh (CTP) (r=-0.46; P=0.001) and Model for End-Stage Liver Disease (MELD) (r=-0.51; P=0.001) scores. The frequency of RAI increased from CTP-A (10%) to CTP-B (30%) to CTP-C (60%). CONCLUSION RAI diagnosed by LD-SST is frequent in patients with stable cirrhosis and is related to the severity of liver disease. Further studies are needed to define clinical importance of RAI in stable cirrhotic patients.
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Affiliation(s)
- Ş. Chiriac
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
| | - C. Stanciu
- “St. Spiridon” Emergency Hospital - Institute of Gastroenterology and Hepatology, Iaşi, Romania
| | - R. Negru
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
| | - A. Trifan
- “Grigore T. Popa” University of Medicine and Pharmacy, Iaşi, Romania
- “St. Spiridon” Emergency Hospital - Institute of Gastroenterology and Hepatology, Iaşi, Romania
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Karagiannis AKA, Nakouti T, Pipili C, Cholongitas E. Adrenal insufficiency in patients with decompensated cirrhosis. World J Hepatol 2015; 7:1112-1124. [PMID: 26052400 PMCID: PMC4450188 DOI: 10.4254/wjh.v7.i8.1112] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2014] [Revised: 01/12/2015] [Accepted: 02/11/2015] [Indexed: 02/06/2023] Open
Abstract
Adrenal reserve depletion and overstimulation of the hypothalamus-pituitary-adrenal (HPA) axis are causes for adrenal insufficiency (AI) in critically ill individuals. Cirrhosis is a predisposing condition for AI in cirrhotics as well. Both stable cirrhotics and liver transplant patients (early and later after transplantation) have been reported to present AI. The mechanisms leading to reduced cortisol production in cirrhotics are the combination of low cholesterol levels (the primary source of cortisol), the increased cytokines production that overstimulate and exhaust HPA axis and the destruction of adrenal glands due to coagulopathy. AI has been recorded in 10%-82% cirrhotics depending on the test used to evaluate adrenal function and in 9%-83% stable cirrhotics. The similarity of those proportions support the assumption that AI is an endogenous characteristic of liver disease. However, the lack of a gold standard method for AI assessment and the limitation of precise thresholds in cirrhotics make difficult the recording of the real prevalence of AI. This review aims to summarize the present data over AI in stable, critically ill cirrhotics and liver transplant recipients. Moreover, it provides information about the current knowledge in the used diagnostic tools and the possible effectiveness of corticosteroids administration in critically ill cirrhotics with AI.
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Abstract
Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids, with or without deficiency also in mineralocorticoids and adrenal androgens. It is a life-threatening disorder that can result from primary adrenal failure or secondary adrenal disease due to impairment of the hypothalamic-pituitary axis. Prompt diagnosis and management are essential. The clinical manifestations of primary adrenal insufficiency result from deficiency of all adrenocortical hormones, but they can also include signs of other concurrent autoimmune conditions. In secondary or tertiary adrenal insufficiency, the clinical picture results from glucocorticoid deficiency only, but manifestations of the primary pathological disorder can also be present. The diagnostic investigation, although well established, can be challenging, especially in patients with secondary or tertiary adrenal insufficiency. We summarise knowledge at this time on the epidemiology, causal mechanisms, pathophysiology, clinical manifestations, diagnosis, and management of this disorder.
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Affiliation(s)
- Evangelia Charmandari
- Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece; Division of Endocrinology and Metabolism, Clinical Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
| | - Nicolas C Nicolaides
- Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece; Division of Endocrinology and Metabolism, Clinical Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
| | - George P Chrousos
- Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, University of Athens Medical School, Aghia Sophia Children's Hospital, Athens, Greece; Division of Endocrinology and Metabolism, Clinical Research Center, Biomedical Research Foundation of the Academy of Athens, Athens, Greece
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A preliminary investigation into adrenal responsiveness and outcomes in patients with cardiogenic shock after acute myocardial infarction. J Crit Care 2014; 29:470.e1-6. [PMID: 24656116 DOI: 10.1016/j.jcrc.2014.01.020] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2013] [Revised: 01/20/2014] [Accepted: 01/26/2014] [Indexed: 12/13/2022]
Abstract
PURPOSE This study investigated the significance of baseline cortisol levels and adrenal response to corticotropin in shocked patients after acute myocardial infarction (AMI). METHODS A short corticotropin stimulation test was performed in 35 patients with cardiogenic shock after AMI by intravenously injecting of 250 μg of tetracosactrin (Synacthen). Blood samples were obtained at baseline (T0) before and at 30 (T30) and 60 (T60) minutes after the test to determine plasma total cortisol (TC) and free cortisol concentrations. The main outcome measure was in-hospital mortality and its association with T0 TC and maximum response to corticotropin (maximum difference [Δ max] in cortisol levels between T0 and the highest value between T30 and T60). RESULTS The in-hospital mortality was 37%, and the median time to death was 4 days (interquartile range, 3-9 days). There was some evidence of an increased mortality in patients with T0 TC concentrations greater than 34 μg/dL (P=.07). Maximum difference by itself was not an independent predictor of death. Patients with a T0 TC 34 μg/dL or less and Δ max greater than 9 μg/dL appeared to have the most favorable survival (91%) when compared with the other 2 groups: T0 34 μg/dL or less and Δ max 9 μg/dL or less or T0 34 μg/dL or higher and Δ max greater than 9 μg/dL (75%; P=.8) and T0 greater than 34 μg/dL and Δ max 9 μg/dL or less (60%; P=.02). Corticosteroid therapy was associated with an increased mortality (P=.03). There was a strong correlation between plasma TC and free cortisol (r=0.85). CONCLUSIONS A high baseline plasma TC was associated with a trend toward increased mortality in patients with cardiogenic shock post-AMI. Patients with lower baseline TC, but with an inducible adrenal response, appeared to have a survival benefit. A prognostic system based on basal TC and Δ max similar to that described in septic shock appears feasible in this cohort. Corticosteroid therapy was associated with adverse outcomes. These findings require further validation in larger studies.
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Hebbar KB, Stockwell JA, Fortenberry JD. Clinical effects of adding fludrocortisone to a hydrocortisone-based shock protocol in hypotensive critically ill children. Intensive Care Med 2011; 37:518-24. [PMID: 21152900 DOI: 10.1007/s00134-010-2090-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2010] [Accepted: 11/08/2010] [Indexed: 10/18/2022]
Abstract
BACKGROUND Adult studies evaluating corticosteroids have found varied efficacy. One study showing mortality benefit utilized fludrocortisone (FLU) and hydrocortisone (HC) (Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 288:862-871, 2002). Use of FLU in children has not been described. We developed a protocol using HC for systemic inflammatory response syndrome (SIRS) and shock with optional addition of FLU. HYPOTHESIS Addition of FLU to a HC-based steroid protocol is associated with decreased vasopressor duration without adverse effects in hypotensive children with SIRS. METHODS Retrospective review of low-dose HC and FLU supplementation in children with SIRS and fluid refractory shock. Patients receiving FLU in addition to HC were compared with patients receiving HC alone. RESULTS Ninety-seven children with SIRS and shock received steroids. Sixty of 97 (62%) received FLU in addition to HC. Seventy-three children required dopamine (DA) infusion, and 56 received norepinephrine (NE). Overall mortality was 7/97 (7%), with 5/7 (71%) nonsurvivors receiving HC + FLU. Fifty of 97 (52%) children with SIRS met definition for sepsis. Septic children who received HC + FLU required NE for significantly shorter duration than those receiving HC alone (p = 0.011). Nineteen of 60 HC + FLU patients (32%) developed nonsymptomatic hypokalemia. Hypokalemia was significantly more common in HC + FLU patients compared with those receiving HC alone (p = 0.05). CONCLUSIONS Overall, addition of FLU in children with SIRS was not associated with decreased vasopressor duration or vasopressor score. However, HC + FLU was associated with shorter duration of NE support in the septic subgroup. Hypokalemia was a frequent adverse finding with HC + FLU (p = 0.05). Use of FLU should be considered in further studies evaluating the role of steroids in refractory pediatric septic shock.
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Affiliation(s)
- Kiran B Hebbar
- Division of Critical Care, Department of Pediatrics, Emory University School of Medicine and Children's Healthcare of Atlanta at Egleston, Atlanta, GA 30322, USA.
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