Diagnosis and treatment of primary central nervous system lymphoma with the primary lesion in the hypothalamus: a case report.

BACKGROUND: Primary central nervous system lymphoma is a rare extra-nodal lymphoma of the central nervous system. Primary central nervous system lymphoma lesions usually appear in the vicinity of the ventricle, and there are few reports of primary central nervous system lymphoma with hypothalamic-pituitary lesions. CASE PRESENTATION: We treated a 56-year-old male with primary central nervous system lymphoma with the primary lesion in the hypothalamus, which was found by magnetic resonance imaging after sudden onset of endocrinological abnormalities. Initially, he was hospitalized to our department for hyponatremia. Endocrinological examination in conjunction with head magnetic resonance imaging and endoscopic biopsy revealed hypothalamic hypopituitarism and tertiary hypoadrenocorticism caused by a rapidly growing, diffuse large B-cell lymphoma in the hypothalamus. Remission of the tumor was achieved by high-dose methotrexate with whole brain radiotherapy, and some of the hormone responses were normalized. CONCLUSIONS: While primary central nervous system lymphoma is rare, it is important to note that hypopituitarism can result and that the endocrinological abnormalities can be partially restored by its remission.

Mechanisms of kidney dysfunction in the cirrhotic patient: Non-hepatorenal acute-on-chronic kidney damage considerations.

Renal dysfunction is a common finding in cirrhotic patients and has a great physiologic, and therefore, prognostic relevance. The combination of liver disease and renal dysfunction can occur as a result of systemic conditions that affect both the liver and the kidney, although primary disorders of the liver complicated by renal dysfunction are much more common. As most of the renal dysfunction scenarios in cirrhotic patients correspond to either prerenal azotemia or hepatorenal syndrome (HRS), physicians tend to conceive renal dysfunction in cirrhotic patients as mainly HRS. However, there are many systemic conditions that may cause both a "baseline" chronic kidney damage and a superimposed kidney dysfunction when this systemic condition worsens. The main aim of this article is to review some of the most important non prerenal non-HRS considerations regarding acute on chronic kidney dysfunction in cirrhotic patients, including renal manifestation of related to non-alcoholic steatohepatitis (NASH) viral hepatitis, the effect of cardiorenal syndrome in cirrhotics and corticosteroid-deficiency associated renal dysfunction.

A retrospective analysis of adrenal crisis in steroid-dependent patients: causes, frequency and outcomes.

BACKGROUND: Adrenal patients have a lifelong dependency on steroid replacement therapy and are vulnerable to sudden death from undertreated adrenal crisis. Urgent treatment with parenteral steroids is needed, often with IV saline for volume repletion. Episodes of adrenal crisis are, for most patients, relatively infrequent and they may not be well prepared to respond. This study explores how patients recall previous episodes of adrenal crisis and their satisfaction with UK emergency medical treatment. METHODS: We invited members of the main UK support groups representing steroid-dependent adrenal patients to complete an online questionnaire identifying the number, causes and location of previous adrenal crises (episodes needing injected steroids and/or IV fluids). Respondents were asked to rate the adequacy of their medical treatment in 2 successive questionnaires, conducted 2013 and 2017-18. RESULTS: Vomiting was the major factor identified as a cause of adrenal crisis, indicated by 80% of respondents. The most common location, at 70%, was the home. Of the 30% away from home, 1 in 3 were overseas or travelling long-distance. Self-treatment played an increasing role in emergency response: in the 5 year interval between questionnaires an increasing number of patients self-injected. By the time of the 2017-18 survey self-injection was the most common method of initial treatment, with less than two-thirds travelling to hospital for follow-up medical treatment. This finding help to explain the higher rate of adrenal crisis identified in patient surveys than in hospital records. Satisfaction with medical care received stayed constant between the 2 surveys despite growing resourcing pressures across the NHS. Two-thirds were happy with the quality of the medical treatment they received for their most recent adrenal emergency; timeliness was the main factor influencing satisfaction. CONCLUSIONS: Around one-third of adrenal patients report sub-optimal treatment at emergency medical departments. Medical staff have a low probability of encountering adrenal crisis and may be unfamiliar with either the urgency of adrenal crisis or the specific treatment response it requires. Comprehensive protocols for emergency medical staff with detailed patient education and training are needed in how to respond to this infrequently encountered - but acutely life-threatening - scenario.

[Functional diagnostics in endocrinology]. / Funktionsdiagnostik in der Endokrinologie.

When investigating many endocrinological diseases, basal laboratory parameters are not sufficient to distinguish between physiological and pathological hormone secretion. Functional diagnostics plays a decisive role in this context. Stimulation and suppression tests are used depending on whether under- or over-function needs to be diagnosed. This review article discusses selected functional tests, each of which plays an important role in current guidelines. Indications and test principles, including their performance, reliability, and limitations, are discussed. Topics covered include the ACTH stimulation test for the diagnosis of adrenal cortex insufficiency and the dexamethasone inhibition test for suspected Cushing's syndrome, as well as functional tests for the diagnosis of primary hyperaldosteronism, pheochromocytoma, acromegaly, growth hormone deficiency, thyroid nodules and suspicion of medullary thyroid carcinoma, insulinoma, and Zollinger-Ellison syndrome. Functional tests that are explicitly not recommended are also addressed.

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study.

INTRODUCTION: Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase. METHODS: We prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 µg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests. RESULTS: Patients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar. CONCLUSIONS: Even though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

A new way of thinking: hydrocortisone in traumatic brain-injured patients.

Data suggest that treatment of critical illness-related corticosteroid insufficiency after traumatic brain injury (TBI) with a stress dose of hydrocortisone may improve the neurological outcome and the mortality rate. The mineralocorticoid properties of hydrocortisone may reduce the rate of hyponatremia and of brain swelling. The exaggerated inflammatory response may cause critical illness-related corticosteroid insufficiency by altering the function of the hypothalamic-pituitary-adrenal axis, and hydrocortisone is able to restore a balanced inflammatory response rather than inducing immunosuppression. Hydrocortisone could also prevent neuronal apoptosis. Considering side effects, corticosteroids are not equal; when a high dose of synthetic corticosteroids seems detrimental, a strategy using a stress dose of hydrocortisone seems attractive. Finally, results from a large multicenter study are needed to close the debate regarding the use of hydrocortisone in TBI patients.

Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats.

INTRODUCTION: The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. METHODS: Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. RESULTS: We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood-brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. CONCLUSIONS: Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus.

Critical illness-related corticosteroid insufficiency in patients with cirrhosis and variceal bleeding.

BACKGROUND & AIMS: Relative adrenal insufficiency (AI) occurs in patients with cirrhosis with sepsis, but not with variceal bleeding. We evaluated adrenal function in cirrhotic patients with and without bleeding. METHODS: Twenty cirrhotic patients with variceal bleeding were evaluated using the short synacthen test (SST) and 10 using the low-dose synacthen test (LDSST) followed by SST. The control group included 60 stable cirrhotic patients, assessed by LDSST (n = 50) or SST (n = 10), and 14 healthy volunteers. AI was diagnosed using SST, based on peak cortisol levels ≤ 18 µg/dL in nonstressed patients or Δmax <9 µg/dL or a total cortisol level <10 µg/dL in stressed patients with variceal bleeding-the current criteria for critical illness-related corticosteroid insufficiency. Using LDSST, diagnosis was based on peak concentrations of cortisol ≤ 18 µg/dL in nonstressed patients and <25 µg/dL (or Δmax <9 µg/dL) in patients with variceal bleeding. We evaluated patients with levels of serum albumin >2.5 g/dL, to indirectly assess cortisol binding. RESULTS: All healthy volunteers had normal results from LDSSTs and SSTs. Patients with variceal bleeding had higher median baseline concentrations of cortisol (15.4 µg/dL) than stable cirrhotic patients (8.7 µg/dL, P = .001) or healthy volunteers (10.1 µg/dL, P = .01). Patients with variceal bleeding had higher median peak concentrations of cortisol than stable cirrhotic patients (SST results of 32.7 vs 21 µg/dL, P = .001; LDSST results of 9.3 vs 8.1 µg/dL; nonsignificant), with no differences in Δmax in either test. These differences were greater with variceal bleeding than in stable cirrhotic patients with AI. Subanalysis of patients with albumin levels >2.5 g/dL did not change these differences. CONCLUSIONS: Cirrhotic patients with variceal bleeding have AI. Despite higher baseline concentrations of serum cortisol and subnormal Δmax values, they did not have adequate responses to stress, and therefore had critical illness-related corticosteroid insufficiency.

Retrospective evaluation of the use of hydrocortisone for treatment of suspected critical illness-related corticosteroid insufficiency (CIRCI) in dogs with septic shock (2010-2017): 47 cases.

OBJECTIVE: To evaluate characteristics of septic shock patients treated with hydrocortisone (HC) due to suspicion of critical illness-related corticosteroid insufficiency (CIRCI) as compared to septic shock patients without suspicion of CIRCI. DESIGN: Retrospective study between February 2010 and October 2017. SETTING: University teaching hospital ICU. ANIMALS: Data were collected for 47 dogs with septic shock. Twenty-one dogs were treated with HC (HC-treated) due to suspicion of CIRCI. Twenty-six dogs did not receive HC (non-HC-treated). INTERVENTIONS: HC was administered either as an intermittent IV bolus or as a constant rate infusion (CRI) to those patients with suspected CIRCI. MEASUREMENTS AND MAIN RESULTS: Significantly higher baseline APPLEfull scores and predicted mortality were detected in the HC-treated patients compared to non-HC-treated patients (0.87 vs 0.44 for predicted mortality, P = 0.039). Patients in the HC-treated group were on more vasopressors and cardiotonics than those in the non-HC-treated group (2.5 vs 1.5, P <0 .001). All patients initially responded to vasopressor administration, with average time to resolution of hypotension being 90 minutes for the HC-treated group compared to 60 minutes for the non-HC-treated group (P = 0.640). However, HC-treated patients took significantly longer to have a sustained resolution (a systolic blood pressure > 90 mm Hg or a mean blood pressure > 65 mm Hg for at least 4 h) of their hypotension after starting vasopressors, as compared to their non-HC-treated counterparts (8.5 vs 4 h, P = 0.001). Three (14.3%) HC-treated patients survived to discharge compared to 9 (34.6%) non-HC-treated patients, but this was not statistically significant. CONCLUSIONS: HC-treated patients had a higher baseline risk of mortality than non-HC-treated patients. There was no significant difference in survival between the HC-treated and non-HC-treated septic shock patients. Further studies are needed to evaluate the use of HC in patients with suspected CIRCI.

Critical illness-related corticosteroid insufficiency in dogs with systemic inflammatory response syndrome: A pilot study in 21 dogs.

Critical illness-related corticosteroid insufficiency (CIRCI) refers to a lack of adequate corticosteroid activity, which occurs in up to 48% of dogs with sepsis. However, data regarding the occurrence of CIRCI in critically-ill dogs are still scarce. This study aimed to assess: (1) the relationship between CIRCI and clinicopathological inflammatory markers, hypotension and mortality; and (2) the impact of low-dose hydrocortisone treatment on survival. Twenty-one dogs diagnosed with systemic inflammatory response syndrome (SIRS) were enrolled in a prospective case-control study. All dogs were initially evaluated for adrenal function with an ACTH stimulation test and dogs with Δcortisol ≤ 3 µg/dL were diagnosed with CIRCI. Mean arterial pressure (MAP), white blood cell (WBC), band neutrophils (bNs), c-reactive protein (CRP), and 28-day mortality rate were assessed. Fourteen dogs were treated with low-dose hydrocortisone. The relationships between CIRCI and MAP, WBC, bN, CRP, basal cortisol and mortality were investigated, as was the association between mortality and hydrocortisone treatment. Ten of 21 (48%) dogs were diagnosed with CIRCI. Increased bNs were associated with the presence of CIRCI (P = 0.0075). CRP was higher in dogs with CIRCI (P = 0.02). Fourteen of 21 (66%) dogs died during the study (6/14 had CIRCI). Basal hypercortisolemia (>5 µg/dL) was associated with increased risk of mortality (P = 0.025). Based on our diagnostic criteria, CIRCI occurs frequently in dogs with SIRS and was associated with increased bNs and increased CRP. In this study, CIRCI and low-dose hydrocortisone treatment were not significantly associated with mortality, but basal hypercortisolemia was associated with increased mortality.

Critical illness-related corticosteroid insufficiency in patients with severe acute biliary pancreatitis: a prospective cohort study.

INTRODUCTION: Gallstones are the most common cause of acute pancreatitis worldwide. Patients with severe acute biliary pancreatitis (SABP) constitute a subgroup of severe acute pancreatitis (SAP) patients in whom systemic inflammation may be triggered and perpetuated by different mechanisms. The aim of this prospective investigation was to examine the adrenal response to corticotropin and the relationship between adrenal function and outcome in patients with SABP. METHODS: Thirty-two patients with SABP were enrolled in this study. A short corticotropin (250 microg) stimulation test (SST) was performed within the first 24 hours of admission to the ICU. Critical illness related corticosteroid insufficiency (CIRCI) was defined as follows: baseline value less than 10 microg/dL, or cortisol response less than 9 microg/dL. RESULTS: CIRCI occurred in 34.4% of patients. The patients with CIRCI were more severely ill as evidenced by higher APACHE II and SOFA scores and numbers of organ system dysfunction on the day of SST. The in-hospital mortality for the entire group was 21.9%. The CIRCI group had a higher hospital mortality rate compared to those with normal adrenal function (45.5% vs. 9.5%, P = 0.032). The hospital survivors had a higher cortisol response to corticotropin (17.4 (8.3-27.1) vs. 7.2 (1.7-12) microg/dL, P = 0.019). The cortisol response to corticotropin inversely correlated with SOFA score and the number of organ dysfunction on the day of SST. The rates of pancreatic necrosis and bacteremia were significantly higher in the CIRCI group (100% vs 42.9%, P = 0.002; 81.8% vs 23.8%, P = 0.003, respectively). CONCLUSIONS: CIRCI is common in patients with SABP. It is associated with bacteremia, multiple organ dysfunction and increased mortality.

Steroid dysregulation and stomatodynia (burning mouth syndrome).

Stomatodynia ( burning mouth syndrome) is characterized by a spontaneous, continuous burning pain felt in the oral mucosa typically of anxiodepressive menopausal women. Because there is no obvious organic cause, it is considered a nonspecific pain. This Focus Article proposes a hypothesis based on the following pathophysiological cascade: chronic anxiety or post traumatic stress leads to a dysregulation of the adrenal production of steroids. One consequence is a decreased or modified production of some major precursors for the neuroactive steroid synthesis occurring in the skin, mucosa, and nervous system. At menopause, the drastic fall of the other main precursor supply , the gonadal steroids, leads to a brisk alteration of the production of neuroactive steroids. This results in neurodegenerative alterations of small nerves fibers of the oral mucosa and /or some brain areas involved in oral somatic sensations. These neuropathic changes become irreversible and precipitate the burning pain, dysgeusia, and xerostomia associated with stomatodynia, which all involve thin nerve fibers.

Kidney transplantation with corticosteroid-free maintenance immunosuppression: a single center analysis of graft and patient survivals.

The purpose of this study was to assess the impact of a corticosteroid-free maintenance immunosuppression on graft survival in kidney transplantation. We analyzed 79 patients who were transplanted between June 1, 2006 and May 31, 2007. We excluded hyperimmunized patients, second transplantations, living donors, and black recipients. Patients underwent induction with thymoglobulin or basiliximab, followed by treatment with mycophenolate mofetil (MMF), tacrolimus, and methylprednisolone. On the 5th day, the patients were divided into 2 groups: group A (n = 45) discontinued steroid therapy; group B (n = 34) continued prednisone therapy. We performed a comparative analysis of incidence of delayed graft function (DGF), acute rejection episodes (ARE), renal function at 6 and 12 months, graft and patient survivals, causes of graft loss, and mortality. The 2 groups were similar for donor, recipient, and graft characteristics. The incidences of DGF were 8.9% in group A and 14.7% in group B; those for ARE were 2.3% in group A and 13.8% in group B (P = .077). The mean serum creatinine levels at 6 and 12 months were similar. There were 8 graft losses: 3 in group A (3 deaths with functioning grafts) and 5 in group B (1 death, 3 vascular causes, 1 kidney nonfunction). The 4 deaths were due to infection (n = 3) or neoplasia (n = 1). Graft survivals at 1 year were 98% in group A and 85% in group B, and patient survivals were 98% and 97%, respectively. An immunosuppressive regimen using antibody induction and steroid-free treatment proved to be effective in low-risk patients.

Successful treatment with hydrocortisone for heat stroke with critical illness-related corticosteroid insufficiency: transitional changes in serum cytokine and cortisol concentrations.

A 37-year-old man was transferred to our emergency center because of heat stroke with circulatory shock. Despite aggressive body cooling, massive intravenous transfusion, and supply of inotropic agents, shock was persistent. To evaluate adrenal function, an adrenocorticotropic hormone stimulation test was conducted and the results indicated that he had critical illness-related corticosteroid insufficiency (CIRCI) as a result of adrenal insufficiency. Continuous hydorocortisone administration was started and he recovered from shock within a few hours. He was discharged on the thirty-seventh hospital day. Serum cortisol and cytokine concentrations were initially high and the cytokines decreased subsequent to hydrocortisone administration. It is speculated that CIRCI is an exacerbating factor in heat stroke, and hydrocortisone may be a potential therapeutic approach in such patients.

[Corticosteroid insufficiency in the critically ill. Pathomechanisms and recommendations for diagnosis and treatment]. / Kortikosteroidinsuffizienz bei kritisch Kranken. Pathomechanismen und Empfehlungen zur Diagnose und Behandlung.

Critically ill patients with severe systemic inflammation can develop critical illness-related corticosteroid insufficiency (CIRCI), which is associated with a poor outcome. A task force of the American College of Critical Care Medicine compiled recommendations for diagnosis and treatment of this clinical entity thereby focusing on patients with septic shock and acute respiratory distress syndrome (ARDS). The results of large scale multi-centre trials gave partially conflicting results arguing against the broad use of corticosteroids in stress doses. However, the task force recommended treatment with stress-dose corticosteroids in patients with septic shock who respond poorly to fluid resuscitation and vasopressor therapy and in patients with early ARDS (<14 days after onset). The dose of corticosteroids should be reduced in a step-wise manner. Corticosteroids at stress doses are currently under investigation in other target populations of critically ill patients potentially suffering from CIRCI. Preliminary data suggest that patients with vasodilatory shock after cardiac surgery and patients with liver cirrhosis and sepsis can benefit from corticosteroids. Critical illness-related corticosteroid insufficiency can also occur in patients with trauma, traumatic brain injury, acute pancreatitis and burn injuries, but data from clinical trials on these target groups are insufficient at present. The therapeutic use of corticosteroids in stress doses reduces the incidence of post-traumatic stress disorder (PTSD) after intensive care treatment.

Critical Roles of Endogenous Glucocorticoids for Disease Tolerance in Malaria.

During malaria, the hypothalamic-pituitary-adrenal (HPA) axis is activated and glucocorticoid (GC) levels are increased, but their essential roles have been largely overlooked. GCs are decisive for systemic regulation of vital processes such as immune responses, vascular function, and metabolism, which are crucial in malaria. Here, we introduce GCs in general, followed by their versatile roles for disease tolerance in malaria. A complementary comparison is provided with their role in sepsis. Finally, potential translational implications are considered. The failed clinical trials of dexamethasone against cerebral malaria in the past have diminished the interest in GCs in malaria. However, the issue of relative corticosteroid insufficiency has barely been explored in malaria patients, but may hold promise for a better understanding and treatment of specific malaria complications.

Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine.

OBJECTIVE: To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients. PARTICIPANTS: A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from the membership of the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. In addition, international experts in endocrinology were invited to participate. DESIGN/METHODS: The task force members reviewed published literature and provided expert opinion from which the consensus was derived. The consensus statements were developed using a modified Delphi methodology. The strength of each recommendation was quantified using the Modified GRADE system, which classifies recommendations as strong (grade 1) or weak (grade 2) and the quality of evidence as high (grade A), moderate (grade B), or low (grade C) based on factors that include the study design, the consistency of the results, and the directness of the evidence. RESULTS: The task force coined the term critical illness-related corticosteroid insufficiency to describe the dysfunction of the hypothalamic-pituitary-adrenal axis that occurs during critical illness. Critical illness-related corticosteroid insufficiency is caused by adrenal insufficiency together with tissue corticosteroid resistance and is characterized by an exaggerated and protracted proinflammatory response. Critical illness-related corticosteroid insufficiency should be suspected in hypotensive patients who have responded poorly to fluids and vasopressor agents, particularly in the setting of sepsis. At this time, the diagnosis of tissue corticosteroid resistance remains problematic. Adrenal insufficiency in critically ill patients is best made by a delta total serum cortisol of < 9 microg/dL after adrenocorticotrophic hormone (250 microg) administration or a random total cortisol of < 10 microg/dL. The benefit of treatment with glucocorticoids at this time seems to be limited to patients with vasopressor-dependent septic shock and patients with early severe acute respiratory distress syndrome (PaO2/FiO2 of < 200 and within 14 days of onset). The adrenocorticotrophic hormone stimulation test should not be used to identify those patients with septic shock or acute respiratory distress syndrome who should receive glucocorticoids. Hydrocortisone in a dose of 200 mg/day in four divided doses or as a continuous infusion in a dose of 240 mg/day (10 mg/hr) for > or = 7 days is recommended for septic shock. Methylprednisolone in a dose of 1 mg x kg(-1) x day(-1) for > or = 14 days is recommended in patients with severe early acute respiratory distress syndrome. Glucocorticoids should be weaned and not stopped abruptly. Reinstitution of treatment should be considered with recurrence of signs of sepsis, hypotension, or worsening oxygenation. Dexamethasone is not recommended to treat critical illness-related corticosteroid insufficiency. The role of glucocorticoids in the management of patients with community-acquired pneumonia, liver failure, pancreatitis, those undergoing cardiac surgery, and other groups of critically ill patients requires further investigation. CONCLUSION: Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.

Corticosteroids, a review.

Recent studies have shown a strong correlation between the nervous, endocrine and immune systems. Knowledge of how these systems interact is important for understanding the pathogenesis of autoimmune diseases such as rheumatoid arthritis (RA) and to open new therapeutic perspectives. New theories suggest that in RA there is an inappropriate response of the hypothalamic-pituitary-adrenal axis to the increase in pro-inflammatory cytokines, resulting in a corticosteroid (CS) insufficiency state. While recent observations have questioned the positive effect of CS on the progression of joint damage, efficacious new drugs such as anti-TNF have attracted attention to agents without the side effects of CS. Cartilage oligomeric matrix protein, a new biohumoral marker, has recently led to a re-evaluation of CS in RA therapy.

Critical illness-related corticosteroid insufficiency (CIRCI): a narrative review from a Multispecialty Task Force of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM).

OBJECTIVE: To provide a narrative review of the latest concepts and understanding of the pathophysiology of critical illness-related corticosteroid insufficiency (CIRCI). PARTICIPANTS: A multispecialty task force of international experts in critical care medicine and endocrinology and members of the Society of Critical Care Medicine (SCCM) and the European Society of Intensive Care Medicine (ESICM). DATA SOURCES: Medline, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews. RESULTS: Three major pathophysiologic events were considered to constitute CIRCI: dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, altered cortisol metabolism, and tissue resistance to glucocorticoids. The dysregulation of the HPA axis is complex, involving multidirectional crosstalk between the CRH/ACTH pathways, autonomic nervous system, vasopressinergic system, and immune system. Recent studies have demonstrated that plasma clearance of cortisol is markedly reduced during critical illness, explained by suppressed expression and activity of the primary cortisol-metabolizing enzymes in the liver and kidney. Despite the elevated cortisol levels during critical illness, tissue resistance to glucocorticoids is believed to occur due to insufficient glucocorticoid alpha-mediated anti-inflammatory activity. CONCLUSIONS: Novel insights into the pathophysiology of CIRCI add to the limitations of the current diagnostic tools to identify at-risk patients and may also impact how corticosteroids are used in patients with CIRCI.