Medicine › Endocrinology, Diabetes and Metabolism

Adrenal Hormones and Disorders

Works Count: 51288

Wikipedia

Description

This cluster of papers focuses on the diagnosis and management of adrenal insufficiency, particularly in the context of septic shock and autoimmune polyendocrine syndrome. It covers topics such as corticosteroid therapy, hydrocortisone treatment, AIRE gene mutations, cortisol response, and the impact on the hypothalamic-pituitary-adrenal axis. The research also delves into glucocorticoid replacement, autoimmune disorders, and endocrine dysfunction.

Keywords

Adrenal Insufficiency; Corticosteroid Therapy; Septic Shock; Autoimmune Polyendocrine Syndrome; Hydrocortisone Treatment; Glucocorticoid Replacement; AIRE Gene Mutations; Cortisol Response; Endocrine Disorders; Hypothalamic-Pituitary-Adrenal Axis Dysfunction

Risk of Infectious Complications in Patients Taking Glucocorticosteroids

1989-11-01

Andreas E. Stuck , C. E. Minder , Felix J. Frey

The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients … The association between corticosteroid therapy and subsequent infections was calculated by pooling data from 71 controlled clinical trials. The overall rate of infectious complications was 12.7% in the 2,111 patients randomly allocated to systemic corticosteroids and 8.0% in the 2,087 controls (relative risk [RR], 1.6; 95% confidence interval [CI], 1.3–1.9; P < .001). The risk of infection was particularly high in patients with neurologic diseases (RR, 2.8; 95% CI, 1.9–4.3; P< .001) and less pronounced in patients with intestinal (RR, 1.4; 95% CI, 1.1–1.7; P = .02), hepatic (RR, 1.4; 95% CI, 0.9–2.3; P = .25), and renal (RR>1; P = .03) diseases. The rate was not increased in patients given a daily dose of <10 mg or a cumulative dose of <700 mg of prednisone. With increasing doses the rate of occurrence of infectious complications increased in patients given corticosteroids as well as in patients given placebo, a finding suggesting that not only the corticosteroid but also the underlying disease state account for the steroid-associated infectious complications observed in clinical practice.

View PDF Chat

The Pathophysiologic Roles of Interleukin-6 in Human Disease

1998-01-15

Dimitris A. Papanicolaou

Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is … Interleukin-6, an inflammatory cytokine, is characterized by pleiotropy and redundancy of action. Apart from its hematologic, immune, and hepatic effects, it has many endocrine and metabolic actions. Specifically, it is a potent stimulator of the hypothalamic-pituitary-adrenal axis and is under the tonic negative control of glucocorticoids. It acutely stimulates the secretion of growth hormone, inhibits thyroid-stimulating hormone secretion, and decreases serum lipid concentrations. Furthermore, it is secreted during stress and is positively controlled by catecholamines. Administration of interleukin-6 results in fever, anorexia, and fatigue. Elevated levels of circulating interleukin-6 have been seen in the steroid withdrawal syndrome and in the severe inflammatory, infectious, and traumatic states potentially associated with the inappropriate secretion of vasopressin. Levels of circulating interleukin-6 are also elevated in several inflammatory diseases, such as rheumatoid arthritis. Interleukin-6 is negatively controlled by estrogens and androgens, and it plays a central role in the pathogenesis of the osteoporosis seen in conditions characterized by increased bone resorption, such as sex-steroid deficiency and hyperparathyroidism. Overproduction of interleukin-6 may contribute to illness during aging and chronic stress. Finally, administration of recombinant human interleukin-6 may serve as a stimulation test for the integrity of the hypothalamic-pituitary-adrenal axis.

The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

2008-03-12

Lynnette K. Nieman , Beverly M. K. Biller , James W. Findling +4 more

The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of … The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome.The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration.Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments.After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

View PDF Chat

Aire regulates negative selection of organ-specific T cells

2003-03-03

Adrian Liston , Sylvie Lesage , Judith Wilson +2 more

Regulation of the Immune System by Sex Steroids*

1984-07-01

Charles J. Grossman

IN THE PAST 10 years there has been a significant increase in studies relating to the function of the immune system. The recent popularity of research in this area is … IN THE PAST 10 years there has been a significant increase in studies relating to the function of the immune system. The recent popularity of research in this area is due in part to the awareness by the medical and scientific community of the importance of immune function in the maintenance of a disease-free homeostasis, to technological advances in the field of immunological research, and to the increased availability of funds for investigation in this area. From the rapidly expanding literature in this field it has become increasingly apparent that the immune system interacts with most, if not all, of the body systems. One of the most intriguing of these interrelationships is that which occurs between the immune and reproductive systems and involves interactions of pituitary hormones, gonadal steroid hormones and thymic hormones. Because of the complexity of this area the present review will concentrate on only one aspect of the interaction between the two systems, namely the effects of gonadal steroids on immune function.

The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights

2010-04-15

Agnes E. Coutinho , Karen E. Chapman

Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and … Since the discovery of glucocorticoids in the 1940s and the recognition of their anti-inflammatory effects, they have been amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. However, their clinical efficacy is compromised by the metabolic effects of long-term treatment, which include osteoporosis, hypertension, dyslipidaemia and insulin resistance/type 2 diabetes mellitus. In recent years, a great deal of effort has been invested in identifying compounds that separate the beneficial anti-inflammatory effects from the adverse metabolic effects of glucocorticoids, with limited effect. It is clear that for these efforts to be effective, a greater understanding is required of the mechanisms by which glucocorticoids exert their anti-inflammatory and immunosuppressive actions. Recent research is shedding new light on some of these mechanisms and has produced some surprising new findings. Some of these recent developments are reviewed here.

View PDF Chat

Positional cloning of the APECED gene

1997-12-01

Kentaro Nagamine , Pärt Peterson , Hamish S. Scott +7 more

Reversal of late septic shock with supraphysiologic doses of hydrocortisone

1998-04-01

Pierre‐Édouard Bollaert , Claire Charpentier , Bruno Lévy +3 more

Objectives Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, … Objectives Preliminary studies have suggested that low doses of corticosteroids might rapidly improve hemodynamics in late septic shock treated with catecholamines. We examined the effect of hydrocortisone on shock reversal, hemodynamics, and survival in this particular setting. Design Prospective, randomized, double-blind, placebo-controlled study. Setting Two intensive care units of a University hospital. Patients Forty-one patients with septic shock requiring catecholamine for >48 hrs. Interventions Patients were randomly assigned either hydrocortisone (100 mg iv three times daily for 5 days) or matching placebo. Measurements and Main Results Reversal of shock was defined by a stable systolic arterial pressure (>90 mm Hg) for >or=to24 hrs without catecholamine or fluid infusion. Of the 22 hydrocortisone-treated patients and 19 placebo-treated patients, 15 (68%) and 4 (21%) achieved 7-day shock reversal, respectively, a difference of 47% (95% confidence interval 17% to 77%; p=.007). Serial invasive hemodynamic measurements for 5 days did not show significant differences between both groups. At 28-day follow-up, reversal of shock was higher in the hydrocortisone group (p=.005). Crude 28-day mortality was 7 (32%) of 22 treated patients and 12 (63%) of 19 placebo patients, a difference of 31% (95% confidence interval 1% to 61%; p=.091). Shock reversal within 7 days after the onset of corticosteroid therapy was a very strong predictor of survival. There were no significant differences in outcome in responders and nonresponders to a short corticotropin test. The respective rates of gastrointestinal bleeding and secondary infections did not differ between both groups. Conclusions Administration of modest doses of hydrocortisone in the setting of pressor-dependent septic shock for a mean of >96 hrs resulted in a significant improvement in hemodynamics and a beneficial effect on survival. These beneficial effects do not appear related to adrenocortical insufficiency. (Crit Care Med 1998;26:645-650)

Side Effects of Corticosteroid Therapy

2001-10-01

Alan L. Buchman

Background Corticosteroids have been used for the treatment of inflammatory bowel disease since the late 1940s. Upwards of 80% of patients may respond acutely to treatment with these medications, although … Background Corticosteroids have been used for the treatment of inflammatory bowel disease since the late 1940s. Upwards of 80% of patients may respond acutely to treatment with these medications, although 20% or more may be refractory and others become dependent on corticosteroid use to suppress disease activity. Side effects in the acute situation are relatively minor, although significant side effects (e.g., psychosis) have been encountered; the long-term use of corticosteroids is more problematic. This creates a milieu for the potential for serious and irreversible problems. These side effects are discussed in detail. The side effects from corticosteroids emulate from exogenous hypercortisolism, which is similar to the clinical syndrome of Cushing's disease. Study PubMed search for years 1966–2000, author's personal manuscript/abstract files, and citations of known references. Conclusion Short-term corticosteroid use is associated with generally mild side effects, including cutaneous effects, electrolyte abnormalities, hypertension, hyperglycemia, pancreatitis, hematologic, immunologic, and neuropsychologic effects, although occasionally, clinically significant side effects may occur. Long-term corticosteroid use may be associated with more serious sequale, including osteoporosis, aseptic joint necrosis, adrenal insufficiency, gastrointestinal, hepatic, and ophthalmologic effects, hyperlipidemia, growth suppression, and possible congenital malformations.

Salivary Cortisol: A Better Measure of Adrenal Cortical Function than Serum Cortisol

1983-11-01

R. F. W. VINING , R McGinley , J. Maksvytis +1 more

Salivary Cortisol concentration was found to be directly proportional to the serum unbound Cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin (CBG). The … Salivary Cortisol concentration was found to be directly proportional to the serum unbound Cortisol concentration both in normal men and women and in women with elevated cortisol-binding globulin (CBG). The correlation was excellent in dynamic tests of adrenal function (dexamethasone suppression, ACTH stimulation), in normals and patients with adrenal insufficiency, in tests of circadian variation and randomly collected samples. Women in the third trimester of normal pregnancy exhibited elevated salivary Cortisol throughout the day. The relationship between salivary and serum total Cortisol concentration was markedly non-linear with a more rapid increase in salivary concentration once the serum CBG was saturated. The rate of equilibrium of Cortisol between blood and saliva was very fast, being much less than 5 minutes. These data, combined with a simple, stress-free, non-invasive collection procedure, lead us to suggest that salivary Cortisol is a more appropriate measure for the clinical assessment of adrenocortical function than is serum Cortisol.

Williams Textbook of Endocrinology

2009-09-15

Sirimon Reutrakul

ISBN: 978-1-4160-2911-3, 1911 pages, Hard Cover. Edition: 11th. Editors: Henry M. Kronenberg, MD; Shlomo Melmed, MD, FRCP; Kenneth S. Polonsky, MD; P. Reed Larsen, MD, FACP, FRCP. Specialties: Endocrinology/Metabolic Disease, … ISBN: 978-1-4160-2911-3, 1911 pages, Hard Cover. Edition: 11th. Editors: Henry M. Kronenberg, MD; Shlomo Melmed, MD, FRCP; Kenneth S. Polonsky, MD; P. Reed Larsen, MD, FACP, FRCP. Specialties: Endocrinology/Metabolic Disease, General Medicine. Publisher: Elsevier/Saunders. List Price: $179.00 DESCRIPTION: This book covers all area of endocrinology, starting with fundamental principles in hormones and hormone action as well as laboratory techniques for recognition of endocrine disorders. PURPOSE: To serve as a condensed and authoritative discussion of the clinical management of endocrinopathies on the basis of the information obtained from chemical, physiological, genetic, epidemiologic investigation, and clinical trial data. AUDIENCE: This is a comprehensive resource for practicing endocrinologists as well as clinical and basic researchers. Fellows in training and internists will find useful fundamental information that will aid understanding of basic but important concepts in endocrinology. FEATURES: This book describes thyroid, adrenal, and reproductive disorders as well as their clinical management. The chapter on type 2 diabetes mellitus is superbly written by leading researchers in both basic and clinical sciences. A new chapter covers neuroendocrine control of appetite and body weight. ASSESSMENT: Since the 2003 edition was published, many discoveries have been made in the field of endocrinology. The exceptional quality of this book makes it an essential reference in the field. Leading authorities provide a blend of scientific insight and clinical know-how. A new full-color, user-friendly format makes use of this text a snap. Full text, on-line access allows contents to be searched rapidly from any computer. An access code is given for the publisher Web site and additional resources. RATING: ★★★★★ Reviewed by: Sirimon Reutrakul, MD (University of Chicago Medical Center, Chicago, IL)

Glucocorticosteroid Therapy: Mechanisms of Action and Clinical Considerations

1976-03-01

Anthony S. Fauci

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal … The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

Systemic Adverse Effects of Inhaled Corticosteroid Therapy

1999-05-10

Brian J. Lipworth

<h3>Objective</h3> To appraise the data on systemic adverse effects of inhaled corticosteroids. <h3>Methods</h3> A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS … <h3>Objective</h3> To appraise the data on systemic adverse effects of inhaled corticosteroids. <h3>Methods</h3> A computerized database search from January 1, 1966, through July 31, 1998, using MEDLINE, EMBASE, and BIDS and using appropriate indexed terms. Reports dealing with the systemic effects of inhaled corticosteroids on adrenal gland, growth, bone, skin, and eye, and reports on pharmacology and pharmacokinetics were reviewed where appropriate. Studies were included that contained evaluable data on systemic effects in healthy volunteers as well as in asthmatic children and adults. A statistical meta-analysis using regression was performed for parameters of adrenal suppression in 27 studies. <h3>Results</h3> Marked adrenal suppression occurs with high doses of inhaled corticosteroid above 1.5 mg/d (0.75 mg/d for fluticasone propionate), although there is a considerable degree of interindividual susceptibility. Meta-analysis showed significantly greater potency for dose-related adrenal suppression with fluticasone compared with beclomethasone dipropionate, budesonide, or triamcinolone acetonide, whereas prednisolone and fluticasone propionate were approximately equivalent on a 10:1-mg basis. Inhaled corticosteroids in doses above 1.5 mg/d (0.75 mg/d for fluticasone propionate) may be associated with a significant reduction in bone density, although the risk for osteoporosis may be obviated by postmenopausal estrogen replacement therapy. Although medium-term growth studies showed suppressive effects with 400-µg/d beclomethasone dipropionate, there was no evidence to support any significant effects on final adult height. Long-term, high-dose inhaled corticosteroid exposure increases the risk for posterior subcapsular cataracts, and, to a much lesser degree, the risk for ocular hypertension and glaucoma. Skin bruising is most likely to occur with high-dose exposure, which correlates with the degree of adrenal suppression. <h3>Conclusions</h3> All inhaled corticosteroids exhibit dose-related systemic adverse effects, although these are less than with a comparable dose of oral corticosteroids. Meta-analysis shows that fluticasone propionate exhibits greater dose-related systemic bioactivity compared with other available inhaled corticosteroids, particularly at doses above 0.8 mg/d. The long-term systemic burden will be minimized by always trying to achieve the lowest possible maintenance dose that is associated with optimal asthmatic control and quality of life.

An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains

1997-12-01

Johanna Aaltonen , Petra Björses , Jaakko Perheentupa +7 more

Pituitary Expression of CTLA-4 Mediates Hypophysitis Secondary to Administration of CTLA-4 Blocking Antibody

2014-04-02

Shintaro Iwama , Alessandra De Remigis , Margaret K. Callahan +3 more

CTLA-4 blocking antibody induces secondary hypophysitis by binding to CTLA-4 antigen and initiating a type II hypersensitivity reaction. CTLA-4 blocking antibody induces secondary hypophysitis by binding to CTLA-4 antigen and initiating a type II hypersensitivity reaction.

Autoimmune Polyendocrine Syndromes

2004-05-12

George S. Eisenbarth , Peter A. Gottlieb

This review considers the pathogenesis, scope, and treatment of autoimmune polyendocrine syndromes. Although some of the component disorders such as thyroid autoimmunity and celiac disease are common, others such as … This review considers the pathogenesis, scope, and treatment of autoimmune polyendocrine syndromes. Although some of the component disorders such as thyroid autoimmunity and celiac disease are common, others such as Addison's disease and myasthenia gravis are rare.

Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production.

1982-11-01

David S. Snyder , Emil R. Unanue

Corticosteroids have profound effects on functions of the macrophage associated with antigen presentation to T cells. The drugs inhibited the expression of surface I-region-associated (Ia) antigens by peritoneal macrophages both … Corticosteroids have profound effects on functions of the macrophage associated with antigen presentation to T cells. The drugs inhibited the expression of surface I-region-associated (Ia) antigens by peritoneal macrophages both in vitro and in vivo, reduced the production of IL 1, and inhibited antigen presentation for T cell proliferation by macrophages. The doses of hydrocortisone and prednisolone that inhibited by 50% Ia expression in cultured macrophages ranged around 2 to 5 x 10(-8) M. These results could explain one mechanism by which corticosteroids suppress the induction of immune responses.

View PDF Chat

Hydrocortisone Therapy for Patients with Septic Shock

2008-01-09

Charles L. Sprung , Djillali Annane , Didier Keh +7 more

Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose … Hydrocortisone is widely used in patients with septic shock even though a survival benefit has been reported only in patients who remained hypotensive after fluid and vasopressor resuscitation and whose plasma cortisol levels did not rise appropriately after the administration of corticotropin.In this multicenter, randomized, double-blind, placebo-controlled trial, we assigned 251 patients to receive 50 mg of intravenous hydrocortisone and 248 patients to receive placebo every 6 hours for 5 days; the dose was then tapered during a 6-day period. At 28 days, the primary outcome was death among patients who did not have a response to a corticotropin test.Of the 499 patients in the study, 233 (46.7%) did not have a response to corticotropin (125 in the hydrocortisone group and 108 in the placebo group). At 28 days, there was no significant difference in mortality between patients in the two study groups who did not have a response to corticotropin (39.2% in the hydrocortisone group and 36.1% in the placebo group, P=0.69) or between those who had a response to corticotropin (28.8% in the hydrocortisone group and 28.7% in the placebo group, P=1.00). At 28 days, 86 of 251 patients in the hydrocortisone group (34.3%) and 78 of 248 patients in the placebo group (31.5%) had died (P=0.51). In the hydrocortisone group, shock was reversed more quickly than in the placebo group. However, there were more episodes of superinfection, including new sepsis and septic shock.Hydrocortisone did not improve survival or reversal of shock in patients with septic shock, either overall or in patients who did not have a response to corticotropin, although hydrocortisone hastened reversal of shock in patients in whom shock was reversed. (ClinicalTrials.gov number, NCT00147004.)

Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I

2010-02-01

Anne Puel , Rainer Döffinger , Angels Natividad +7 more

Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high … Most patients with autoimmune polyendocrine syndrome type I (APS-I) display chronic mucocutaneous candidiasis (CMC). We hypothesized that this CMC might result from autoimmunity to interleukin (IL)-17 cytokines. We found high titers of autoantibodies (auto-Abs) against IL-17A, IL-17F, and/or IL-22 in the sera of all 33 patients tested, as detected by multiplex particle-based flow cytometry. The auto-Abs against IL-17A, IL-17F, and IL-22 were specific in the five patients tested, as shown by Western blotting. The auto-Abs against IL-17A were neutralizing in the only patient tested, as shown by bioassays of IL-17A activity. None of the 37 healthy controls and none of the 103 patients with other autoimmune disorders tested had such auto-Abs. None of the patients with APS-I had auto-Abs against cytokines previously shown to cause other well-defined clinical syndromes in other patients (IL-6, interferon [IFN]-gamma, or granulocyte/macrophage colony-stimulating factor) or against other cytokines (IL-1beta, IL-10, IL-12, IL-18, IL-21, IL-23, IL-26, IFN-beta, tumor necrosis factor [alpha], or transforming growth factor beta). These findings suggest that auto-Abs against IL-17A, IL-17F, and IL-22 may cause CMC in patients with APS-I.

View PDF Chat

Pharmacokinetics and Pharmacodynamics of Systemically Administered Glucocorticoids

2005-01-01

David Czock , Frieder Keller , Franz Maximilian Rasche +1 more

A simple fluorimetric method for the estimation of free 11-hydroxycorticoids in human plasma

1962-07-01

D Mattingly

A simple fluorimetric method is described for measuring free 11-hydroxycorticoids in human plasma. Only 2 ml. of plasma is required for each estimation and the fluorescence is read in a … A simple fluorimetric method is described for measuring free 11-hydroxycorticoids in human plasma. Only 2 ml. of plasma is required for each estimation and the fluorescence is read in a standard direct reading fluorimeter. Six estimations can be completed in one and a half hours. It thus compares favourably with the methods in current use for estimating urinary steroids, and has the added advantage of not being dependent on the accurate collection of 24-hour urine samples.

View PDF Chat

Measurements of Serum Free Cortisol in Critically Ill Patients

2004-04-14

Amir H. Hamrahian , T. Salewa Oseni , Baha M. Arafah

Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of … Because more than 90 percent of circulating cortisol in human serum is protein-bound, changes in the binding proteins can alter measured serum total cortisol concentrations without influencing free concentrations of this hormone. We investigated the effect of decreased amounts of cortisol-binding proteins on serum total and free cortisol concentrations during critical illness, when glucocorticoid secretion is maximally stimulated.Base-line serum total cortisol, cosyntropin-stimulated serum total cortisol, aldosterone, and free cortisol concentrations were measured in 66 critically ill patients and 33 healthy volunteers in groups that were similar with regard to sex and age. Of the 66 patients, 36 had hypoproteinemia (albumin concentration, 2.5 g per deciliter or less), and 30 had near-normal serum albumin concentrations (above 2.5 g per deciliter).Base-line and cosyntropin-stimulated serum total cortisol concentrations were lower in the patients with hypoproteinemia than in those with near-normal serum albumin concentrations (P<0.001). However, the mean (+/-SD) base-line serum free cortisol concentrations were similar in the two groups of patients (5.1+/-4.1 and 5.2+/-3.5 microg per deciliter [140.7+/-113.1 and 143.5+/-96.6 nmol per liter]) and were several times higher than the values in controls (0.6+/-0.3 microg per deciliter [16.6+/-8.3 nmol per liter], P<0.001 for both comparisons). Cosyntropin-stimulated serum total cortisol concentrations were subnormal (18.5 microg per deciliter [510.4 nmol per liter] or less) in 14 of the patients, all of whom had hypoproteinemia. In all 66 patients, including these 14 who had hypoproteinemia, the base-line and cosyntropin-stimulated serum free cortisol concentrations were high-normal or elevated.During critical illness, glucocorticoid secretion markedly increases, but the increase is not discernible when only the serum total cortisol concentration is measured. In this study, nearly 40 percent of critically ill patients with hypoproteinemia had subnormal serum total cortisol concentrations, even though their adrenal function was normal. Measuring serum free cortisol concentrations in critically ill patients with hypoproteinemia may help prevent the unnecessary use of glucocorticoid therapy.

View PDF Chat

Autoimmune Adrenal Insufficiency and Autoimmune Polyendocrine Syndromes: Autoantibodies, Autoantigens, and Their Applicability in Diagnosis and Disease Prediction

2002-06-01

Corrado Betterle , Chiara Dal Prà , Franco Mantero +1 more

Abstract Recent progress in the understanding of autoimmune adrenal disease, including a detailed analysis of a group of patients with Addison’s disease (AD), has been reviewed. Criteria for defining an … Abstract Recent progress in the understanding of autoimmune adrenal disease, including a detailed analysis of a group of patients with Addison’s disease (AD), has been reviewed. Criteria for defining an autoimmune disease and the main features of autoimmune AD (history, prevalence, etiology, histopathology, clinical and laboratory findings, cell-mediated andhumoral immunity, autoantigens and their autoepitopes, genetics, animal models, associated autoimmune diseases, pathogenesis, natural history, therapy) have been described. Furthermore, the autoimmune polyglandular syndromes (APS) associated with AD (revised classification, animal models, genetics, natural history) have been discussed. Of Italian patients with primary AD (n = 317), 83% had autoimmune AD. At the onset, all patients with autoimmune AD (100%) had detectable adrenal cortex and/or steroid 21-hydroxylase autoantibodies. In the course of natural history of autoimmune AD, the presence of adrenal cortex and/or steroid 21-hydroxylase autoantibodies identified patients at risk to develop AD. Different risks of progression to clinical AD were found in children and adults, and three stages of subclinical hypoadrenalism have been defined. Normal or atrophic adrenal glands have been demonstrated by imaging in patients with clinical or subclinical AD. Autoimmune AD presented in four forms: as APS type 1 (13% of the patients), APS type 2 (41%), APS type 4 (5%), and isolated AD (41%). There were differences in genetics, age at onset, prevalence of adrenal cortex/21-hydroxylase autoantibodies, and associated autoimmune diseases in these groups. “Incomplete” forms of APS have been identified demonstrating that APS are more prevalent than previously reported. A varied prevalence of hypergonadotropic hypogonadism in patients with AD and value of steroid-producing cells autoantibodies reactive with steroid 17α-hydroxylase or P450 side-chain cleavage enzyme as markers of this disease has been discussed. In addition, the prevalence, characteristic autoantigens, and autoantibodies of minor autoimmune diseases associated with AD have been described. Imaging of adrenal glands, genetic tests, and biochemical analysis have been shown to contribute to early and correct diagnosis of primary non-autoimmune AD in the cases of hypoadrenalism with undetectable adrenal autoantibodies. An original flow chart for the diagnosis of AD has been proposed.

Corticosteroid Insufficiency in Acutely Ill Patients

2003-02-20

Mark S. Cooper , Paul M. Stewart

Recent studies report benefits from corticosteroid treatment in patients with septic shock. This review summarizes the physiology of the corticosteroid response in acute illness. The authors present an updated, practical … Recent studies report benefits from corticosteroid treatment in patients with septic shock. This review summarizes the physiology of the corticosteroid response in acute illness. The authors present an updated, practical approach to the diagnosis and treatment of hypoadrenalism in acutely ill patients. Supplemental corticosteroid treatment may be beneficial in many critical illnesses.

Physiology and pharmacology of corticotropin-releasing factor.

1991-12-01

Michael J. Owens , Charles B. Nemeroff

A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy

2013-08-15

Dora Liu , Alexandra Ahmet , Leanne M. Ward +6 more

Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular … Systemic corticosteroids play an integral role in the management of many inflammatory and immunologic conditions, but these agents are also associated with serious risks. Osteoporosis, adrenal suppression, hyperglycemia, dyslipidemia, cardiovascular disease, Cushing's syndrome, psychiatric disturbances and immunosuppression are among the more serious side effects noted with systemic corticosteroid therapy, particularly when used at high doses for prolonged periods. This comprehensive article reviews these adverse events and provides practical recommendations for their prevention and management based on both current literature and the clinical experience of the authors.

View PDF Chat

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

2008-05-29

Paul E. Marik , Stephen M. Pastores , Djillali Annane +7 more

To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.A multidisciplinary, multispecialty task force of experts in critical care medicine was convened from … To develop consensus statements for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients.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.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.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.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.

Immunologic and Hemodynamic Effects of “Low-Dose” Hydrocortisone in Septic Shock

2003-02-14

Didier Keh , T Boehnke , Steffen Weber‐Carstens +7 more

Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between … Within the last few years, increasing evidence of relative adrenal insufficiency in septic shock evoked a reassessment of hydrocortisone therapy. To evaluate the effects of hydrocortisone on the balance between proinflammatory and antiinflammation, 40 patients with septic shock were randomized in a double-blind crossover study to receive either the first 100 mg of hydrocortisone as a loading dose and 10 mg per hour until Day 3 (n = 20) or placebo (n = 20), followed by the opposite medication until Day 6. Hydrocortisone infusion induced an increase of mean arterial pressure, systemic vascular resistance, and a decline of heart rate, cardiac index, and norepinephrine requirement. A reduction of plasma nitrite/nitrate indicated inhibition of nitric oxide formation and correlated with a reduction of vasopressor support. The inflammatory response (interleukin-6 and interleukin-8), endothelial (soluble E-selectin) and neutrophil activation (expression of CD11b, CD64), and antiinflammatory response (soluble tumor necrosis factor receptors I and II and interleukin-10) were attenuated. In peripheral blood monocytes, human leukocyte antigen-DR expression was only slightly depressed, whereas in vitro phagocytosis and the monocyte-activating cytokine interleukin-12 increased. Hydrocortisone withdrawal induced hemodynamic and immunologic rebound effects. In conclusion, hydrocortisone therapy restored hemodynamic stability and differentially modulated the immunologic response to stress in a way of antiinflammation rather than immunosuppression.

Antiinflammatory Action of Glucocorticoids — New Mechanisms for Old Drugs

2005-10-20

Turk Rhen , John A. Cidlowski

Glucocorticoids are among the most common therapeutic agents used in medical practice, yet their mechanisms of action are only partly understood. This review summarizes our understanding of how glucocorticoids inhibit … Glucocorticoids are among the most common therapeutic agents used in medical practice, yet their mechanisms of action are only partly understood. This review summarizes our understanding of how glucocorticoids inhibit inflammation and give rise to side effects.

A 3-Level Prognostic Classification in Septic Shock Based on Cortisol Levels and Cortisol Response to Corticotropin

2000-02-23

Djillali Annane

The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress. The relationship between its activation and patient outcome is not known.To evaluate the prognostic value of cortisol … The hypothalamic-pituitary-adrenal axis is a major determinant of the host response to stress. The relationship between its activation and patient outcome is not known.To evaluate the prognostic value of cortisol levels and a short corticotropin stimulation test in patients with septic shock.Prospective inception cohort study conducted between October 1991 and September 1995 in 2 teaching hospital adult intensive care units in France.A total of 189 consecutive patients who met clinical criteria for septic shock.A short corticotropin stimulation test was performed in all patients by intravenously injecting 0.25 mg of tetracosactrin; blood samples were taken immediately before the test (T0) and 30 (T30) and 60 (T60) minutes afterward.Twenty-eight-day mortality as a function of variables collected at the onset of septic shock, including cortisol levels before the corticotropin test and the cortisol response to corticotropin (delta max, defined as the difference between T0 and the highest value between T30 and T60).The 28-day mortality was 58% (95% confidence interval [CI], 51%-65%) and median time to death was 17 days (95% CI, 14-27 days). In multivariate analysis, independent predictors of death (P < or = .001 for all) were McCabe score greater than 0, organ system failure score greater than 2, arterial lactate level greater than 2.8 mmol/L, ratio of PaO2 to fraction of inspired oxygen no more than 160 mm Hg, cortisol level at T0 greater than 34 microg/dL and delta max no more than 9 microg/dL. Three groups of patient prognoses were identified: good (cortisol level at T0 < or = 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 26%), intermediate (cortisol level at T0 34 microg/dL and delta max < or = 9 microg/dL or cortisol level at T0 > 34 microg/dL and delta max > 9 microg/dL; 28-day mortality rate, 67%), and poor (cortisol level at T0 > 34 microg/dL and delta max < or = 9 microg/dL; 28-day mortality rate, 82%).Our data suggest that a short corticotropin test has a good prognostic value and could be helpful in identifying patients with septic shock at high risk for death.

The Effect of In Vivo Hydrocortisone on Subpopulations of Human Lymphocytes

1974-01-01

Anthony S. Fauci , David C. Dale

This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg … This study was designed to determine the effect of in vivo hydrocortisone on subpopulations of lymphoid cells in normal humans. Subjects received a single intravenous dose of either 100 mg or 400 mg of hydrocortisone, and blood was drawn at hourly intervals for 6 h, and then again at 10 and 24 h after injection. Profound decreases in absolute numbers of circulating lymphocytes and monocytes occurred at 4-6 h after both 100 mg and 400 mg of hydrocortisone. Counts returned to normal by 24 h. The relative proportion of circulating thymus-derived lymphocytes as measured by the sheep red blood cell rosette assay decreased maximally by 4 h and returned to base line 24 h after hydrocortisone. There was a selective depletion of functional subpopulations of lymphocytes as represented by differential effects on in vitro stimulation with various mitogens and antigens. Phytohaemagglutinin response was relatively unaffected, while responses to concanavalin A were significantly diminished. Responses to pokeweed mitogen were unaffected by 100 mg of hydrocortisone, but greatly diminished by 400 mg of hydrocortisone. In vitro responses to the antigens streptokinase-streptodornase and tetanus toxoid were markedly diminished by in vivo hydrocortisone. Reconstitution of monocyte-depleted cultures with autologous monocytes partially corrected the diminished response to antigens. This transient selective depletion of monocytes and subsets of human lymphocytes by a single dose of hydrocortisone is most compatible with a redistribution of these cells out of the circulation into other body compartments.

View PDF Chat

Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines

2010-02-01

Kai Kisand , Anette S. B. Wolff , Katarina Trebušak Podkrajšek +7 more

Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis … Chronic mucocutaneous candidiasis (CMC) is frequently associated with T cell immunodeficiencies. Specifically, the proinflammatory IL-17A–producing Th17 subset is implicated in protection against fungi at epithelial surfaces. In autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED, or autoimmune polyendocrine syndrome 1), CMC is often the first sign, but the underlying immunodeficiency is a long-standing puzzle. In contrast, the subsequent endocrine features are clearly autoimmune, resulting from defects in thymic self-tolerance induction caused by mutations in the autoimmune regulator (AIRE). We report severely reduced IL-17F and IL-22 responses to both Candida albicans antigens and polyclonal stimulation in APECED patients with CMC. Surprisingly, these reductions are strongly associated with neutralizing autoantibodies to IL-17F and IL-22, whereas responses were normal and autoantibodies infrequent in APECED patients without CMC. Our multicenter survey revealed neutralizing autoantibodies against IL-17A (41%), IL-17F (75%), and/ or IL-22 (91%) in &gt;150 APECED patients, especially those with CMC. We independently found autoantibodies against these Th17-produced cytokines in rare thymoma patients with CMC. The autoantibodies preceded the CMC in all informative cases. We conclude that IL-22 and IL-17F are key natural defenders against CMC and that the immunodeficiency underlying CMC in both patient groups has an autoimmune basis.

View PDF Chat

Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein

2002-11-14

Mark S. Anderson , Emily S. Venanzi , Ludger Klein +7 more

Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates … Humans expressing a defective form of the transcription factor AIRE (autoimmune regulator) develop multiorgan autoimmune disease. We used aire- deficient mice to test the hypothesis that this transcription factor regulates autoimmunity by promoting the ectopic expression of peripheral tissue- restricted antigens in medullary epithelial cells of the thymus. This hypothesis proved correct. The mutant animals exhibited a defined profile of autoimmune diseases that depended on the absence of aire in stromal cells of the thymus. Aire-deficient thymic medullary epithelial cells showed a specific reduction in ectopic transcription of genes encoding peripheral antigens. These findings highlight the importance of thymically imposed "central" tolerance in controlling autoimmunity.

Glucocorticoids and the Th1/Th2 Balance

2004-06-01

Ilia J. Elenkov

A bstract : Evidence accumulated over the last 5‐10 years indicates that glucocorticoids (GCs) inhibit the production of interleukin (IL)‐12, interferon (IFN)‐γ, IFN‐α, and tumor necrosis factor (TNF)‐α by antigen‐presenting … A bstract : Evidence accumulated over the last 5‐10 years indicates that glucocorticoids (GCs) inhibit the production of interleukin (IL)‐12, interferon (IFN)‐γ, IFN‐α, and tumor necrosis factor (TNF)‐α by antigen‐presenting cells (APCs) and T helper (Th)1 cells, but upregulate the production of IL‐4, IL‐10, and IL‐13 by Th2 cells. Through this mechanism increased levels of GCs may systemically cause a selective suppression of the Th1‐cellular immunity axis, and a shift toward Th2‐mediated humoral immunity, rather than generalized immunosuppression. During an immune response and inflammation, the activation of the stress system, and thus increased levels of systemic GCs through induction of a Th2 shift, may actually protect the organism from systemic “overshooting” with Th1/pro‐inflammatory cytokines and other products of activated macrophages with tissue‐damaging potential. However, conditions associated with significant changes of GCs levels, such as acute or chronic stress or cessation of chronic stress, severe exercise, and pregnancy and postpartum, through modulation of the Th1/Th2 balance may affect the susceptibility to or the course of infections as well as autoimmune and atopic/allergic diseases.

View PDF Chat

Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline

2016-01-13

Stefan R. Bornstein , Bruno Allolio , Wiebke Arlt +7 more

This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight … This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 μg) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15–25 mg/d) or cortisone acetate replacement (20–35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (∼8 mg/m2/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.

View PDF Chat

Long-term side effects of glucocorticoids

2016-01-20

Merih Oray , Khawla Abu Samra , Nazanin Ebrahimiadib +2 more

Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may … Glucocorticoids represent the standard therapy for reducing inflammation and immune activation in various diseases. However, as with any potent medication, they are not without side effects. Glucocorticoid-associated side effects may involve most major organ systems. Musculoskeletal, gastrointestinal, cardiovascular, endocrine, neuropsychiatric, dermatologic, ocular, and immunologic side effects are all possible.This article analyzes English-language literature and provides an update on the most recent literature regarding side effects of systemic glucocorticoid treatment.The risk/benefit ratio of glucocorticoid therapy can be improved by proper use. Careful monitoring and using appropriate preventive strategies can potentially minimize side effects.

Current concepts of the immunological function of the thymus.

1967-07-01

J. F. A. P. Miller , David Osoba

View PDF Chat

The Effect of a Hormone of the Adrenal Cortex (17-hydroxy-11-dehydrocorticosterone: Compound E) and of Pituitary Adrenocorticotropic Hormone on Rheumatoid Arthritis

1949-04-01

Philip S. Hench , Edward C. Kendall

The Hypothalamic–Pituitary–Adrenal Axis and Immune-Mediated Inflammation

1995-05-18

George P. Chrousos

Celsus described four of the five cardinal signs of inflammation 2000 years ago, and Eustachio discovered the adrenal glands almost 500 years ago, but not until 1936 did Selye note … Celsus described four of the five cardinal signs of inflammation 2000 years ago, and Eustachio discovered the adrenal glands almost 500 years ago, but not until 1936 did Selye note that in rats exposed to stressors, the adrenal glands were enlarged, and the thymus and lymph nodes shrunken.13 Cortisone, the active principle of the adrenal glands, was isolated by Kendall and Reichstein in the late 1940s and shown to suppress immune organs. These scientists, along with Hench, received the Nobel Prize in Physiology and Medicine, after Hench and colleagues showed that cortisone could ameliorate rheumatoid arthritis.4,5 In recent . . .

Clinical Variation of Autoimmune Polyendocrinopathy–Candidiasis–Ectodermal Dystrophy (APECED) in a Series of 68 Patients

1990-06-28

Pekka Ahonen , S Myllärniemi , Ilkka Sipilä +1 more

To define the clinical picture and course of the autosomal recessive disease called autoimmune polyendocrinopathy—candidiasis—ectodermal dystrophy (APECED), we report data from our 10-month to 31-year follow-up of 68 patients from … To define the clinical picture and course of the autosomal recessive disease called autoimmune polyendocrinopathy—candidiasis—ectodermal dystrophy (APECED), we report data from our 10-month to 31-year follow-up of 68 patients from 54 families, now 10 months to 53 years of age.

View PDF Chat

Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline

2016-10-13

Maria Fleseriu , Ibrahim A. Hashim , Niki Karavitaki +4 more

To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults.The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American … To formulate clinical practice guidelines for hormonal replacement in hypopituitarism in adults.The participants include an Endocrine Society-appointed Task Force of six experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology co-sponsored this guideline.The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies.One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the Pituitary Society, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines.Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.

View PDF Chat

Effect of Treatment With Low Doses of Hydrocortisone and Fludrocortisone on Mortality in Patients With Septic Shock

2002-08-21

Djillali Annane

EVERE SEPSIS REMAINS AN IMPORtant cause of death, accounting for 9.3% of all deaths in the United States in 1995. 1 If our understanding of the mechanisms of host response … EVERE SEPSIS REMAINS AN IMPORtant cause of death, accounting for 9.3% of all deaths in the United States in 1995. 1 If our understanding of the mechanisms of host response to stress has strongly progressed during the last 2 decades, 2 the various drugs developed for specific targets of the cytokine cascade have failed to improve patient survival. 3,4orticosteroids were the first antiinflammatory drugs tested in randomized trials.At high doses during short courses, they did not induce favorable effects. 5,6However, the observation that severe sepsis may be associated with relative adrenal insufficiency 7,8 or systemic inflammation-induced glucocorticoid receptor resistance 9 prompted renewed interest of a replacement therapy

Immune regulation by glucocorticoids

2017-02-13

Derek W. Cain , John A. Cidlowski

Hydrocortisone plus Fludrocortisone for Adults with Septic Shock

2018-02-28

Djillali Annane , Alain Renault , Christian Brun‐Buisson +7 more

Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa … Septic shock is characterized by dysregulation of the host response to infection, with circulatory, cellular, and metabolic abnormalities. We hypothesized that therapy with hydrocortisone plus fludrocortisone or with drotrecogin alfa (activated), which can modulate the host response, would improve the clinical outcomes of patients with septic shock.

View PDF Chat

[The endocrine system].

1961-10-01

Arias Vallejo E

Adrenal insufficiency

2003-05-01

Wiebke Arlt , Bruno Allolio

Adrenal Insufficiency

1996-10-17

W. Oelkers

The hypothalamic–pituitary–adrenal axis has an important role in the body's ability to cope with stresses such as infections, hypotension, and surgery. The hypothalamus is subject to regulatory influences from other … The hypothalamic–pituitary–adrenal axis has an important role in the body's ability to cope with stresses such as infections, hypotension, and surgery. The hypothalamus is subject to regulatory influences from other parts of the brain, especially the limbic system. The hypothalamic hormones corticotropin-releasing hormone and arginine vasopressin are important stimulants of corticotropin secretion by the anterior pituitary. In this gland, the action of the hypothalamic hormones is amplified so that a much larger number of corticotropin molecules is secreted. Similarly, in the adrenal cortex the action of corticotropin is amplified; a plasma corticotropin concentration of approximately 25 pg per milliliter (5.5 . . .

Clinical Variability in Congenital Adrenal Hyperplasia: A Distinct Subgroup with A Low Glucocorticoid Dose Requirement

2025-06-23

Ala Üstyol , Erica A. Eugster | Hormone Research in Paediatrics

Some children with classic congenital adrenal hyperplasia (CAH) achieve excellent control on very low glucocorticoid doses. We aimed to characterize these patients and assess the timing of their low-dose requirements. … Some children with classic congenital adrenal hyperplasia (CAH) achieve excellent control on very low glucocorticoid doses. We aimed to characterize these patients and assess the timing of their low-dose requirements. We reviewed charts of patients with salt-wasting CAH due to 21-hydroxylase deficiency, defining low-dose glucocorticoids as <10 mg/m²/d. Demographic and growth data were compared with a matched group on standard doses. Among 154 patients with CAH, 14 (9%) required low-dose glucocorticoid therapy (<10 mg/m²/d), including 8 boys (57%) and 6 girls (43%). The average age at treatment initiation was 2.1 years, comparable to a matched group of 23 patients (48% boys). The low-dose group received 8.8 ± 1.2 mg/m²/d versus 14.9 ± 3.9 mg/m²/d in the matched group (P < 0.001), with similar fludrocortisone doses (0.1 ± 0.05 mg). No differences were observed in weight, height, or height velocity. Of the 14 patients on low-dose treatment, 3 experienced an increase in their glucocorticoid dose requirement above 10 mg/m2/d at ages 10.3, 10.8, and 8.5 years after being on 6.3 -9.8 mg/m2/d for 6.4-8.5 years. The remaining 11 patients are currently on 5.89-10 mg/m2/d with a duration on low-dose therapy ranging from 0.48 to 8.65 years. Our findings highlight a subgroup of patients with 21-hydroxylase deficiency who achieve good control on low glucocorticoid doses from early childhood. The factors underlying this and the transient need for low doses in some remain unclear.

Ketamine

2025-06-21

| Reactions Weekly

CD137 might be a pivotal regulator of Th1/Th17-driven autoimmunity and B-cell hyperactivity in hyperthyroidism

2025-06-19

Shuangshuang Li , Kunyi Li , Jinying Li +2 more | Molecular Immunology

Female fertility and pregnancy in autoimmune Addison’s disease – a mini review

2025-06-18

Liam O’Murchadha , Agnieszka Pazderska | Frontiers in Endocrinology

Autoimmune Addison’s Disease (AAD) is by far the most common cause of primary adrenal insufficiency in developed countries, occurring more commonly in women compared with men. The condition is associated … Autoimmune Addison’s Disease (AAD) is by far the most common cause of primary adrenal insufficiency in developed countries, occurring more commonly in women compared with men. The condition is associated with a spectrum of disorders affecting fertility and reproductive health. Premature ovarian insufficiency (POI) is a clinical condition defined by cessation of menstrual cycles and menopausal range gonadotrophins before the age of 40 years. This occurs with a prevalence of 1-2% in the general population, but has been estimated at 6-10% for women with AAD. One registry study demonstrated that one-third of those with AAD who develop POI, do so before the age of thirty. The onset of POI precedes or is contemporaneous with the diagnosis of AAD in the majority. It has also been demonstrated that women with AAD are more likely to use hormone replacement therapy. The pathophysiology of POI in this cohort is thought to be primarily through autoimmune mediated inflammation of the ovarian theca cells. In particular, cross-reacting autoantibodies to steroid-producing cells (StCA) have been identified which are present in AAD and POI. That said, when women with POI are excluded, fertility remains significantly reduced. Impaired adrenal androgenesis and resulting sex-hormone deficiency have also been implicated in subfertility in AAD. These lead to suboptimal follicular development. This, in turn, may also affect libido. Despite physiological glucocorticoid replacement therapy, patients with AAD consistently report reduced quality of life compared to matched controls. These factors may affect fecundity and likelihood of conception. Other autoimmune conditions such as hypothyroidism and type 1 diabetes occur with increased prevalence in those with AAD. These conditions have been shown to independently affect reproductive health. This review focuses on the current understanding of the factors and mechanisms impacting fertility in women with autoimmune Addison’s disease.

Thyroxine Reveals Addison’s Disease: A Case Report

2025-06-18

Vasiliki Rengina Tsinopoulou , Savvas Kolanis , Dimitra Katsarou +2 more | Cureus

Síndrome de Addison agudo con crisis adrenal infradiagnosticada en el servicio de emergencias: reporte de caso clínico

2025-06-18

Grace Vanessa Bayas Huilcapi , Julio Daniel Salame Atiencia , Dayanara Pilar Briones Villamar +2 more | Arandu-UTIC.

El síndrome de Addison agudo constituye una emergencia endocrina infrecuente, pero con mortalidad superior al 8 % cuando el diagnóstico se retrasa. Presentamos el caso de un varón de 49 … El síndrome de Addison agudo constituye una emergencia endocrina infrecuente, pero con mortalidad superior al 8 % cuando el diagnóstico se retrasa. Presentamos el caso de un varón de 49 años atendido en el servicio de emergencias de una clínica de Guayaquil (abril 2025) con astenia súbita, hipotensión refractaria, dolor abdominal inespecífico y vómitos. El manejo inicial se orientó a un shock distributivo de probable origen séptico; sin embargo, la ausencia de fiebre, la hiponatremia (118 mmol/L), la hipercalemia leve y la hipoglucemia persistente motivaron la revisión diagnóstica. Conforme a la guía conjunta ESE/Endocrine Society 2023, se obtuvieron cortisol basal de 38 nmol/L y ACTH de 1150 pg/mL antes de administrar 100 mg de hidrocortisona i.v., logrando respuesta hemodinámica en 60 min. La TAC abdominal descartó hemorragia suprarrenal. A las 24 h se inició esquema de estrés con hidrocortisona 50 mg/6 h y fludrocortisona 0,1 mg/día, con transición a terapia oral al alta. Este reporte subraya la necesidad de mantener un alto índice de sospecha ante cuadros de shock que no responden a la reanimación convencional y demuestra que la aplicación temprana de protocolos actualizados reduce complicaciones y estancia hospitalaria. La educación del personal de emergencias sobre signos prodrómicos y el uso de pruebas rápidas de cortisol es crucial para mejorar el pronóstico en Latinoamérica.

One Case of Sudden Isolated Adrenocorticotropic Hormone (ACTH) Deficiency Diagnosed Based on Repeated Hypoglycemic Attacks

2025-06-17

Tomohide Sato | Cureus

51/w mit Hitzewallungen und Schlafstörung

2025-06-17

Sabine Gehrke-Beck | Zeitschrift für Allgemeinmedizin

Publisher Correction: Effect of hydrocortisone on mortality in patients with severe community-acquired pneumonia

2025-06-16

Nicholas Heming , Lindsay R. Berry , Elizabeth Lorenzi +7 more | Intensive Care Medicine

Adrenal Insufficiency in Adults

2025-06-16

Anand Vaidya , James W. Findling , Irina Bancos | JAMA

Importance Adrenal insufficiency is a syndrome of cortisol deficiency and is categorized as primary, secondary, or glucocorticoid induced. Although primary and secondary adrenal insufficiency are rare, affecting less than 279 … Importance Adrenal insufficiency is a syndrome of cortisol deficiency and is categorized as primary, secondary, or glucocorticoid induced. Although primary and secondary adrenal insufficiency are rare, affecting less than 279 per 1 million individuals, glucocorticoid-induced adrenal insufficiency is common. Observations Primary adrenal insufficiency, which involves deficiency of all adrenocortical hormones, is caused by autoimmune destruction, congenital adrenal hyperplasia, pharmacological inhibition (eg, high doses of azole antifungal therapy), infection (eg, tuberculosis, fungal infections), or surgical removal of adrenal cortical tissue. Secondary adrenal insufficiency is caused by disorders affecting the pituitary gland, such as tumors, hemorrhage, inflammatory or infiltrative conditions (eg, hypophysitis, sarcoidosis, hemochromatosis), surgery, radiation therapy, or medications that suppress corticotropin production, such as opioids. Glucocorticoid-induced adrenal insufficiency is caused by administration of supraphysiological doses of glucocorticoids. Patients with adrenal insufficiency typically present with nonspecific symptoms, including fatigue (50%-95%), nausea and vomiting (20%-62%), and anorexia and weight loss (43%-73%). Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued a supraphysiological dose of glucocorticoids. Early-morning (approximately 8 am ) measurements of serum cortisol, corticotropin, and dehydroepiandrosterone sulfate (DHEAS) are used to diagnose adrenal insufficiency. Primary adrenal insufficiency is typically characterized by low morning cortisol levels (&amp;lt;5 µg/dL), high corticotropin levels, and low DHEAS levels. Patients with secondary and glucocorticoid-induced adrenal insufficiency typically have low or intermediate morning cortisol levels (5-10 µg/dL) and low or low-normal corticotropin and DHEAS levels. Patients with intermediate early-morning cortisol levels should undergo repeat early-morning cortisol testing or corticotropin stimulation testing (measurement of cortisol before and 60 minutes after administration of cosyntropin, 250 µg). Treatment of adrenal insufficiency involves supplemental glucocorticoids (eg, hydrocortisone, 15-25 mg daily, or prednisone, 3-5 mg daily). Mineralocorticoids (eg, fludrocortisone, 0.05-0.3 mg daily) should be added for patients with primary adrenal insufficiency. Adrenal crisis, a syndrome that can cause hypotension and shock, hyponatremia, altered mental status, and death if untreated, can occur in patients with adrenal insufficiency who have inadequate glucocorticoid therapy, acute illness, and physical stress. Therefore, all patients with adrenal insufficiency should be instructed how to increase glucocorticoids during acute illness and prescribed injectable glucocorticoids (eg, hydrocortisone, 100 mg intramuscular injection) to prevent or treat adrenal crisis. Conclusions and Relevance Although primary and secondary adrenal insufficiency are rare, glucocorticoid-induced adrenal insufficiency is a common condition. Diagnosis of adrenal insufficiency involves early-morning measurement of cortisol, corticotropin, and DHEAS. All patients with adrenal insufficiency should be treated with glucocorticoids and instructed how to prevent and treat adrenal crisis.

Đặc điểm rối loạn chuyển hoá ở trẻ mắc hội chứng cushing do sử dụng glucocorticoids

2025-06-16

Nguyễn Ngọc Khánh , Cấn Thị Bích Ngọc | Tạp chí Nghiên cứu Y học

Nghiên cứu mô tả đặc điểm rối loạn chuyển hoá ở 136 trẻ mắc hội chứng Cushing do sử dụng glucocorticoids tại Bệnh viện Nhi Trung ương từ tháng 7 … Nghiên cứu mô tả đặc điểm rối loạn chuyển hoá ở 136 trẻ mắc hội chứng Cushing do sử dụng glucocorticoids tại Bệnh viện Nhi Trung ương từ tháng 7 đến tháng 9/2024. Độ tuổi trung vị của bệnh nhi là 7,15 tuổi. Phân tích tình trạng dinh dưỡng ghi nhận 24,2% trẻ có thừa cân hoặc béo phì, 63,2% cân nặng bình thường và 12,5% suy dinh dưỡng. Xét nghiệm sinh hóa cho thấy 11,5% trẻ có tăng glucose máu, 62,2% tăng cholesterol và 30,3% tăng triglyceride. Gan nhiễm mỡ được phát hiện qua siêu âm ở 10,3% trường hợp. Một số trẻ có biểu hiện rối loạn chuyển hoá ngay cả khi BMI bình thường hoặc thấp. Các bất thường chuyển hoá xuất hiện ở nhiều nhóm tuổi và có thể tiến triển âm thầm nếu không được theo dõi định kỳ. Nghiên cứu nhấn mạnh vai trò của việc phát hiện sớm và theo dõi chuyển hoá thường quy ở trẻ dùng glucocorticoids kéo dài nhằm hạn chế nguy cơ tiến triển thành hội chứng chuyển hoá hoặc bệnh lý tim mạch trong tương lai.

Adrenal Cortex

2025-06-14

| TNM Online

Abstract This International Classification of Diseases for Oncology (ICD‐O‐4C74.0) applies only to carcinomas of the adrenal cortex. It does not apply to tumours of the adrenal medulla or sarcomas. The … Abstract This International Classification of Diseases for Oncology (ICD‐O‐4C74.0) applies only to carcinomas of the adrenal cortex. It does not apply to tumours of the adrenal medulla or sarcomas. The regional lymph nodes are the hilar, abdominal para‐aortic and paracaval nodes. Laterality does not affect the N categories. TNM Clinical Classification includes T –Primary Tumour; N –Regional Lymph Nodes, and M –Distant Metastasis. T –Primary Tumour includes cTX Primary tumour cannot be assessed; cT0 No evidence of primary tumour; cT1 Tumour 5 cm or less in greatest dimension, no extra‐adrenal invasion; cT2 Tumour greater than 5 cm, no extra‐adrenal invasion; cT3 Tumour of any size with local invasion, but not invading adjacent organs; and cT4 Tumour of any size with invasion of adjacent organs. This chapter presents the prognostic factors for survival in adrenal cortical carcinoma.

Diagnostic Strategies for Central Adrenal Insufficiency in Clinical Practice: Authors’ response

2025-06-14

Linus Haberbosch , Christian J Strasburger , Lukas Maurer +1 more | European Journal of Endocrinology

Letter to the Editor: Diagnostic Strategies for Central Adrenal Insufficiency in Clinical Practice

2025-06-14

Ivana Kraljević , Mirsala Solak , A Balasko +2 more | European Journal of Endocrinology

Editorial: Adrenal insufficiency: diagnostic approaches, treatments, and outcomes, volume II

2025-06-13

Agnieszka Pazderska , Carl D. Malchoff , Elena Valassi | Frontiers in Endocrinology

Corrigendum: Delayed diagnosis of the full triad autoimmune polyendocrine syndrome type 2 with adrenal crisis: a case report and literature review

2025-06-03

Zhiwen Yao , Hui Chen , Xiao-Kai Hu +3 more | Frontiers in Immunology

[This corrects the article DOI: 10.3389/fimmu.2025.1563629.]. [This corrects the article DOI: 10.3389/fimmu.2025.1563629.].

Response to letter to the editor, “Observational studies on glucocorticoid harm should always consider confounding by indication.”

2025-06-01

Patricia Katz , Kaleb Michaud | ACR Open Rheumatology

Autoimmune Polyglandular Syndrome Type 2 Presentation with Alopecia Universalis, Hashimoto’s Disease, and Addison’s Disease

2025-06-01

Karla Denisse Sales-Morales , Nazhira Torres-Neme , Vladimir Barrera-Villanueva +1 more | International Medical Case Reports Journal

Autoimmune polyglandular syndrome type 2 (APS2) is characterized by the coexistence of primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes. APS2 frequently includes conditions affecting non-endocrine organs, … Autoimmune polyglandular syndrome type 2 (APS2) is characterized by the coexistence of primary adrenal insufficiency with autoimmune thyroid disease and/or type 1 diabetes. APS2 frequently includes conditions affecting non-endocrine organs, such as alopecia, vitiligo, celiac disease, and autoimmune gastritis associated with vitamin B12 deficiency. We report the case of a 30-year-old male with a history of Hashimoto's disease and alopecia universalis, who presented with diarrhea, anorexia, hypoglycemia, and abdominal pain. Physical examination revealed orthostatic hypotension, a non-tender abdomen, and generalized hair loss. Initial laboratory workup showed hyponatremia and hyperkalemia. Further testing, including serum cortisol, ACTH, aldosterone, and 21-hydroxylase antibodies, confirmed the diagnosis of Addison's disease. The patient was treated with prednisone and fludrocortisone. Only two previous cases of APS2 associated with alopecia universalis have been reported: one with concurrent Crohn's disease and another with hypoparathyroidism. This case highlights the importance of recognizing non-endocrine manifestations in patients with autoimmune endocrinopathies to facilitate earlier diagnosis and management.

ABS0586 UKRAINIAN GUIDELINE FOR THE MANAGEMENT OF GLUCOCORTICOID-INDUCED OSTEOPOROSIS

2025-06-01

N.V. Grygorievа , Volodymyr Kovalenko , Mykola Korzh +7 more | Annals of the Rheumatic Diseases

POS0596 ANALYTICAL TOOLS FOR THERAPEUTIC MONITORING OF ADALIMUMAB

2025-06-01

A. Carlomango , G. González , G Lassabe +1 more | Annals of the Rheumatic Diseases

Observational studies on glucocorticoid harm should always consider confounding by indication: comment on the article Katz et al

2025-06-01

Maarten Boers | ACR Open Rheumatology

ABS0665 CORRELATION BETWEEN Ro52 ANTIBODY POSITIVITY AND ELECTROCARDIOGRAPHIC ALTERATIONS IN PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY

2025-06-01

P. Bizioli , Richard Rovelli , Miguel Ángel Mazzini +5 more | Annals of the Rheumatic Diseases

ABS1027 PROSPECTIVE COHORT STUDY ON COURSE AND PREDICTION OF PAIN AFTER INTRAMUSCULAR GLUCOCORTICOIDS IN PATIENTS WITH INFLAMMATORY ARTHRITIS OR OSTEOARTHRITIS

2025-06-01

D. Ten Cate , S.M. Gerritsen , Maike H M Wientjes +3 more | Annals of the Rheumatic Diseases

POS0767 ACHIEVING REMISSION AND LOW DISEASE ACTIVITY WITH BELIMUMAB VERSUS PLACEBO IN PATIENTS WITH SLE EXCLUDING THE GLUCOCORTICOID COMPONENT FROM TARGET DEFINITIONS: A POST HOC ANALYSIS OF FIVE PHASE 3 TRIALS

2025-06-01

Ioannis Parodis , Julius Lindblom , Rebecca A. Levy +7 more | Annals of the Rheumatic Diseases

POS0014 Repository corticotropin injection (RCI) attenuates inflammatory response in a pre-clinical murine collagen induced arthritis model

2025-06-01

Maripat Corr , Allen R. Place , G. Hsueh +1 more | Annals of the Rheumatic Diseases

ABS0381 RISK FACTORS ASSOCIATED WITH THE INCIDENCE OF FRACTURES IN GLUCOCORTICOID TREATED PATIENTS

2025-06-01

Helena Flórez , K. Cajiao , Josep L. Carrasco +7 more | Annals of the Rheumatic Diseases

POS1100 A SYSTEMATIC REVIEW INVESTIGATING THE RATE OF ADRENAL INSUFFICIENCY AFTER PROTOCOLISED STEROID REGIMENS

2025-06-01

J.A. Bowley , Fiona Pearce , S. Shallish +3 more | Annals of the Rheumatic Diseases

ABS0263 KNOWLEDGE OF CORTICOSTEROID SIDE EFFECTS AMONG PARAMEDICAL STAFF

2025-06-01

Cyrine Abid , Z. Gassara , A. Feki +4 more | Annals of the Rheumatic Diseases

Refractory postoperative hypotension as a manifestation of glucocorticoid-induced adrenal insufficiency

2025-06-01

Deborah Williams , Alan Ma | BMJ Case Reports

Corticosteroids are well-known for causing adrenal insufficiency when taken daily over prolonged periods and carry the risk of life-threatening adrenal crises when stopped or not adequately increased with stress. This … Corticosteroids are well-known for causing adrenal insufficiency when taken daily over prolonged periods and carry the risk of life-threatening adrenal crises when stopped or not adequately increased with stress. This case demonstrates that weekly steroid pulses as part of chemotherapy regimens also carry a risk of adrenal suppression and may become apparent following times of significant physiological stress, such as perioperatively. Furthermore, adrenal function may recover with time following discontinuation of corticosteroids; however, the length of time and extent of recovery vary between patients.

Kortikosteroid-Therapie über alle Altersstufen

2025-06-01

Henrike Ottenjann | InFo Neurologie + Psychiatrie

Sex and age differences in cortisol levels during glucagon stimulation test in children

2025-05-31

Camilla Borghammar , Johan Svensson , Anders Tidblad +1 more | BMC Pediatrics

Abstract Background Previous studies of glucagon stimulation test (GST) in children have shown variable results regarding the utility and reliability of the cortisol response to this test and its correlation … Abstract Background Previous studies of glucagon stimulation test (GST) in children have shown variable results regarding the utility and reliability of the cortisol response to this test and its correlation with clinical parameters. The aim of this study was to assess cortisol levels at GST and to evaluate how clinical parameters, such as age, sex, pubertal status and Body Mass Index (BMI), correlate to cortisol levels in children. Methods A retrospective study of children evaluated for short stature with the GST. Cortisol, glucose and growth hormone (GH) levels at GST, as well as clinical parameters (age, sex, pubertal status, BMI), were collected from medical records. A peak cortisol of ≥ 450 nmol/L was used as a cut-off indicative of a sufficient response. Non-parametric tests were applied in the statistical analysis, and linear regression was used to examine factors affecting cortisol max at the GST. Results In total, 171 children were included; median age 7.8 years (1.0–18.0), 60 (35.1%) female, 23 (13.5%) pubertal. Of all children, 145 (84.8%) achieved a peak cortisol ≥ 450 nmol/L. There was a negative correlation between peak cortisol levels and age (Spearman’s rho − 0.26, p = < 0.001). Peak cortisol levels were higher in females vs. males: 667.5 nmol/L (range 400–995) vs. 602 nmol/L (range 202–1008), p = 0.005. A higher number of boys than girls did not reach the cortisol cut-off value of 450 nmol/L ( p = 0.022). The difference in maximum stimulated cortisol levels between the sexes remained after adjusting for age with a linear regression model (β (95% CI) 65.3 (15.9–114.6), p = 0.01). Conclusion GST is a reliable test of the hypothalamic-pituitary-adrenal (HPA) axis in children. Girls and younger children had higher peak cortisol at GST. The results support a need for sex- and age-dependent reference values for cortisol.

Corticosteroids as adjunctive therapy in the treatment of influenza.

2021-12-01

Louise Lansbury , Chamira Rodrigo , Jo Leonardi‐Bee +2 more

Corticosteroids for treating sepsis in children and adults.

2021-01-01

Djillali Annane , Éric Bellissant , Pierre Edouard Bollaert +5 more

Background Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may benefit patients. The original review was published … Background Sepsis occurs when an infection is complicated by organ failure. Sepsis may be complicated by impaired corticosteroid metabolism. Thus, providing corticosteroids may benefit patients. The original review was published in 2004 and was updated in 2010 and 2015 prior to this update. Objectives To examine the effects of corticosteroids on death in children and adults with sepsis. Search methods We searched CENTRAL, MEDLINE, Embase, LILACS, ClinicalTrials.gov, ISRCTN, and the WHO Clinical Trials Search Portal, on 25 July 2019. In addition, we conducted reference checking and citation searching, and contacted study authors, to identify additional studies as needed. Selection criteria We included randomized controlled trials (RCTs) of corticosteroids versus placebo or usual care (antimicrobials, fluid replacement, and vasopressor therapy as needed) in children and adults with sepsis. We also included RCTs of continuous infusion versus intermittent bolus of corticosteroids. Data collection and analysis All review authors screened and selected studies for inclusion. One review author extracted data, which was checked by the others, and by the lead author of the primary study when possible. We obtained unpublished data from the authors of some trials. We assessed the methodological quality of trials and applied GRADE to assess the certainty of evidence. Review authors did not contribute to assessment of eligibility and risk of bias, nor to data extraction, for trials they had participated in. Main results We included 61 trials (12,192 participants), of which six included only children, two included children and adults, and the remaining trials included only adults. Nine studies are ongoing and will be considered in future versions of this review. We judged 19 trials as being at low risk of bias. Corticosteroids versus placebo or usual care Compared to placebo or usual care, corticosteroids probably slightly reduce 28-day mortality (risk ratio (RR) 0.91, 95% confidence interval (CI) 0.84 to 0.99; 11,233 participants; 50 studies; moderate-certainty evidence). Corticosteroids may result in little to no difference in long-term mortality (RR 0.97, 95% CI 0.91 to 1.03; 6236 participants; 7 studies; low-certainty evidence) and probably slightly reduce hospital mortality (RR 0.90, 95% CI 0.82 to 0.99; 8183 participants; 26 trials; moderate-certainty evidence). Corticosteroids reduced length of intensive care unit (ICU) stay for all participants (mean difference (MD) -1.07 days, 95% CI -1.95 to -0.19; 7612 participants; 21 studies; high-certainty evidence) and resulted in a large reduction in length of hospital stay for all participants (MD -1.63 days, 95% CI -2.93 to -0.33; 8795 participants; 22 studies; high-certainty evidence). Corticosteroids increase the risk of muscle weakness (RR 1.21, 95% CI 1.01 to 1.44; 6145 participants; 6 studies; high-certainty evidence). Corticosteroids probably do not increase the risk of superinfection (RR 1.06, 95% CI 0.95 to 1.19; 5356 participants; 25 studies; moderate-certainty evidence). Corticosteroids increase the risk of hypernatraemia (high-certainty evidence) and probably increase the risk of hyperglycaemia (moderate-certainty evidence). Moderate-certainty evidence shows that there is probably little or no difference in gastroduodenal bleeding, stroke, or cardiac events, and low-certainty evidence suggests that corticosteroids may result in little to no difference in neuropsychiatric events. Continuous infusion of corticosteroids versus intermittent bolus We are uncertain about the effects of continuous infusion of corticosteroids compared with intermittent bolus administration. Three studies reported data for this comparison, and the certainty of evidence for all outcomes was very low. Authors' conclusions Moderate-certainty evidence indicates that corticosteroids probably reduce 28-day and hospital mortality among patients with sepsis. Corticosteroids result in large reductions in ICU and hospital length of stay (high-certainty evidence). There may be little or no difference in the risk of major complications; however, corticosteroids increase the risk of muscle weakness and hypernatraemia, and probably increase the risk of hyperglycaemia. The effects of continuous versus intermittent bolus administration of corticosteroids are uncertain.