Adrenal Insufficiency Research Articles

Perioperative management of patients receiving glucocorticoids in rheumatology

Glucocorticoids are a cornerstone in the management of rheumatic diseases due to their potent anti-inflammatory and immunomodulatory effects. However, their perioperative use presents distinct challenges, including an elevated risk of infection, impaired wound healing, and the potential for glucocorticoid-induced adrenal insufficiency (GI-AI). This review examines the perioperative implications of glucocorticoid therapy, with a focus on infection risk, adrenal insufficiency, and recommendations from clinical practice guidelines. Evidence indicates a correlation between glucocorticoid use and increased perioperative complications, although the efficacy of dose reduction strategies in mitigating these risks remains uncertain. GI-AI, a common complication of prolonged glucocorticoid use, necessitates careful perioperative management to prevent adrenal crises. Guidelines from British, American, and German societies propose slightly differing approaches, albeit with low levels of evidence, emphasizing the importance of individualized patient care.

Impact of Dose Reduction of Topical Steroids to Manage Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis

Impact of Dose Reduction of Topical Steroids to Manage Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis

Orthostatic hypotension in a patient with HIV: uncovering adrenal insufficiency from fluticasone-cobicistat interactions.

Orthostatic hypotension in a patient with HIV: uncovering adrenal insufficiency from fluticasone-cobicistat interactions.

Disordered electron transfer: New forms of defective steroidogenesis and mitochondriopathy.

Most disorders of steroidogenesis, such as forms of congenital adrenal hyperplasia (CAH) are caused by mutations in genes encoding the steroidogenic enzymes and are often recognized clinically by cortisol deficiency, hyper- or hypo-androgenism, and/or altered mineralocorticoid function. Most steroidogenic enzymes are forms of cytochrome P450. Most P450s, including several steroidogenic enzymes, are microsomal, requiring electron donation by P450 oxidoreductase (POR); but several steroidogenic enzymes are mitochondrial P450s, requiring electron donation via ferredoxin reductase (FDXR) and ferredoxin (FDX). POR deficiency is a rare but well-described form of CAH characterized by impaired activity of 21-hydroxylase (P450c21, CYP21A2) and 17-hydroxylase/17,20-lyase (P450c17, CYP17A1); more severely affected individuals also have the Antley-Bixler skeletal malformation syndrome and disordered genital development in both sexes, and hence is easily recognized. The 17,20-lyase activity of P450c17 requires both POR and cytochrome b5 (b5), which promote electron transfer. Mutations of POR, b5, or P450c17 can cause selective 17,20-lyase deficiency. In addition to providing electrons to mitochondrial P450s, FDX and FDXR are required for the synthesis of iron-sulfur clusters, which are used by many enzymes. Recent work has identified FDXR mutations in patients with visual impairment, optic atrophy, neuropathic hearing loss and developmental delay, resembling the global neurologic disorders seen with mitochondrial diseases. Many of these patients have had life-threatening events or deadly infections, often without an apparent triggering event. Adrenal insufficiency has been predicted in such individuals but has only been documented recently. Neurologists, neonatologists and geneticists should seek endocrine assistance in evaluating and treating patients with mutations in FDXR.

Ketamine Versus Etomidate for Rapid Sequence Intubation: A Systematic Review and Meta-Analysis of Randomized Trials.

To compare the safety and efficacy of ketamine and etomidate as induction agents to facilitate emergent endotracheal intubation. We searched MEDLINE, Embase, Cochrane Clinical Trials Register, and ClinicalTrials.gov from inception to April 3, 2024. We included randomized controlled trials (RCTs) that compared ketamine to etomidate to facilitate emergent endotracheal intubation in adults. Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model, assessed risk of bias using the modified Cochrane tool and certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We pre-registered the protocol on PROSPERO (CRD42023472450). We included seven RCTs (n = 2384 patients). Based on pooled analysis, compared with etomidate, ketamine probably increases hemodynamic instability in the peri-intubation period (relative risk [RR], 1.29; 95% CI, 1.07-1.57; moderate certainty) but probably decreases the need for initiation of continuous infusion vasopressors (RR, 0.75; 95% CI, 0.57-1.00; moderate certainty) and results in less adrenal suppression (RR, 0.54; 95% CI, 0.45-0.66; moderate certainty). Ketamine probably has no effect on successful intubation on the first attempt (RR, 1.01; 95% CI, 0.97-1.05; moderate certainty) or organ dysfunction measured as the maximum Sequential Organ Failure Assessment (SOFA) score during the first 3 days in ICU (mean difference, 0.55 SOFA points lower; 95% CI, 1.12 lower to 0.03 higher; moderate certainty) and may have no effect on mortality (RR, 1.00; 95% CI, 0.83-1.21; low certainty) when compared with etomidate. Compared with etomidate, ketamine probably results in more hemodynamic instability during the peri-intubation period and appears to have no effect on successful intubation on the first attempt or mortality. However, ketamine results in decreased need for the initiation of vasopressor use and decreases adrenal suppression compared with etomidate.

A Case of Hypercalcemia and Acute Kidney Injury Caused by Adrenal Insufficiency

A Case of Hypercalcemia and Acute Kidney Injury Caused by Adrenal Insufficiency

Empty sella and reversible central adrenal insufficiency in treated primary hypothyroidism

Introduction: Primary hypothyroidism can be complicated by pituitary-related sequelae. Along with a few other reports, we documented pituitary dysfunction with empty sella in primary hypothyroidism; however, the spontaneous reversibility of the hypopituitarism is rarely reported. We aimed to describe a rare complication of primary hypothyroidism and to emphasize the importance of monitoring such complications. Case Report: We report a previously healthy 59-year-old man who presented four years earlier with weight gain of several months duration. The investigations revealed primary hypothyroidism with thyroxine 5.2 pmol/L (7.8–16) and thyroid stimulating hormone >100 uIU/L (0.27–4.2). He responded well to the thyroxine replacement as he became asymptomatic with normalization of thyroid stimulating hormone (TSH). After a few years, the patient presented with lethargy and postural hypotension despite euthyroidism. The basal and stimulated cortisol levels were low 73 (185–624) and 185 nmol/L respectively, while the adrenocorticotrophic hormone was inappropriately normal at 16.1 pg/mL (10.00–46.00). All the other pituitary hormones were normal. Magnetic resonance imaging showed partial empty sella. The patient preferred conservative management. Subsequently, he showed progressive clinical and hormonal improvement. As scarcely reported in the literature, primary hypothyroidism can be complicated by the development of empty sella, which can further develop pituitary endocrinopathies. Central adrenal insufficiency has been reported more often than other empty sella-related pituitary endocrinopathies, which might need long-term therapy. Conclusion: We documented that empty sella and the associated hypopituitarism might complicate the primary hypothyroidism. This report encourages monitoring, and managing these complications in longer-term follow-up.

Adrenal Disorders in Pregnancy. A Comprehensive Review and Prospects for Future Research

Introduction and purpose: Adrenal disorders cover a spectrum of conditions, including adrenal insufficiency, Cushing's syndrome and others. Each disorder has its own implications for pregnancy and requires an individualised approach. This review aims to provide a comprehensive overview of adrenal disorders during pregnancy, such as endogenous Cushing's syndrome, adrenal insufficiency, primary aldosteronism, and pheochromocytoma. Brief description of the state of knowledge: During pregnancy, a number of adaptive processes take place in a woman's body including changes in the endocrine system. Given all these changes, adrenal diseases pose both diagnostic and therapeutic challenges. The symptoms of adrenal diseases often overlap with those observed during physiological pregnancy. Adrenal disorders during pregnancy if unrecognised or treated inadequately, can lead to negative consequences for the mother and foetus, indicating the importance of awareness of these conditions among physicians. Conclusions: Treating and diagnosing adrenal diseases during pregnancy is a major challenge for doctors. It is crucial to diagnose adrenal diseases in pregnant women as early as possible, and to meticulously plan pregnancies for women diagnosed before conception to prevent the negative consequences of untreated adrenal disorders. Optimal control of treatment before conception should be sought. Access to specialised centres with multidisciplinary teams experienced in treating these conditions is crucial for optimal maternal and foetal care.

Adrenal Crisis and Adrenal Insufficiency Admissions in Patients 30-59 Years: Contribution of Psychosocial Factors.

Adrenal crises (AC) occur in middle aged adults with adrenal insufficiency (AI). Psychosocial difficulties may impede effective self-management in some cases. This study aimed to investigate associations between psychosocial problems and hospital admissions for AI/AC in middle aged adults. Data on all hospitalisations among patients aged 30-59 years with a diagnosis of AI were extracted from a regional database for the years 2005-2020. Trends in hospitalisations and associations between admissions and comorbid psychosocial problems were assessed. Of the 3948 admissions for AI between 2005 and 2020, 63.4% were in women. Admissions increased by 91.4%, from 61.89 to 118.44/million (p < 0.0001), while AC admission rates increased by 176.5% (from 7.71 to 21.33/million, p=NS). Secondary AI (SAI) admissions rose by 133.0%, from 27.98/million to 65.20/million (p < 0.001). Admissions increased in women in each decade but only in males aged 50-59 years. Comorbid infection was identified in 28.1% of admissions and at least one comorbid contributory psychological problem was found in 25.6%. Males, patients with SAI and those not living in a domestic partnership had a higher combined psychosocial problem burden. Females admitted with at least one sign of an AC had significantly higher psychosocial problem scores than those with less severe presentations. These results suggest that psychosocial factors may play a role in some admissions for AI/AC in adults aged between 30 and 59 years, possibly contributing to the otherwise unexplained rise in hospitalisations for AI.

Pregnancy in Primary Ovarian Insufficiency and Hypoplastic Uterus: Case Series

Primary ovarian insufficiency (POI) in women of reproductive age remains unexplained in nearly 90% of cases. Various infections (e.g., mumps, varicella, malaria, shigella, tuberculosis) can destroy healthy ovarian tissue. Rare mutations in genes for FSH and LH receptors, chromosomal abnormalities (e.g., Turner Syndrome, Mosaic Turners, Fragile X FMR1 premutation), and autoimmune diseases (e.g., Addison disease, Hashimoto thyroiditis, rheumatoid arthritis, systemic lupus erythematosus) are also associated with POI. Genetic mutations and autosomal recessive diseases like galactosemia contribute to POI as well. The overall success rate for pregnancy and live birth after assisted reproductive techniques is only 25%. Women with POI should be informed about their condition and future fertility treatment options. For women desiring fertility, cyclical bleeding is preferred to maximize chances of successful embryo transfer or natural pregnancy. Premenopausal women are often prescribed OCPs with a placebo week per month, leading to 12 weeks of estrogen deficiency annually. Oocyte donation remains the best option for achieving successful pregnancy in women with POI, with a 40% probability after one IVF cycle and 70-80% after four cycles.

Diagnosing adrenal insufficiency—something to spit at!

Diagnosing adrenal insufficiency—something to spit at!

Beware of the rinse: magic mouthwash as a rare cause of iatrogenic Cushing syndrome and secondary adrenal insufficiency.

Beware of the rinse: magic mouthwash as a rare cause of iatrogenic Cushing syndrome and secondary adrenal insufficiency.

Sepsis-associated liver injury: Mechanisms and potential therapeutic targets

In this editorial, we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury (SLI) and its treatment. SLI is a serious complication of sepsis, primarily caused by microcirculatory disturbances, the gut-liver axis, and inflammatory responses. Specific treatment recommendations for SLI are lacking. The gut-liver axis represents a potential therapeutic target, with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function. Although immunomodulatory therapies are being explored, anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits. Statins may reduce liver inflammation and prevent injury in sepsis, but their clinical application is limited. Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients, indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency. Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results, likely due to inadequate assessment of the immune status of the host. Future research should prioritize the development of personalized immunotherapy tailored to patients’ immune profiles, focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

Cushing's syndrome and COVID-19.

This review aims to present current data on the course of COVID-19 in patients with Cushing syndrome (CS) and discuss treatment for CS during to the pandemic. Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Cushing syndrome", "Hypercortisolism" and "Glucocorticoid". Chronic hypercortisolism has been reported to increase infectious risk and worsens prognostic of patients with COVID-19 potentially due to its direct impact on the immune system: lymphopenia, impairment of monocytes and neutrophils activity, diminution of complement activation. Main metabolic complications of CS - i.e. diabetes, hypertension and obesity - have been recognized as COVID-19 complications risk factors. Patients with CS treated with steroidogenesis inhibitors might experience adrenal insufficiency during COVID-19. Special attention should be paid to patients with CS and COVID-19. The pandemic has impacted - and delayed - care of chronic illnesses including CS. Specific recommendations had been provided during the pandemic: favor telemedicine consultations, limit in-hospital explorations and postpone surgery when feasible. There are enough evidence for an increased prevalence and severity of COVID-19 to recommend a specific attention and caution in patients with CS.

Severe Hyperkalemia in a Child with Vomiting and Diarrhea

Case Presentation: A 13-month-old child with past medical history of congenital adrenal insufficiency presented to the emergency department with vomiting and diarrhea. Initially the child was noticed to have bradycardia with normal blood pressure. An electrocardiogram (ECG) showed tall T waves, broad QRS complex, and widened PR interval suggestive of severe hyperkalemia. The initial blood gas showed potassium of 10.7 millimoles per liter. The patient was started on calcium gluconate with immediate resolution of ECG changes. Further management with insulin, dextrose, and sodium olystyrene sulfonate led to normal potassium levels. Discussion: Hyperkalemia is a life-threatening condition in children, especially in those with congenital adrenal insufficiency. The ECG showed different changes as the levels of serum potassium levels increased ranging from tall T waves, wide QRS complex, increased PR interval to arrythmias. Immediate treatment with calcium gluconate in such cases has significant cardioprotective effect. It is important to recognize the ECG changes manifested by changes in serum potassium levels. Our patient had classic ECG changes manifested in severe hyperkalemia.

Current status and prospects of congenital adrenal hyperplasia: A bibliometric and visualization study.

Congenital adrenal hyperplasia (CAH) is increasingly prevalent, leading to a surge in related research. To pinpoint emerging trends and recommend future directions, a bibliometric analysis of relevant CAH literature was performed. From January 1, 2000, to October 1, 2023, we searched the Web of Science Core Collection for CAH literature. For the bibliometric analysis, tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed. The United States and England are at the forefront among 113 countries, contributing 5034 papers to CAH research. However, there is a need for more extensive global collaboration across institutions in this field. The number of publications on CAH is increasing annually. Leading research institutions include the University of Michigan, University of California, San Francisco, Karolinska Institutet, and Karolinska University Hospital. The Journal of Clinical Endocrinology & Metabolism is the most cited in this area. The most prolific author is Falhammar H, with 88 publications, 2568 co-citations, and a significant overall contribution. Key research areas include diagnostic methods and therapeutic strategies for CAH. Emerging research hotspots are identified by keywords such as "disorders of sex development," "21-hydroxylase deficiency," "ambiguous genitalia," "testosterone" and "adrenal insufficiency." Research on CAH is expected to expand globally. Future studies will primarily focus on exploring CAH's diagnostic aspects and developing new therapies. This paper will help scholars better understand the dynamic evolution of the CAH and point out the direction for future research.

Recent developments in the diagnosis and treatment of Addison's disease

Recent developments in the diagnosis and treatment of Addison's disease

Adrenal crisis-induced cardiogenic shock (ACCS): a comprehensive review.

Adrenal insufficiency (AI) is a disorder in which inadequate glucocorticoid and mineralocorticoid hormone production leads to a variety of symptoms, including fatigue, weight loss, and nausea. In some patients with unknown AI, adrenal crisis-induced cardiogenic shock (ACCS) can be the first presentation, resulting in a fatal situation. The ACCS may exhibit unresponsiveness to inotropes and fluid therapy; thus, glucocorticoid administration is the primary vital intervention, making early detection of AI essential. Hence, in this study, we review the case reports demonstrating acute cardiomyopathies in the context of AI. The review addresses the suggested underlying mechanisms, including the diminished protective effects of glucocorticoids against catecholamines in AI. We also highlighted some clues to aid physicians in considering AI as a differential diagnosis in critically ill patients presenting cardiogenic shock.

A glucocorticoid-mediated immunoregulatory circuit integrated at brain levels: our early studies and a present view.

Background It was known since the 1940's that pharmacological administration of glucocorticoids can inhibit inflammatory and immune processes, and these hormones are still today among the most widely used therapeutic tools to treat diseases with immune components. However, it became clear later that endogenous glucocorticoids can either support or restrain immune processes. Summary Early studies showed that: a) endogenous levels of glucocorticoids can modulate immune cell activity; b) the immune response itself can stimulate the hypothalamus-pituitary-adrenal (HPA) axis to release glucocorticoids to levels that can exert immunoregulatory effects; c) immune products, later identified as cytokines, mediate this effect. On these bases, the existence of a glucocorticoid-mediated immunoregulatory circuit was proposed. It was also shown that increased levels of endogenous glucocorticoids exert protective effects during infections and other diseases with immune components. However, it was found in animal models and in humans that these effects can be blunted in several immune-linked diseases by defects at several levels, for example by glucocorticoid resistance or by adrenal insufficiency. Evidence was later provided that the glucocorticoid-mediated immunoregulatory circuit can also be activated by cytokines produced not only as consequence of immune stimulation but also following psycho/sensorial and physical stimuli. Thus, this circuit can be integrated at brain levels and, besides stimulating the HPA axis, cytokines can also affect synaptic plasticity, most likely via a tripartite synapse, with astrocytes as neuro-immune cells acting as the third component. Key Messages It is now well established that the glucocorticoid-mediated immunoregulatory circuit plays a central role in maintaining health. However, several variables can condition the efficacy of the effect of endogenous glucocorticoids. Furthermore, since cytokines and other immune products have many other neuro-endocrine and metabolic effects, other neuro-endocrine-immune circuits could simultaneously operate or become predominant during different pathologies. The consideration of these aspects might help to implement strategies to eventually decrease therapeutic doses of exogenous glucocorticoids.

Diagnosis and approach to glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome

Introduction and purpose: Primary adrenal insufficiency can result from diseases affecting the adrenal glands, while secondary adrenal insufficiency is caused by suppression of the hypothalamic-pituitary-adrenal axis. The most common cause of adrenal suppression is exogenous steroids, a condition recently termed glucocorticoid-induced adrenal insufficiency (GIAI). Glucocorticoid-induced adrenal suppression is a common adverse effect of glucocorticoid therapy, which can have severe consequences. This review provides a comprehensive overview of the diagnosis and management of glucocorticoid-induced adrenal insufficiency and glucocorticoid withdrawal syndrome. Material and methods: An extensive examination of articles published in scientific journals was carried out through online research platforms PubMed and Google Scholar. We searched articles by entering keywords in appropriate configuration: “glucocorticoid-induced adrenal insufficiency”, “glucocorticoids”, “steroids”, “adrenal crisis”, “substitution therapy”, “glucocorticoid withdrawal”. Description of the state of knowledge: Glucocorticoids are widely used in the treatment of various inflammatory and autoimmune disorders due to their potent anti-inflammatory and immunosuppressive effects. However, chronic glucocorticoid therapy can lead to a number of adverse effects, including adrenal suppression, which can result in adrenal insufficiency. Summary: Primary care clinicians should recognize the high prevalence of glucocorticoid-induced adrenal insufficiency in patients receiving non-oral glucocorticoid formulations. The glucocorticoid withdrawal syndrome exhibits symptoms analogous to glucocorticoid-induced adrenal insufficiency. Additional data on the morbidity and mortality linked to glucocorticoid-induced adrenal insufficiency is needed to comprehend the associated health risks, which will ultimately guide the approach to care for patients tapering long-term glucocorticoid therapy.