Search Results (51)

Background/Objective: One third of “non-functioning adrenal tumours” (NFAs) have mild autonomous cortisol secretion (MACS). An updated analysis of the hormonal biomarkers profile, including risk factors and the rate of post-surgery adrenal insufficiency (PSAI), the duration of restoring the normal adrenocortical function in MACS/NFA and potential impacts on clinical comorbidities. Methods: Comprehensive review based on PubMed search (January 2020–January 2025). Results: The studies (n = 14) included 2623 patients (N = 1158 underwent unilateral adrenalectomy), aged 18–93 (mean = 57.49 years), with a female-to-male ratio = 1.54. Post-adrenalectomy (n = 9, N = 753) analysis: the PSAI risk correlated with the severity of baseline hypercortisolism. PSAI incidence: 50% of MAC. The rate after 4–6 weeks follow-up was 71.9% (adrenal Cushing’s syndrome) vs. 50% (MACS) vs. 14.4% (NFA). PSAI duration was up to 35 months. Early PSAI diagnosis was reflected by post-operative cortisol assay on day 1 (cut-off ≤ 5 µg/dL) and an ACTH (Cosyntropin) stimulation test (CST) (cortisol cut-off ≤ 14 µg/dL). Pre-operatory PSAI predictors: higher serum cortisol-DST (1 mg dexamethasone testing) and lower baseline plasma ACTH (not all studies agreed). Conclusions: A stratified strategy is encouraged following a unilateral adrenalectomy in MACS; PSAI is expected in almost half of patients, with a potential improvement of hypertension. Serum cortisol assays serve as most useful biomarker as pre-operatory PSAI predictor (after DST) and, potentially, in addition with baseline ACTH. Post-surgery basal cortisol measurement (± CST) helps the decision of glucocorticoids replacement since first post-operative day and during follow-up, serial testing at 3 months is a useful tool. Full article

Glucocorticoids (GCs), such as dexamethasone (DEX), are commonly administered to glioblastoma (GBM) patients to control cerebral edema; however, their effects on immune checkpoint regulation in tumor cells remain insufficiently characterized. This study examined the impact of DEX on the expression of programmed death-ligand 1 (PD-L1) and glucocorticoid-induced leucine zipper (GILZ), a downstream effector of glucocorticoid receptor (GR) signaling, in the U87 and U251 glioblastoma cell lines. DEX consistently induced GILZ expression in both models yet elicited divergent effects on PD-L1: suppression in U87 cells and upregulation in U251 cells. In U87 cells, DEX-induced PD-L1 downregulation was accompanied by accelerated cell cycle progression, suggesting a dual impact on tumor immune evasion and proliferation. Mechanistically, GILZ silencing restored ERK phosphorylation and reversed PD-L1 suppression, whereas GILZ overexpression further decreased PD-L1 levels, implicating a GILZ–ERK pathway in the control of PD-L1. These findings uncover a previously unrecognized GR–GILZ–PD-L1 regulatory axis in glioblastoma cells. While these results are based on in vitro models, they provide a rationale for future in vivo studies to determine whether modulation of GILZ may influence immune checkpoint dynamics and therapeutic responsiveness in GBM. Full article

Background/Objectives: Children with congenital adrenal hyperplasia (CAH) face significant risks of impaired growth and metabolic disturbances despite standard glucocorticoid therapy. This cross-sectional study aimed to evaluate growth outcomes, nutritional status, and associated factors among children with CAH treated in a Vietnamese tertiary pediatric center. Methods: We assessed 201 children aged 1.1–16.5 years in a tertiary pediatric center in Vietnam for anthropometric parameters, biochemical markers (calcium, phosphate, 25-hydroxyvitamin D), and clinical features. Growth status was evaluated using WHO standards, and bone age was assessed radiographically. Statistical analyses explored associations between growth outcomes and clinical, biochemical, and treatment-related factors. Results: Stunting was present in 16.4% of children, while 53.3% were overweight or obese. Bone age advancement occurred in 51.7% of cases. Vitamin D insufficiency or deficiency was detected in 85.6% of patients, and hypocalcemia was present in 85.1%. Overweight/obesity, vitamin D deficiency, and bone age advancement were associated with older age, prolonged corticosteroid therapy, higher androgen levels, and clinical features of treatment imbalance (e.g., Cushingoid appearance, hyperpigmentation). Female sex was significantly associated with higher rates of stunting. Conclusions: Growth impairment, nutritional deficiencies, and skeletal maturation disturbances are prevalent among children with CAH in Vietnam. Early identification of risk factors and the implementation of tailored management strategies that address both endocrine and nutritional health are crucial for optimizing long-term outcomes. Full article

Mpox (MPX), caused by the Monkeypox virus (MPXV), is a zoonotic orthopoxvirus infection with increasing global relevance due to sustained human-to-human transmission. While primarily known for cutaneous and systemic involvement, emerging evidence suggests that MPX may also disrupt endocrine function. This narrative review aims to synthesize current clinical, experimental, and epidemiological findings on MPX-related endocrine complications. We explore the potential impact of MPXV on the thyroid, adrenal glands, and gonads, and discuss the underlying mechanisms, clinical manifestations, and implications for patient management. MPX has been implicated in viral-induced subacute thyroiditis, with cases exhibiting thyrotoxicosis followed by hypothyroidism, likely mediated by direct viral infiltration or immune dysregulation. Additionally, MPX may contribute to adrenal insufficiency through viral invasion, immune-mediated destruction, or hypothalamic–pituitary–adrenal (HPA) axis dysfunction, exacerbating metabolic and inflammatory complications. MPXV’s persistence in testicular tissue raises concerns about reproductive health, with potential implications for fertility, hormone production, and viral transmission. The virus may also modulate host steroid pathways through interactions with glucocorticoid, androgen, and estrogen receptors, influencing immune responses and disease severity. Given these findings, clinicians should maintain vigilance for endocrine dysfunction in MPX patients, particularly in immunocompromised individuals. The role of steroid therapy in MPX remains complex, requiring careful balancing of its anti-inflammatory benefits against potential risks of viral persistence and immune suppression. Further research is essential to clarify MPX’s endocrine impact and optimize management strategies. Full article

Background/Objectives: Spinal cord injury (SCI) causes profound autonomic and endocrine dysfunctions, giving rise to adrenal insufficiency (AI), which is marked by a reduction in steroid hormone production. Left unaddressed, SCI-related AI (SCI-AI) can lead to life-threatening consequences such as severe hypotension and shock (i.e., adrenal crisis). However, symptoms are often non-specific, making AI challenging to distinguish from similar or overlapping cardiovascular conditions (e.g., orthostatic hypotension). Additionally, the etiology of SCI-AI remains unknown. This review aimed to synthesize the current literature reporting the prevalence, symptomology, and management of SCI-AI. Methods: A systematic search was performed to identify studies reporting AI following the cessation of glucocorticoid treatments in individuals with traumatic SCI. A random-effects meta-analysis was conducted to investigate the overall prevalence of SCI-AI. Results: Thirteen studies involving 545 individuals with traumatic SCI, most with cervical level injuries (n = 256), met the review criteria. A total of 4 studies were included in the meta-analysis. Primary analysis results indicated an SCI-AI pooled prevalence of 24.3% (event rate [ER] = 0.243, 95% confidence interval [CI] = 0.073–0.565, n = 4). Additional sensitivity analyses showed a pooled prevalence of 46.3% (ER = 0.463, 95%CI = 0.348–0.582, n = 2) and 10.8% (ER = 0.108, 95%CI = 0.025–0.368, n = 2) for case–control and retrospective cohort studies, respectively. High-dose glucocorticoid administration after SCI as well as the injury itself appear to contribute to the development of AI. Conclusions: The estimated prevalence of AI in people with traumatic SCI was high (24%). Prevalence was also greater among individuals with cervical SCI than those with lower-level lesions. Clinicians should be vigilant in recognizing the symptomatology and onset of SCI-AI. Further research elucidating its underlying pathophysiology is needed to optimize glucocorticoid administration for remediating AI in this vulnerable population. Full article

Background: Takayasu’s arteritis (TA) is a systemic vasculitis that primarily affects the aorta and major arteries. Despite aggressive treatment with glucocorticoids (GCs) and non-biological disease-modifying antirheumatic drugs (nbDMARDs), about 30% of patients experience resistance to therapy or relapse. This study aimed to identify risk factors associated with refractory and relapse TA in pediatric patients. Methods: A retrospective, open-label, case–control study was conducted with 56 pediatric patients with TA diagnosed between February 2011 and October 2022. Fourteen patients were excluded due to insufficient data in their medical records, leaving 42 for further analysis. The patients were divided into two groups: Group 1 (18 patients) with no evidence of relapse and Group 2 (24 patients) with relapse despite first-line treatment at the end of the follow-up period. Clinical, laboratory, and instrumental data were collected and analyzed using R v4.2 and Python v3.10. Results: The median time to relapse was 18 [IQR: 13; -] months according to the Kaplan–Meier curve. Patients with ITAS.A with a diagnosis of TA ≥ 12 had a higher probability of relapse, according to the log-rank criterion (p = 0.006). Symptoms of critical ischemia, such as limb claudication, were more common in Group 2 at diagnosis (p = 0.047), and a trend toward a longer diagnostic delay was observed (p = 0.067). Conclusions: Pediatric patients with an initial ITAS.A score above 12 have a higher risk of relapse when treated with a combination of GCs and nbDMARDs as first-line treatment. Further research is needed to identify high-risk patients more accurately and optimize therapeutic strategies. Full article

Background: The leading cause of blindness due to non-infectious uveitis is cystoid macular edema (CME). Behçet’s disease (BD) is one of the most commonly conditions related to CME. Objectives: To compare the effectiveness and safety of adalimumab (ADA), infliximab (IFX) and certolizumab (CZP) in refractory CME due to BD. Methods: Multicenter study of BD-CME patients with no response to glucocorticoids (GCs) and at least one conventional immunosuppressive drug. At baseline, all patients presented CME, defined by OCT > 300 µ. The effectiveness of ADA, IFX and CZP was assessed over a 2-year period from baseline using the following ocular parameters: macular thickness (µm), visual acuity (BCVA), anterior chamber (AC) cells and vitritis. Mixed-effects regression models were applied. Results: a total of 50 patients (75 eyes) were studied (ADA = 25; IFX = 15 and CZP = 10). No significant differences in demographic parameters were found among the three groups. However, individuals in the CZP group had a significantly extended time from diagnosis to treatment onset (72 (36–120) months, p = 0.03) and had received a higher number of biological therapies (1.7 ± 1.1) compared to the ADA and IFX groups. Within the CZP group, ADA and IFX were previously administrated in seven patients. After 2 years of follow-up, a rapid and sustained reduction in macular thickness was noted in all three groups with no significant differences between them. Additionally, enhancements in BCVA, AC cells and vitritis were also observed. No serious adverse events were reported in the CZP group, although one isolated case of bacteremia was documented in the ADA group. ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Conclusions: ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Full article

Glucocorticoids (GS) are widely used in multiple medical indications due to their anti-inflammatory, immunosuppressive, and antiproliferative effects. Despite their effectiveness in treating respiratory, skin, joint, renal, and neoplastic diseases, they dysregulate glucose metabolism, leading to steroid-induced diabetes (SID) or a significant increase of glycemia in people with previously diagnosed diabetes. The risk of adverse event development depends on the prior therapy, the duration of the treatment, the form of the drug, and individual factors, i.e., BMI, genetics, and age. Unfortunately, SID and steroid-induced hyperglycemia (SIH) are often overlooked, because the fasting blood glucose level, which is the most commonly used diagnostic test, is insufficient for excluding both conditions. The appropriate control of post-steroid hyperglycemia remains a major challenge in everyday clinical practice. Recently, the most frequently used antidiabetic strategies have been insulin therapy with isophane insulin or multiple injections in the basal–bolus regimen. Alternatively, in patients with lower glycemia, sulphonylureas or glinides were used. Taking into account the pathogenesis of post-steroid-induced hyperglycemia, the initiation of therapy with glucagon-like peptide 1 (GLP-1) analogs and dipeptidyl peptidase 4 (DPP-4) inhibitors should be considered. In this article, we present a universal practical diagnostic algorithm of SID/SIH in patients requiring steroids, in both acute and chronic conditions, and we present a new pharmacotherapy algorithm taking into account the use of all currently available antidiabetic drugs. Full article

Background and Objectives: Adrenal insufficiency (AI) can be a significant concern in patients with transfusion-dependent homozygous beta thalassemia (bThal) due to the chronic disease burden and frequent blood transfusions that these patients require. The prevalence of AI in this population remains unclear, with studies often lacking control groups for comparison. This meta-analysis aimed to estimate the proportion of patients with transfusion-dependent bThal who exhibit evidence of AI. Materials and Methods: A systematic review following PRISMA guidelines identified 19 studies for analysis. Results: Despite the variability in the diagnostic methods used to ascertain AI, the meta-analysis revealed that approximately one-third of patients had evidence of AI, with the prevalence rising to 50% in studies focused on adults with bThal. Conclusions: These findings suggest an increased risk of AI in patients with bThal compared to the general population. Clinicians should consider tailored management strategies, including glucocorticoid coverage during surgical procedures, to mitigate the risk of adrenal crises in this vulnerable patient group. Further research is needed to optimize adrenal surveillance and management in patients with bThal. Full article

When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged. For these reasons, corticosteroid-sparing and corticosteroid-replacing therapies are often required for sarcoidosis. Unfortunately, many healthcare providers who care for sarcoidosis patients are not familiar with the use of these agents. In this manuscript, we provide a review of the pharmacotherapy of sarcoidosis. We discuss the mechanism of action, dosing, side-effect profile, approach to monitoring and patient counselling concerning glucocorticoids, and the common alternative drugs recommended for use in the recent European Respiratory Society (Lausanne, Switzerland) Sarcoidosis Treatment Guidelines. We also discuss the use of these agents in special situations including hepatic insufficiency, renal insufficiency, pregnancy, breastfeeding, vaccination, and drug–drug interactions. It is hoped that this manuscript will provide valuable practical guidance to clinicians who care for sarcoidosis patients. Full article

Combination therapy with glucocorticoids, cyclophosphamide, and plasmapheresis is recommended as the standard treatment for anti-glomerular basement membrane (anti-GBM) disease, but the prognosis of this disease remains poor. Several immunobiological agents have been administered or are expected to be useful for anti-GBM disease in light of refractory disease or the standard treatments’ tolerability. Many data regarding the use of biologic agents for anti-GBM disease have accumulated, verifying the effectiveness and potential of biologic agents as a new treatment option for anti-GBM disease. Tumor necrosis factor (TNF) inhibitors were shown to be useful in animal studies, but these agents have no clinical use and were even shown to induce anti-GBM disease in several cases. Although the efficacy of the TNF-receptor antagonist has been observed in animal models, there are no published case reports of its clinical use. There are also no published reports of animal or clinical studies of anti-B-cell-activating factor, which is a member of the TNF family of agents. Anti-interleukin (IL)-6 antibodies have been demonstrated to have no effect on or to exacerbate nephritis in animal models. Anti-C5 inhibitor was observed to be useful in a few anti-GBM disease cases. Among the several immunobiological agents, only rituximab has been demonstrated to be useful in refractory or poor-tolerance patients or small uncontrolled studies. Rituximab is usually used in combination with steroids and plasma exchange and is used primarily as an alternative to cyclophosphamide, but there is insufficient evidence regarding the efficacy of rituximab for anti-GBM disease, and thus, randomized controlled studies are required. Full article

Glucocorticoid excess is a known risk factor for non-alcoholic fatty liver disease (NAFLD). Our objective was to analyse the impact of glucocorticoid replacement therapy on the development of NAFLD and NAFLD-related fibrosis and, therefore, on cardiovascular as well as hepatic morbidity in patients with adrenal insufficiency. Two hundred and fifteen individuals with primary (n = 111) or secondary (n = 104) adrenal insufficiency were investigated for hepatic steatosis and fibrosis using the fatty liver index (FLI), NAFLD fibrosis score (NAFLD-FS), Fibrosis-4 Index (FiB-4) plus sonographic transient elastography. Results were correlated with glucocorticoid doses and cardiometabolic risk parameters. The median dose of hydrocortisone equivalent was 20 mg daily, with a median therapy duration of 15 years. The presence and grade of hepatic steatosis and fibrosis were significantly correlated with cardiometabolic risk factors. We could not find any significant correlations between single, daily or cumulative doses of glucocorticoids and the grade of liver steatosis, nor with fibrosis measured via validated sonographic techniques. In patients with adrenal insufficiency, glucocorticoid replacement within a physiological range of 15–25 mg hydrocortisone equivalent per day does not appear to pose an additional risk for the development of NAFLD, subsequent liver fibrosis, or the cardiovascular morbidity associated with these conditions. Full article

A 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient’s hospitalization, the patient developed liver insufficiency. Urine was submitted for toxicological screening and revealed detection of a trace concentration of alpha-amanitin. The patient was treated supportively for alpha-amanitin intoxication and was discharged from the hospital on day 8, with most biochemical parameters being markedly improved. The patient was persistently hyporexic at the time of discharge. On day 15, at a recheck appointment, the patient had lost 2.4 kg and liver enzymology revealed improved values. On day 24, the patient was presented for anorexia and vomiting and had lost another 2.3 kg. Blood work and endocrinological testing at that time were consistent with hypoadrenocorticism. The patient was started on glucocorticoids and mineralocorticoids. At day 106, the patient was doing well clinically while receiving monthly mineralocorticoids and daily glucocorticoids. This case report is the first to describe the chronological association between alpha-amanitin-induced liver dysfunction and the subsequent development of adrenal insufficiency in a dog. Full article

The diagnosis of adrenal insufficiency (AI) requires a high index of suspicion, detailed clinical assessment including detailed drug history, and appropriate laboratory evaluation. The clinical characteristics of adrenal insufficiency vary according to the cause, and the presentation may be myriad, e.g. insidious onset to a catastrophic adrenal crisis presenting with circulatory shock and coma. Secondary adrenal insufficiency (SAI) often presents with only glucocorticoid deficiency because aldosterone production, which is controlled by the renin angiotensin system, is usually intact, and rarely presents with an adrenal crisis. Measurements of the basal serum cortisol at 8 am (<140 nmol/L or 5 mcg/dL) coupled with adrenocorticotrophin (ACTH) remain the initial tests of choice. The cosyntropin stimulation (short synacthen) test is used for the confirmation of the diagnosis. Newer highly specific cortisol assays have reduced the cut-off points for cortisol in the diagnosis of AI. The salivary cortisol test is increasingly being used in conditions associated with abnormal cortisol binding globulin (CBG) levels such as pregnancy. Children and infants require lower doses of cosyntropin for testing. 21-hydoxylase antibodies are routinely evaluated to rule out autoimmunity, the absence of which would require secondary causes of adrenal insufficiency to be ruled out. Testing the hypothalamic–pituitary–adrenal (HPA) axis, imaging, and ruling out systemic causes are necessary for the diagnosis of AI. Cancer treatment with immune checkpoint inhibitors (ICI) is an emerging cause of both primary AI and SAI and requires close follow up. Several antibodies are being implicated, but more clarity is required. We update the diagnostic evaluation of AI in this evidence-based review. Full article

By definition, children constitute a vulnerable population, especially when they are chronically ill and/or disabled. A characteristic of chronically ill and disabled children is that they also suffer from indirect effects of their disease, such as immobilization, chronic inflammation, reduced time outdoors in the sun, osteotoxic effects of disease-targeted therapy (like glucocorticoids), and poor nutrition. All these factors may lead to bone fragility due to secondary osteoporosis, a co-morbidity that may be overlooked in the context of serious underlying diseases. The ultimate goal of osteoporosis diagnosis and monitoring in this setting is the early identification, prevention, and treatment of low-trauma long bone and vertebral fractures; indeed, vertebral fractures are a frequently under-diagnosed manifestation of overt bone fragility in this context. Efforts to prevent first-ever fractures are also meritorious, including encouragement of weight-bearing activities, optimization of nutritional status, including calcium and vitamin D supplementation, and the diagnosis and treatment of delayed growth and puberty; however, these conservative measures may be insufficient in those at high risk. Numerous natural history studies have shown that vertebral fractures are more common than non-vertebral (i.e., long bone) fractures in at-risk children. Not surprisingly, the cornerstone of secondary osteoporosis monitoring is lateral spine imaging for the early detection of vertebral collapse. Although dual-energy x-ray absorptiometry (DXA) is the gold standard to measure bone mineral density, digital X-ray radiogrammetry may be used as a surrogate measure of bone strength if dual-energy x-ray absorptiometry is not available. In the event that preventive measures fail, treatment with bisphosphonates may be appropriate. Typically, treatment with intravenous bisphosphonates is reserved for children with overt bone fragility and limited potential for spontaneous recovery. However, there is increasing attention to very high-risk children, such as boys with Duchenne muscular dystrophy, who may benefit from bisphosphonate therapy prior to first-ever fractures (given their high fracture frequency and essentially absent potential for spontaneous recovery). This article provides a contemporary overview of the definition and diagnosis of osteoporosis in children with chronic illness, along with the approach to monitoring those at risk and the evidence for currently recommended intervention strategies. Full article