Cushing syndrome (CS) from metastatic adrenocortical carcinoma (ACC) or neuroendocrine tumors (NETs) presents a therapeutic challenge when surgery is not feasible. Liver-directed embolization, including bland transarterial embolization (TAE) and yttrium-90 (Y-90) radioembolization, may palliate hypercortisolism arising from hormonally active hepatic metastases. We conducted a retrospective single-center case series of 4 adult patients (≥18 years) with CS and liver-dominant metastatic ACC or NET who underwent hepatic embolization between 2015 and 2025. Inclusion criteria were: (1) confirmed CS based on standard biochemical testing, and (2) receipt of liver-directed embolization (TAE or Y-90) for hypercortisolism. Exclusion criteria were absence of pre- and postembolization hormonal data preventing biochemical assessment. The primary outcome was biochemical response within 14 days (≥50% reduction or normalization of morning cortisol). Secondary outcomes included duration of biochemical control, radiographic response (RECIST 1.1), and adverse events (CTCAE v5.0). Four patients (2 ACC, 2 NET) underwent Y-90 (n = 1) or TAE (n = 3). All achieved significant cortisol; 2/4 normalized cortisol with transient adrenal insufficiency. The Y-90 patient had sustained remission, while 2 TAE patients achieved partial hormonal control enabling tapering of medical therapy. Radiographically, tumor burden stabilized or improved in most treated lesions. Embolization was well tolerated, with only 1 case of post-embolization syndrome and no procedure-related mortality. One patient died from disease progression; 3 remain alive with controlled or improving disease. Hepatic embolization is a viable palliative option for CS due to unresectable liver-dominant metastases, providing meaningful biochemical improvement with acceptable safety and supporting integration into multidisciplinary CS management.

Clinical Profile of Adrenal Insufficiency: A Study in a Tertiary Care Centre

Addison's disease (AD) results in glucocorticoid and mineralocorticoid deficiencies and is often immune-mediated. While AD is uncommon in dogs, Nova Scotia Duck Tolling Retrievers (NSDTRs) exhibit increased incidence, suggesting genetic predisposition. Detailed clinical evaluation of 24 juvenile-onset cases revealed that while all dogs presented with adrenal insufficiency, at least 10 dogs (41.7%) had concurrent autoimmune conditions. This suggests juvenile-onset AD in NSDTRs represents part of a broader multiple autoimmune syndrome (MAS) with variable expressivity. Strikingly, NSDTRs affected by juvenile-onset AD had severely decreased lifespans, with a median survival of 2 years despite appropriate treatment. Genome-wide association identified a significant association on chromosome 27 (chr27:29,724,286, p = 6.96 × 10- 13). Whole-genome, short-read sequencing identified a recessive missense variant in RESF1 (Chr27:29,736,795). The variant exhibited 76% penetrance for early-onset disease, and the decreased penetrance was not attributable to differences in Dog Leukocyte Antigen (DLA) haplotypes. Immunohistochemistry confirmed T cell infiltration in the adrenal cortex of two unrelated affected dogs, with necropsy findings including severe bilateral lymphocytic adrenalitis, multisystemic granulomatous inflammation, and lymphoplasmacytic conjunctivitis supporting autoimmune pathogenesis. This study identifies RESF1 as a novel gene associated with autoimmune disease in NSDTRs, ranging from isolated juvenile-onset AD to multi-organ autoimmune manifestations. The findings represent a rare example of monogenic autoimmune disease and establish RESF1 as a candidate gene for further investigation of immune tolerance mechanisms.

Introduction Hidradenitis Suppurativa (HS) is an inflammatory skin condition that is typically managed with oral prednisone (OP). Intramuscular triamcinolone injection (ITI) therapy can control HS flares, however, the safety profile of multiple ITIs in HS is unknown. We assess the short-term and long-term risk of adverse effects after multiple ITIs in HS patients, and the one-year risk of adverse effects after receiving ITI or OP. Method Using the TriNetX Research Network between January 1, 2018, and December 31, 2019, we identified 892 HS patients who received one ITI and 892 matched HS patients who received three or more ITIs. We identified 650 HS patients who received three or more ITIs and 650 matched HS patients who received three or more regimens of 20mg OP. Results Compared to single ITI, patients with multiple ITIs did not have a significantly increased one-month or one-year risk of abnormal weight gain, skin infections, hyperglycemia, hypertension, depressive episodes, behavioral syndromes, bacterial and viral infections, or peptic ulcers. There was no increased one-year risk of hyperlipidemia, metabolic syndrome, adrenocortical insufficiency, osteoporosis, cataract, or glaucoma. Compared to OP, there was no significant difference in the one-year risk of abnormal weight gain, hyperlipidemia, osteoporosis, cataract, glaucoma, behavioral syndromes, peptic ulcers, hyperglycemia, depressive episodes, skin infections, or bacterial and viral infections. Patients with OP had a significantly higher risk of hypertension. Discussion We demonstrate that multiple ITIs do not significantly increase the short- or long-term risk of adverse corticosteroid effects compared to multiple regimens of OP or singular ITI.

Primary adrenal insufficiency (PAI) in childhood is a rare and potentially life-threatening condition that may arise from defects in adrenal steroidogenesis, adrenal dysgenesis, ACTH resistance, autoimmune mechanisms, or inherited metabolic disorders. Among the latter, peroxisomal dysfunctions represent a rare cause. Although X-linked adrenoleukodystrophy is a well-recognized etiology, adrenal involvement in other peroxisomal diseases, such as ACOX1 deficiency, remains poorly defined. We report a three-year-old girl with global developmental delay, epilepsy, bilateral sensorineural hearing loss, and progressive neurological regression. Biochemical analyses revealed abnormal plasma very-long-chain fatty acids profile, suggesting a peroxisomal disorder. Whole-exome sequencing identified a homozygous pathogenic variant (c.1478+2T>A) in ACOX1, confirming the diagnosis of pseudo-neonatal adrenoleukodystrophy. During hospitalization for a urinary tract infection, endocrine evaluation revealed markedly elevated plasma ACTH (529 pg/mL) and low serum cortisol (8.62 µg/dL), while Na, K, and PRA were within normal limits. Adrenal imaging was consistent with atrophy. Hydrocortisone replacement was initiated with good clinical response. Notably, the patient had no classical signs of adrenal failure such as hyperpigmentation or electrolyte imbalance. This case provides additional evidence that ACOX1-related Pseudo-neonatal adrenoleukodystrophy may be associated with variable adrenal involvement, expanding the phenotypic spectrum of the disorder. The absence of typical clinical manifestations highlights the importance of routine hormonal screening in children with peroxisomal diseases, even in the absence of overt adrenal symptoms. Early recognition of endocrine dysfunction can prevent life-threatening adrenal crises and offers valuable insight into the broader pathophysiology of peroxisomal β-oxidation disorders.

Topical and systemic corticosteroids in the modern Management of Atopic Eczema: A scoping review.

Exogenous glucocorticoid (GC) therapy, whether physiological replacement in adrenal insufficiency or pharmacological treatment of inflammatory diseases, confers significant cardiometabolic risks, including obesity and insulin resistance. Finding safer alternative GCs is thus a pressing goal. Corticosterone, a minor endogenous GC in humans, may have fewer deleterious metabolic effects than cortisol (hydrocortisone), potentially mediated through selective export via the Abcc1 transporter. In adrenalectomised mice we compared oral corticosterone and cortisol administration and investigated whether Abcc1 mediates differential metabolic effects, and whether such responses are sexually dimorphic. After an initial dose-response study male and female Abcc1-knockout (Abcc1-/-) and wild-type (WT) mice were administered corticosterone or cortisol (25 µg/mL) in drinking water for up to 5weeks. Cortisol induced greater insulin resistance and elevated energy expenditure compared to corticosterone, an effect more pronounced in male mice. Corticosterone-treated Abcc1-/- males, surprisingly, exhibited reduced fat mass and improved insulin sensitivity compared to WT controls. This protective effect of Abcc1 deficiency was neither observed in cortisol-treated mice nor in female mice receiving either treatment. These findings confirm that even at relatively low doses cortisol drives more severe metabolic dysregulation than corticosterone, independent of Abcc1. Paradoxically Abcc1 deletion protects against corticosterone-induced adiposity in males. Moreover sex modulates GC responses. These findings challenge the presumed role of Abcc1 in GC export and highlight the importance of sex in GC action. Together these results underscore corticosterone's potential as a safer GC therapy, advance our understanding of sex-specific GC action and raise novel questions about Abcc1's role in GC regulation. KEY POINTS: Current glucocorticoid therapies carry significant cardiometabolic risks, including obesity and insulin resistance, highlighting the need for safer alternatives. Corticosterone may have fewer harmful metabolic effects than cortisol, hypothesised to result from its selective export from cells by the Abcc1 transporter. In a mouse model of exogenous glucocorticoid excess cortisol induced more severe insulin resistance and increased energy expenditure compared to corticosterone, but only in male mice. Unexpectedly Abcc1-knockout males treated with corticosterone showed reduced fat mass and improved insulin sensitivity, an effect not seen with cortisol or in females. These results challenge the assumed role of Abcc1 in glucocorticoid export, highlight sex differences in glucocorticoid action and support corticosterone's potential as a safer therapeutic option.

Glucocorticoids are essential anti-inflammatory and immunosuppressive agents widely used across medical specialties; however, their indiscriminate and prolonged use has been associated with significant systemic complications . This narrative review aimed to synthesize current evidence on the pathophysiological mechanisms underlying corticosteroid-induced adverse effects and to highlight their clinical implications. A comprehensive literature search was conducted in PubMed/MEDLINE, SciELO, and LILACS, prioritizing publications from the last decade, alongside seminal references. The review examined metabolic, cardiovascular, musculoskeletal, immunological, neuropsychiatric, and ophthalmological complications, with particular emphasis on hypothalamic-pituitary-adrenal axis suppression. Chronic exposure to glucocorticoids was associated with insulin resistance, corticosteroid-induced diabetes, dyslipidemia, central adiposity, hypertension, osteoporosis, myopathy, increased susceptibility to infections, impaired wound healing, mood disturbances, psychosis, cataracts, glaucoma, and risk of adrenal insufficiency after abrupt withdrawal. These effects are often dose- and duration-dependent and may develop insidiously, delaying diagnosis and increasing morbidity. In conclusion, although glucocorticoids remain indispensable in clinical practice, their rational prescription—using the lowest effective dose for the shortest duration—combined with proactive monitoring and patient education, is essential to mitigate preventable iatrogenic harm.

Clinical features, investigation, and management of Addison's disease.

Transaldolase (TALDO) deficiency has a well-characterized phenotype. However, there are few large cohort studies, and little is known about the long term, including the need for organ transplantation. Our aim was to share a long multicenter experience in managing these patients. We retrospectively collected data on 16 patients followed for up to 20 years. Liver involvement was present in all patients, with six presenting liver failure at birth. During long-term follow-up, 10 patients developed cirrhosis and four underwent liver transplantation (LTx). Two patients died from severe liver failure in the first months of life; persistent weight below 4 kg precluded LTx. A third patient died from posttransplant complications at 6 months of life. Five patients developed chronic kidney failure, and in two of them kidney transplantation was considered after the age of 20 years. Patent foramen ovale (PFO) was the most frequent cardiac finding; cardiomyopathy or ventricular dysfunction was diagnosed in five patients. Twelve patients developed chronic cytopenia, all presenting with thrombocytopenia. Hypergonadotropic hypogonadism was found in seven patients; two others developed secondary adrenal cortisol insufficiency and primary hypothyroidism requiring replacement therapy. Mild neurocognitive delay was observed only in a few cases. We described different patterns of liver disease progression. Transplantation should be early considered if indicated for liver insufficiency; in the most severe patients with neonatal onset, achieving sufficient weight for transplantation may be challenging. Our preliminary data suggest that, in older patients, kidney involvement may also warrant consideration of kidney transplantation, which was not previously described for this disease.

Adrenal Emergencies.

Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment through targeted disruption of the physiological pathways that maintain tissue tolerance, but which are co-opted by cancers to evade immunosurveillance. Thus, the resultant T-cell activity often causes immune-related adverse events including immune checkpoint inhibitor-induced inflammatory arthritis (ICI-IA). ICI-IA results in functional impairment that frequently persists, even after ICI discontinuation, with substantial quality-of-life impacts for cancer survivors.A high-quality body of evidence to guide ICI-IA management remains an unmet need. Pharmacological treatment may be prolonged, typically begins with non-specific immunosuppression, including systemic steroids, and is usually only rationalised to more targeted therapy in resistant cases. Moreover, retrospective data suggest the high dose glucocorticoids sometimes used in new-onset ICI-IA may be associated with worse cancer outcomes.Tumour necrosis factor (TNF) inhibition strategies are well established with excellent efficacy and safety profiles in 'spontaneous' inflammatory arthritides including rheumatoid and psoriatic arthritis. Mechanistic evidence from ex vivo and murine studies also supports the utility of anti-TNF therapy for steroid-refractory cases of ICI-IA. Although good clinical responses have been reported in this setting, the REACT trial (REmission induction of Arthritis caused by Cancer ImmunoTherapy) aims to provide randomised and robust clinical evidence for deploying targeted therapy earlier in ICI-IA management. It will test whether up-front anti-TNF therapy can more effectively and quickly control symptoms, reduce glucocorticoid exposure, prevent early ICI discontinuation and increase the frequency of drug-free ICI-IA remission. REACT is a prospective, multicentre, open-label, superiority, two-arm, randomised controlled clinical trial to guide initial therapy for patients with ICI-IA. The trial will compare the current standard of care (initial prednisolone; Arm A) with the anti-TNF drug, adalimumab without glucocorticoids (Arm B).The primary outcome is glucocorticoid-free arthritis remission rate at 24 weeks where remission is defined as: (i) No use of systemic or intra-articular glucocorticoids (except when used for adrenal insufficiency) within 4 weeks prior to assessment at 24 weeks; and (ii) absence of synovitis on clinical examination. The protocol was approved by East Midlands-Leicester South Research Ethics Committee on 31-Oct-2024 (Ref: 24/EM/0202). Participants are required to provide written informed consent. The results of this trial will be disseminated through national and international presentations and peer-reviewed publications. ISRCTN18217497.

Steroid replacement after adrenalectomy for mild autonomous cortisol secretion: Clinical predictors and a practical algorithm.

Cystic fibrosis is a multisystem disorder caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and is characterized by progressive pulmonary decline and exocrine pancreatic insufficiency. People with cystic fibrosis are at risk of multiple endocrine complications that can substantially increase morbidity and mortality, including cystic fibrosis-related diabetes (CFRD) and cystic fibrosis-related bone disease (CFBD). Children and adolescents with cystic fibrosis can also experience compromised growth and delayed puberty, although advances in clinical care and treatment have reduced rates of these complications. However, as people with cystic fibrosis live longer and healthier lives, new health challenges associated with these endocrine complications will become increasingly prevalent, including microvascular and macrovascular disease, obesity, metabolic syndrome, osteoporosis, fractures and earlier onset of perimenopause. In this Review, we summarize current knowledge on the epidemiology, pathophysiology, diagnosis and treatment of CFRD, CFBD, growth and puberty, hypogonadism and infertility, iatrogenic adrenal insufficiency and perimenopause in patients with cystic fibrosis. We also consider future research priorities in the field.

Case report: Unusual presentation of persistent vomiting secondary to adrenal insufficiency.

Growth differentiation factor 15 (GDF15) is a stress-response protein that conveys cellular distress signals to the brain and activates neural pathways leading to weight loss. GDF15 levels are increased in glucocorticoid deficiency; however, multiple factors may influence its levels in patients with primary adrenal insufficiency (PAI). The objective of this study was to determine circulating GDF15 levels in patients with PAI compared with a control group and to assess their associations with other clinical parameters. We included 37 patients (22 females) with autoimmune PAI and 47 healthy controls. Serum GDF15 levels, together with anthropometrical, hormonal and biochemical parameters, were assessed. Patients with PAI had significantly higher circulating GDF15 levels than controls did (1276.8 ± 952.1 vs. 682.8 ± 270.2 pg/mL, p < 0.001). In both groups, GDF15 levels were positively correlated with age (p < 0.001). In patients with PAI, GDF15 showed positive correlations with disease duration and duration of autoimmune thyroid disease, gonadotropin levels, waist-to-hip ratio, and body fat percentage, and negative correlations with DHEAS and sex hormone levels. In conclusion, GDF15 levels are increased in patients with PAI compared with healthy controls and correlate with age and the duration of autoimmune disease.

With the expanding use of immune checkpoint inhibitors (ICIs) in gastric cancer, surgical safety is facing new challenges. Perioperative immune-related adverse events (irAEs) can substantially overlap with postoperative complications in both time course and clinical presentation, increasing the risk of diagnostic confusion, missed or delayed recognition, and potentially fatal outcomes. Integrating evidence from prior studies and real-world clinical experience, this article focuses on perioperative irAEs in gastric cancer that are particularly prone to misclassification, such as ICI-related pneumonitis, hypophysitis, adrenal insufficiency, and hypothyroidism. We systematically summarize their epidemiology and common manifestations and, using a symptom-oriented approach, address typical perioperative scenarios including fatigue, hypotension, electrolyte disturbances, altered mental status, postoperative fever, hypoxemia, dyspnea, cough, and perioperative enzyme abnormalities. Practical diagnostic clues and management strategies are proposed to distinguish irAEs from surgical complications such as infection, hemorrhage, pulmonary complications, myocardial infarction, and surgery-related pancreatic injury. We further emphasize the need to establish a standardized, multidisciplinary team-based perioperative pathway in the era of neoadjuvant immunotherapy, incorporating comprehensive preoperative baseline assessment of cardiac, pulmonary, hepatic, and endocrine function; protocolized postoperative monitoring at key time points; and risk-stratified interventions. When irAEs are suspected, early specialist consultation and timely initiation of immunosuppressive therapy, particularly corticosteroids, are critical to reducing both diagnostic delay and unnecessary overtreatment, thereby maximizing the therapeutic benefit of immunotherapy while safeguarding surgical outcomes.

Chronic opioid use suppresses hypothalamic-pituitary signalling, leading to hypogonadism and adrenal insufficiency. Whether these abnormalities persist following long-term opioid cessation remains unclear. In particular, data on the female gonadal axis are limited, while other endocrine outcomes are predominantly reported in male cohorts. This study examined endocrine function in a long-term prospective cohort of people with opioid use disorder, comparing those in sustained remission with those continuing opioid use, exploring associations with opioid exposure, sex and depression. Prospective cohort study using data from the Australian Treatment Outcome Study 18-20 year follow-up. Participants underwent a structured interview and fasting endocrine assessment, including gonadal, adrenal, thyroid, and prolactin measurements. Endocrinopathies were defined using prespecified biochemical and clinical criteria. Prevalence was compared between opioid-free and opioid-using participants. Associations with opioid exposure, sex and depression were examined using Firth logistic regression. Among 123 participants with complete endocrine data, 71 (57.7%) had at least one endocrinopathy. Thirty-five participants (28.4%) were opioid-free. Hypogonadism was markedly less common in opioid-free participants (3.3% vs. 26.7%), and no opioid-free participant had hypocortisolism, compared with 14.8% of those with continuing opioid use. Methadone dose, male sex, and depression were independently associated with hypogonadism. Men prescribed methadone had significantly lower testosterone and luteinising hormone levels. No participant with hypogonadism or hypocortisolism had been previously diagnosed or treated. Opioid-induced endocrine suppression appears reversible with sustained opioid abstinence. Higher methadone dose, male sex, and depression were associated with hypogonadism. Despite frequent healthcare contact, patients remained undiagnosed, highlighting a gap in clinical awareness of opioid-associated endocrinopathies and the need for routine screening in opioid agonist treatment settings.

To examine the variability in neonatologists' screening and management practices of corticosteroid-induced adrenal insufficiency (adrenal suppression; AS) in the NICU. A cross-sectional survey was disseminated nationally via REDCap® to 160 neonatologists who serve as members of Children's Hospitals Neonatal Consortium. Descriptive statistics were used to capture variability in AS screening modalities, diagnostic tools, management approaches, and discharge planning. Of the 82 respondents, only 56.1% screen infants for AS following prolonged systemic corticosteroid exposure, 46.3% after 2-4 weeks, 59.8% utilizing ACTH stimulation testing. Only 2.4% screen after prolonged high dose inhaled corticosteroids, reflecting uncertainty regarding their suppressive potential. Additionally, only 30.5% provide structured caregiver AS education at discharge. Variable nationwide screening and management of adrenal suppression in the NICU underscores uncertainty and inconsistency in practice, revealing the need for clinical guidelines to optimize care.

Familial glucocorticoid deficiency type 2 (FGD2) is a rare autosomal disorder caused by an melanocortin 2 receptor accessory protein ( MRAP ) mutation, typically presenting with hyperpigmentation, recurrent hypoglycemia, and preserved mineralocorticoid function. We describe a 2-year-old male child with tall stature, diffuse hyperpigmentation, recurrent infections, and hypoglycemic seizures. Endocrine evaluation confirmed isolated cortisol deficiency with markedly elevated adrenocorticotropic hormone, and genetic testing identified a pathogenic MRAP variant. Hydrocortisone replacement led to improved pigmentation and stabilization of glucose. This case highlights the importance of considering FGD2 in atypical presentation of primary adrenal insufficiency and emphasizes that early genetic confirmation and timely steroid therapy improve outcomes.