A bioactive protein from Dioscorea polystachya residue alleviates hydrocortisone-induced erectile dysfunction in rats via TXNIP/NLRP3 pathway inhibition.

Objective: Oral ulcers are common lesions that negatively affect patients’ quality of life due to pain, inflammation, and discomfort. The aim of this study was to develop and evaluate mucoadhesive nanofiber formulations containing hydrocortisone (HC) for the local treatment of oral ulcers. Material and Method: Different types of Eudragit (E100, S100, L100-55) and polyvinylpyrrolidone (PVP) were used as mucoadhesive polymers. Nanofibers were fabricated using electrospinning system. Nanofibers characterized by differential scanning calorimetry (DSC), mechanical testing, contact angle measurements, and ex vivo mucoadhesion studies for buccal application. Result and Discussion: Nanofibers were successfully produced with electrospinning. Thermal analyses confirmed the HC within the nanofibers. Mechanical and wettability studies showed that the nanofibers had suitable physical properties for buccal application. In ex vivo mucoadhesion tests of the formulations, values were 0.20 ± 0.05, 0.12 ± 0.03, and 0.14 ± 0.01 mJ cm⁻² for E2-HC, L2-HC, and S2-HC, respectively. Mucoadhesion tests demonstrated strong adhesion to the mucosal surface, indicating potential for extended residence time and effective local drug delivery. In vitro release profiles of formulations, HC released 40.26%, 47.87% and 47.03% at 1 h for E2-HC, L2-HC and S2-HC, respectively. The formulations demonstrated sustained release and favorable mucoadhesive strength, indicating potential clinical applicability. Hydrocortisone-loaded buccal electrospun nanofibers showed promise as a novel and effective drug delivery platform in the treatment of oral ulcers.

Effect of Systemic Hydrocortisone in Ventilated Infants Born Preterm: Mortality and 5.5-Year Neurodevelopmental Outcomes of a Randomized Clinical Trial.

Ratiometric fluorescence sensor based on carbon quantum dots for hydrocortisone detection in food samples.

Study on the absorption mechanism of glucocorticoids in the stratum corneum.

BackgroundInfection is a pathogenetic factor for bronchopulmonary dysplasia (BPD), and corticosteroids are often used for its prevention or treatment. However, few studies have examined their combined effects on brain injury in the context of infection.MethodsRat pups received lipopolysaccharide (LPS) on postnatal Day 1 (P1), followed by tapering doses of dexamethasone (Dex) or hydrocortisone (HC) from P2 to P4. We measured body and brain weights, TUNEL-positive cell counts, synaptic protein levels, and mRNA expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in six brain regions at P5.ResultsThe LPS-HC and LPS-Dex groups showed more TUNEL-positive cells in the hippocampus, cerebellum, and brain stem compared to LPS-naïve controls. Oligodendrocyte precursor cells were the predominant TUNEL-positive cells in the hippocampus and brain stem. Additionally, the LPS-Dex or LPS-HC group showed significantly reduced levels of postsynaptic density protein 95 (PSD95), a postsynaptic protein, in these regions, while treatment with Dex or HC alone did not impact PSD95 expression. GR mRNA was significantly reduced in cortex, striatum, hippocampus, and cerebellum in LPS-HC group, with MR mRNA reduction limited primarily to the striatum.ConclusionsLPS sensitized the immature brain to Dex or HC-related cell death to possible apoptosis and augmented the LPS-induced disruption of synaptic integrity in certain brain regions, potentially via altered GR and MR expression that may modulate corticosteroid receptor signaling.

This study aimed to optimize the culture conditions for equine mammary epithelial cells (EMECs) by investigating the effects of fetal bovine serum (FBS), hydrocortisone (HYD), insulin (INS), and epidermal growth factor (EGF) on cell growth and function. The primary objectives were to identify the optimal culture conditions for EMECs, evaluate the impact of FBS, HYD, INS, and EGF on cell viability and milk component synthesis, and uncover genes involved in mare lactation and milk production. The optimal FBS concentration for cell survival was determined to be 15%, with further improvements achieved through the individual addition of 1 μg/mL HYD, 5 μg/mL INS, and 5 ng/mL EGF. Orthogonal analysis revealed that the combination of 1 μg/mL HYD and 5 ng/mL EGF resulted in the highest survival rates. This combination significantly increased triglyceride and lactose production by 86.36% and 33.33%, respectively (P < 0.01), and β-casein levels by 30.10% (P < 0.05), compared to the control. Transcriptome sequencing identified 596 upregulated and 432 downregulated genes, including laminin subunits (LAMA2, LAMA3, LAMA4, LAMA5), laminin gamma-1 (LAMC1), collagen type IV α1 chain (COL4A1), fatty acid synthase (FASN), and forkhead box protein O1 (FOXO1). Functional enrichment analysis highlighted key pathways related to cell adhesion, bioadhesion, cell-cell signaling, ECM-receptor interactions, and the PI3K-Akt signaling pathway. These findings demonstrate that the addition of HYD, INS, and EGF, both individually and in combination, enhances EMEC viability and milk component synthesis, offering new insights into the molecular mechanisms of mare lactation and milk production.

Background/Objectives: Systemic hydrocortisone (HCS) in very low birth weight (VLBW) infants is commonly used to treat early hypotension or prevent bronchopulmonary dysplasia. This study evaluated the associations between postnatal HCS exposure and neurodevelopment in VLBW infants by comparing regional brain volume at term-equivalent age (TEA) with neurodevelopmental outcomes in early infancy. Methods: This retrospective cohort study included VLBW infants admitted to a neonatal intensive care unit (NICU) between 2013 and 2019. The cumulative HCS dose during hospitalization was recorded, and regional brain volumes were analyzed using magnetic resonance imaging at TEA. Neurodevelopmental outcomes were assessed at a corrected age for prematurity of 18–24 months. Results: Among 146 infants, 57 were classified in the high HCS group (>90 mg/kg) and 89 in the low HCS group (≤90 mg/kg HCS). Bronchopulmonary dysplasia, periventricular leukomalacia, and sepsis were more frequent in the high HCS group. Ninety-five infants underwent magnetic resonance imaging, which revealed reduced brain volumes in the high HCS group. At follow-up, cerebral palsy (35.9% vs. 9.1%, p = 0.003), neurodevelopmental impairment (54.0% vs. 23.6%, p = 0.002), and head circumference <10th percentile (64.3% vs. 19.5%, p < 0.001) were more common in the high HCS group. After adjustment, HCS > 90 mg/kg remained independently associated with cerebral palsy (adjusted odds ratio [aOR] 5.44, p = 0.016) and reduced head circumference (aOR 4.45, p = 0.016). Conclusions: High cumulative HC exposure correlated with reduced brain volume at TEA and adverse neurodevelopmental outcomes at 24 months of age. Careful monitoring of dose and treatment duration is essential to balance therapeutic benefits against potential risks.

Intrathecal chemotherapy for management of immune effector cell-associated neurotoxicity syndrome (ICANS): A multi-center, real-world analysis of clinical outcomes

Disclosure: B. Seo: Eton Pharmaceuticals. M.L. Freedman: Eton Pharmaceuticals. I. Hoos: Eton Pharmaceuticals. D. Radosavljevic: Eton Pharmaceuticals. A. Christensen: Eton Pharmaceuticals.Background: Treatment of adrenal insufficiency in children requires precise hydrocortisone (HC) dosing. Since the discontinuation of Cortef oral suspension, oral dosing options for this population are limited. Current Endocrine Society guidelines for primary adrenal insufficiency suggest dosing as low as 8 mg/m2/day split into 3 doses. The guidelines also recommend against using a compound pharmacy. Precise HC dosing is important because adverse outcomes including adrenal crisis can result from too little HC. Too high HC dosing can also cause detrimental effects, including Cushinoid sequela. An HC oral solution (HOS) was developed to assist with dosing accuracy in children to prevent complications that may arise from under- or overdoing of HC in pediatric, adrenal insufficient patients. Objective: This study investigated if a novel HOS is bioequivalent to a known, FDA-approved, oral HC formulation, also designed for pediatric patients, hydrocortisone oral granules (HOG). Methods: A single-center, open-label, randomized, two-period, crossover, single-dose, bioequivalency study between 5 mg HOS, 1 mg/mL, and 5 mg HOG in dexamethasone (DM)-suppressed healthy adults was conducted. Subjects were administered 4 mg DM 10 hr prior to HC administration. Subjects also fasted for 10 hr prior to HC administration. PK blood draws were conducted over 13 hr, beginning at 1 hr prior to HC administration. PK variables were determined for measured HC using a non-compartmental approach. Subjects were randomized to one of two conditions. Subjects were administered a single dose of 5 mg HOS or HOG. After a 7-day washout, subjects were administered the other treatment. The 2 HC formulations were considered bioequivalent if the 90% CI of the baseline adjusted HC AUCt, AUCinf, and Cmax were within 80 - 125%. Results: 36 subjects were recruited and enrolled in the study. 34 subjects completed the study. 2 subjects were discontinued because of an AE (fever and COVID-19 infection, respectively). The mean differences were: • * AUCt difference was 97.6% (390.7 vs 395.8 hr*ng/mL HOS to HOG, respectively) • * AUCinf difference was 99.4% (456.5 vs 455.8 hr*ng/mL HOS to HOG, respectively) • * Cmax difference was 104.7% (158.6 vs 152.8 ng/mL HOS to HOG, respectively) The study drugs were generally well-tolerated by the healthy DM-suppressed, fasted subjects. There were no serious AEs. None of the AEs compromised the subject’s safety or impacted the study results. Conclusion: This study confirms that HOS and HOG are bioequivalent in DM-suppressed, healthy, fasted adult subjects. Overall, the study medications were well tolerated in this population.Presentation: Saturday, July 12, 2025

Abstract Disclosure: P. Seo: None. M.M. Rutter: None. M. Yau: None. The classical form of 11β-hydroxylase deficiency (11-β OHD) CAH is differentiated by severe hypertension due to the mineralocorticoid effect of deoxycorticosterone and hyperandrogenism. For children, the Endocrine Society recommends daily hydrocortisone (HC) at 10-15 mg/m^2/day in divided doses. As children grow, frequent biological and laboratory monitoring is needed for small-dose titrations of HC to optimize adrenal control. Oral HC tablets are not explicitly designed for children, necessitating splitting tablets or having pediatric-specific formulations compounded. This process makes it challenging to deliver consistent doses, particularly for amounts less than 5 mg. In late 2020, the US FDA approved a pediatric-specific HC formulation in oral granules, with doses as low as 0.5 mg. Objective To assess adrenal control in CAH on various formulations of HC, we retrospectively reviewed the medical records of two pediatric patients with 11-β OHD who had received different formulations of oral HC (solution, tablets, and oral granules) for up to 4.5 years. Methods We collected demographic, anthropometric, and pubertal data, laboratory results, and medication formulation and dosing over multiple time points during pediatric endocrine follow-up. Laboratory results included ACTH, androstenedione, plasma renin activity (PRA), deoxycorticosterone, and 11-deoxycortisol concentrations. Choice of HC oral formulations was based on family preference and provider recommendation. Results Patient 1 (27-53 mo) was initially prescribed HC solution at doses of 8.5 -14.3 mg/m^2/day and transitioned to granules at 41 mo at 11.7-14.6 mg/m^2/day. Adrenal control on HC solution and granules was similar on solution and granules with androstenedione of 31-56 ng/dl, PRA of 0.17-2.7 . ACTH peaked at 54.8 pg/mL at 38 mo But normalized over time. Androstenedione stayed within the normal range, while 11-deoxycortisol peaked at 232 ng/dL. PRA remained below normal, except at 41 mo. Patient 2 (5-39 mo) transitioned from HC solution at 18 mg/m^2/day to tablets at 16-19 mg/m^2/day at 9 mo and then to granules at 14 m.o. While on granules, HC doses decreased from 18.2 to 7.25 mg/m^2/day due to poor compliance. Until 30 mo, ACTH and androstenedione remained low, respectively at&amp;lt;6 pg/mL) and &amp;lt;10 ng/dL). PRA was consistently below the normal range, and 11-deoxycortisol spiked at 30 mo (2029 ng/dL) and androstenedione rose to 115 ng/dl at 39 mo. Changes in formulations were well tolerated. Conclusion The results indicate that adrenal control was influenced by factors beyond the formulation of HC. Variations in adrenal control were observed based on the dosage of HC relative to body surface area, with the total daily dose emerging as a primary determinant of adrenal regulation. Adherence with medication dosing and stressful blood draws may have contributed to poor adrenal control and should be explored further. Presentation: Monday, July 14, 2025

Disclosure: S. Reyes: None. G. Gupta: None. H. Aftab: None.Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have evolved into a staple in the management of diabetes. One of its mechanisms of action is a delayed gastric emptying and small bowel transit (2). As a result, the use of GLP-1 RAs has been noted to slow the absorption of oral drugs which can be challenging to recognize. We present a case of adrenal insufficiency (AI) on hydrocortisone (HC) and fludrocortisone while on GLP-1 RA. Case: A 63 yo female with DM II, ACTH-dependent Cushing’s disease s/p hypophysectomy with recurrent cyclic Cushing’s disease s/p bilateral adrenalectomy on chronic HC was admitted for an adrenal crisis. She had doubled her usual HC dose for the past 2 weeks and administered IM HC prior to admission but was hypotensive on arrival. Serum sodium wnl, potassium 3.2 mEq/L, TSH 7.52 uIU/mL, fT4 1.35 ng/dL. She was treated with IV HC and IV antibiotics. She was discharged on her usual home PO HC and fludrocortisone. She continued to have BP on the lower end of normal, weight gain, worsening glucose control, hyperpigmentation, and nausea. Her HC dose was appropriate for her weight and her symptoms raised the possibility of HC malabsorption. She tried prednisone but symptoms were unchanged. Labs sodium 132 mmol/L, potassium 5.4 mmol/L, cortisol 6.2 ug/dL, ACTH 74 pg/mL, and renin activity 2.1 ng/mL/hr. She had been on tirzepatide for 2 years and decision was made to discontinue tirzepatide for 1 month. Repeat sodium 136 mmol/L, potassium 4.4 mmol/L, cortisol 11.1 ug/dL, ACTH 60.9 pg/mL and renin activity of 0.1 ng/mL/hr. She was restarted on tirzepatide but at a lower dose. Discussion: The results were suggestive of AI despite maintaining consistent intake of HC and fludrocortisone. There is limited data on drug-drug interactions between GLP-1 RA and other oral medications but we considered the possibility of the use of high-dose tirzepatide impacting absorption of HC. This has previously been observed however the GLP-1 RA used was exenatide (1). It also has been reported that GLP-1 RA can delay the absorption of dexamethasone (2). Our patient had improvement of all of her labs after discontinuation. This case highlights the utility of discontinuing a GLP-1 RA when there is a clinical suspicion of AI. (1)Fujita Y, Kitamura T, Otsuki M, Tamada D, Tabuchi Y, Kozawa J, Yasuda T, Okita K, Imagawa A, Kaneto H, Funahashi T, Shimomura I. Exenatide alters absorption of hydrocortisone in a diabetic patient with panhypopituitarism: iatrogenic adrenal insufficiency. Diabetes Care. 2013 Jan;36(1):e8. doi: 10.2337/dc12-1499. (2) Nagai Y, Mukai K, Otsuki M, Kimura T, Kozawa J, Nishizawa H, Maeda N, Matsuoka TA, Iwahashi H, Imagawa A, Shimomura I. Suppression Failure of Cortisol Secretion by Dexamethasone May Occur in Glucagon-like Peptide-1 Receptor Agonist-treated Patients with Diabetic Autonomic Neuropathy. Intern Med. 2019 Apr 1;58(7):949-953. Epub 2018 Dec 18.Presentation: Sunday, July 13, 2025

Disclosure: D.P. Merke: Research funding from Diurnal Limited, Neurocrine Biosciences, Inc., and Adrenas Therapeutics, and the National Institutes of Health Cooperative Research and Development Agreements, Received royalties from UpToDate for writing and editing. E.A. Imel: Consulting and clinical trial research funds from Neurocrine Biosciences, Inc., Clinical trial research funds from Spruce Biosciences. A. German: None. H. Falhammar: None. N. Reisch: Consulted for Neurocrine Biosciences, Inc., Spruce Biosciences, H Lundbeck A/S, Crinetics Pharmaceuticals and Diurnal Limited. L. Keener: None. J. Sturgeon: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc. R.H. Farber: Full-time employee of Neurocrine Biosciences, Inc.Background: Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class medication that is FDA-approved as an adjunctive treatment to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In two phase 3 trials, crinecerfont significantly reduced excess androgens, enabling subsequent GC dose reduction in pediatric and adult patients with CAH. Objective: To analyze changes in androstenedione (A4) and reductions in GC doses while maintaining or improving A4 in subgroups of participants from the CAHtalyst™ Adult study (NCT04490915). Methods: Participants were randomized 2:1 to crinecerfont 100 mg BID or placebo for 24 weeks. GC doses were kept stable for 4 weeks to evaluate the impact on androgens, followed by a planned GC down-titration over 8 weeks to a target of 8-10 mg/m2/d in hydrocortisone (HC) equivalents. GC doses were then adjusted as needed during the last 12 weeks to achieve the lowest GC dose while maintaining or improving A4 relative to baseline (BL). Changes from BL in A4 at Week 4 and in GC dose at Week 24 were analyzed in the overall population and in subgroups categorized by: region (US, outside US), sex (male, female), body mass index (<30, ≥30 kg/m2); race (white, non-white); BL dexamethasone (yes, no); BL GC regimen (HC alone, synthetic GCs); BL GC dose (<20, ≥20 mg/m2/d HC equivalents); and BL A4 (≤ULN [upper limit of normal], >ULN; evaluated for A4 change only). Results: In 182 randomized participants (crinecerfont, n=122; placebo, n=60), mean A4 at BL was 620±729 ng/dL; mean GC dose was 17.6±4.9 mg/m2/d (32.3±9.3 mg/d). Least-squares (LS) mean changes at Week 4 indicated significant A4 reduction with crinecerfont but not placebo (-299 vs +45.5 ng/dL; LS mean difference [LSMD]: -345 ng/dL; p<0.0001 [key secondary endpoint]). LSMDs of the point estimates for A4 change at Week 4 favored crinecerfont over placebo in all subgroups; treatment difference for A4 change was lower in the BL A4 ≤ULN subgroup, as these participants were already in the normal range. At Week 24, LS mean percent changes in GC dose indicated significantly greater reduction with crinecerfont (while maintaining/improving A4) than with placebo (-27.3% vs -10.3%; LSMD: -17.0%; p<0.0001 [primary endpoint]). LSMDs of the point estimates for GC dose percent change at Week 24 favored crinecerfont over placebo in all subgroups. For both A4 and GC, subgroup analyses were consistent with the primary and key secondary endpoint results in the overall population. Conclusions: Crinecerfont was effective in enabling GC dose reductions while maintaining or improving A4 in adults with CAH across all subgroups analyzed. These results demonstrate that adults with CAH can derive the androgen-lowering and GC-lowering benefits of crinecerfont treatment regardless of sex, race, BMI, or pre-treatment A4 levels, GC dose, or GC regimen.Presentation: Monday, July 14, 2025

Disclosure: J.G. Kallet: None. W. Hover: None. A.D. Krein: None. J.L. Crooks: None. G.L. Kinney: None. M.F. Slovick: None. U. Christians: None. B. Schniedewind: None. S. Majka: None. M.T. McDermott: None. E.A. Regan: None.Adrenal insufficiency (AI) has multiple causes including: infection, injury, surgical removal of the adrenal gland, impairment of pituitary or hypothalamus, genetic disorders and autoimmune disease. It results in a wide range of symptoms that are sometimes only partially relieved by replacement of the hormone cortisol. Cortisol secretion is circadian and also produced in response to stress. Many patients continue to experience disabling symptoms including fatigue, confusion, weakness, and others, and remain at risk for adrenal crisis under current replacement strategies. Previous work has shown that there is significant individual variation in absorption and metabolism of hydrocortisone (HC). Pharmacokinetic studies show HC has an average half life of only 90 minutes. Methods: We studied 18 individuals with adrenal insufficiency, pre and post morning HC dose for a total of 5 hours, and measured saliva cortisone and plasma cortisol in each pre-dose, and 1, 2, 3, 4, 5 hours post usual AM dose. Diagnosis of AI was confirmed by medical record review. Usual HC dose was recorded. Samples were analyzed using a quantitative high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Results: Age range was 25-75, mean 51.2 (SD 15.7), sex: 4 males, 14 females. Six people reported that they were normally asymptomatic and 12 were symptomatic. AddiQoL = 100.1 (higher better) in the asymptomatic group and 75.5 in the symptom group, p=0.003. Morning dose was 10 mg for 10 people and 15 mg for 8. AddiQoL showed a non-significant trend to higher in the 15 mg group (90 vs 79). Both plasma cortisol and saliva cortisone showed distinct pattern over the time period with a peak at 1 hour post dose and steep decline by five hours post dose. Mean (SD) values for plasma cortisol of the time studied were T0 2.9 (4.4), T1 22.6 (5.4), T2 18.0 (5.7), T3 13.1 (5.3), T4 8.4 (4.4), 6.8 (7.2) mcg/dL. Correlation between plasma cortisol and saliva cortisone was high at 0.89, (p<0.0001). Of the 18 people, 11 had first morning cortisol levels below 1.0 mcg/dL, and four had levels above 5 mcg/dL. Discussion: Pre dose cortisol levels were very low in most of the adrenal insufficient people suggesting inadequate replacement during critical overnight hours. Plasma cortisol and saliva cortisone using mass spectrometry as a measurement technique are highly correlated and offer a means to monitor replacement hormone in symptomatic patients. There is large variation in the pattern of absorption and metabolism of cortisol between people that may result in inadequate symptom control. Some AI patients may have residual secretion of cortisol allowing them to be less symptomatic with lower doses of replacement. The established half-life of hydrocortisone dosed twice a day does not provide a match to the normal circadian secretion and may result in both symptoms and increased risk of adrenal crisis.Presentation: Monday, July 14, 2025

Disclosure: V. Ramadoss: None. L. Cheong: None. L. Tan: None. P. Limumpornpetch: None. T. Puar: None. P. Eng: None.Objective: Adrenal insufficiency (AI) is a life-threatening endocrine disorder requiring timely diagnosis and management. This study aims to assess the burden, diagnostic approaches and management practices for AI across ASEAN nations, address unmet needs and improve outcomes through regional collaboration. Methods: A prospective, multicentre survey (October 2024–January 2025) was distributed to private and public healthcare providers by the ASEAN Network of Adrenal Hypertension (AnAH). The survey targets physicians managing AI across ten ASEAN countries. Lower-middle- (Indonesia, Philippines, Vietnam, Myanmar, Cambodia), upper-middle- (Malaysia, Thailand), and high-income nations (Singapore and Brunei) countries were included. Results: A total of 132 responses were received, with most from Cambodia (42.4%), Singapore (20.4%), Thailand (19.6%) and Vietnam (19.8%). Respondents were predominantly consultants (73.5%), 66.7% were endocrinologists, and 72.0% worked in public teaching hospitals. Common causes of AI included exogenous glucocorticoid-induced AI (87.1%), secondary AI (54.5%), AI due to infection or metastasis (32.6%), prior unilateral adrenalectomies (15.2%). Reported symptoms were fatigue (92.4%), nausea (59.8%), light-headedness (49.2%), gastrointestinal symptoms (37.9%), and hyperpigmentation (14.4%). Early morning cortisol was the preferred screening test (79.5%), but only 23.5% conducted paired cortisol and ACTH testing. Confirmation methods included a short Synacthen test (59%) or cortisol level (69.7%), while 11.4% relied solely on clinical symptoms.Definitions of AI varied, with 18.2% using a cut-off of <100nmol/L and 21.9% using a cut-off of <400 nmol/L. Hydrocortisone (HC) was the preferred treatment for AI crises, with 60.2% favouring bolus administration followed by divided doses, and 32% using continuous HC infusion. For maintenance, 60.2% prescribed HC (15–20 mg/day) in three doses, and 23.3% used prednisolone. Lack of Synacthen (49.2%) and consensus on diagnostic cut-offs (48.5%) were major barriers.In exogenous steroid-induced AI, 90.2% would wean steroid treatment, with weaning durations varied: 34.9% over 3-6 months, 25.6% over 12 months, 10.1% over 2 years. Only 70.7% of the physicians provided steroid emergency cards, and challenges included lack of educational resources (50%), poor patient understanding (91.7%), low healthcare provider awareness (54.5%). Patient adherence was rated higher for follow-up clinic visits (7/10) than for sick-day steroid dose adjustments (5/10). Conclusion: This study reveals significant variations in diagnosing and managing AI in ASEAN countries. Key gaps include inconsistent diagnostic criteria, limited availability of diagnostic tools, and inadequate patient and healthcare provider education. Addressing these gaps is essential to improving AI outcomes in the region.Presentation: Saturday, July 12, 2025

Disclosure: S.A. Mathara Diddhenipothage: None. J. Warden: None. K. Herbert: None. R. Pofi: None. N. Coupe: None. M. Payne: None. J.W. Tomlinson: None. H.E. Turner: None.Introduction: Acute Hypophysitis (Hp) is a serious adverse effect of Immune checkpoint inhibitor (ICI) therapy. Methods: Retrospective audit of all patients with ICI-Hp (n=22) referred to a dedicated Endocrine-ICI clinic (January 2017- Oct 2024), to determine clinico-radiological characteristics, features to flag for early diagnosis, treatment outcomes and recovery of hormonal axes. Results: Onset 13 w (IQR 9,17), after a median of 3rd (IQR 3,4) cycle, 55% females, age 67 y (IQR 53,74). Metastatic melanoma 77%. 68% received Ipilimumab (Ipi) with Nivolumab, 5% Ipi alone, and 27% anti PD-1 monotherapy. Majority (91%) were symptomatic; headache (64%), fatigue (77%), nausea (64%), vomiting (23%), anorexia (23%); hyponatremia 41%: mild (Na+ 130-135 mmol/L) 35%, severe (<125 mmol/L) 12%. All had acute secondary hypocortisolism (SHC); morning cortisol <100 nmol/L (82%) and <50 nmol/L (59%). Secondary hypothyroidism (SH) in 41%. Low prolactin (PRL) (<110 mIU/L) 32%: undetectable (<13 mIU/L) n=3: onset preceded SHC by 2 w (n=1). High PRL (446-1119) n=23%. Secondary hypogonadism (SHG) in 27%; onset preceded SHC by 11 w (n=1). Pituitary imaging ≤13 w (n=20); enlarged gland 64%, thickened stalk 50% [thickness 2.8 mm (IQR 2,3.4)], supra-sellar extension 46%, mild optic chiasm compression n=3 (pituitary biopsy n=1: lymphocytic Hp). Asymptomatic pituitary enlargement (n=1) preceded SHC onset by 4 w. Non-pituitary metastases 18%. Treatment used different glucocorticoid (GCs) regimens; IV methylprednisolone (MPP)(n=4), prednisolone (n=8), dexamethasone (n=1), and hydrocortisone (HC) oral stress dose for 48 h (n=6). All symptoms recovered fully: 33% within 48h (No data n=4). Acute psychosis with IV MPP (n=1). Significant resolution of scan findings in all (n=14) at 15 w (IQR 13, 21). No recovery of SHC in those evaluated (n=13), at 3 m (n=3), 2 y (n=3), 3 y (n=4), 4 y (n=2), and 8 y (n=1). In those with SH, 33% recovered at 5 w (IQR 4,16) and no recovery in 44% on reassessment at 3 y (IQR 1,6). Recovery of SHG was seen in 67% at 10 w (IQR 7,16), whilst no recovery n=2 (3 y) Acute onset ICI-related type 1 diabetes (T1D) was common 18% (overall prevalence of ICI-T1D 0.6-1.4%), median onset 20 w (IQR 10, 54) of ICI, 3/4 presented with DKA. Cancer progression free survival 59% [3 y (IQR 1, 6)]. Mortality 14% [3 y (2,6)]. Treatment with high dose GCs not associated with cancer progression (p=0.674), or mortality (p=0.544). Conclusions: Acute ICI-Hp is a heterogenous clinical entity. However, important practice points highlighted to improve care; 1. Raised awareness for symptom safety netting recommended for Ipi based therapy particularly after 3rd cycle; 2. SH, SHG and low PRL may precede SHC; 3. GCs useful for symptom control but higher dose had no effect on disease course and may increase adverse effects; 4. Recovery of SH and SHG should be actively sought during follow up; 5. ICI related T1D may be more commonly associated with ICI-Hp.Presentation: Saturday, July 12, 2025

The biological activity of steroidal compounds such as dexamethasone (DX) and hydrocortisone (HC) is closely linked to subtle variations in their molecular structure and electronic properties. This study provides a comparative quantum chemical analysis of DX and HC to clarify how these differences influence hydrogen bonding strength, reactivity, and their potential interactions with the glucocorticoid receptor (GR). Optimized geometries, natural bond orbital (NBO) analyses, frontier molecular orbitals (FMO), global reactivity descriptors, and average local ionization energy (ALIE) calculations demonstrate that DX exhibits greater polarity and electrophilic character compared to HC. These differences help explain the stronger receptor binding affinity observed for DX. Indeed, notably, despite the inherent limitations of gas-phase DFT calculations compared to experimental X-ray data, the theoretical results exhibit good agreement with experimental observations, suggesting the reliability of the computational approach in predicting molecular interactions within the GR active site. All quantum chemical calculations were performed using density functional theory (DFT) with the B3LYP functional and 6-311++G(d,p) basis set. Structural optimization, FMO analysis, global reactivity descriptors, and dipole moment evaluations were carried out in Gaussian 09. NBO analysis was performed with NBO 5.0. Average local ionization energy (ALIE) surfaces were generated using Multiwfn 3.8, and molecular visualizations were produced with GaussView 5.0.

Association between total hydrocortisone dose and neurodevelopmental outcome at 3years old in newborns under 28weeks of gestation.

An association between total hydrocortisone (HC) dosage in infants with extremely low birth weight (ELBW) and subsequent neurodevelopmental outcomes up to school age remains unclear. We conducted a retrospective longitudinal cohort study across eight centers in Japan, including ELBW infants born between 2015 and 2017. We investigated the association between total HC dosage administered up to 36 weeks postmenstrual age and neurodevelopmental outcomes to school age. Linear mixed model analysis showed a significant association between higher HC dosage and lower developmental and intelligence quotient (DQ/IQ) scores. This trend persisted at 6 years of age, suggesting a sustained effect of HC on cognitive outcomes. For every 10 mg increase in HC dosage, IQ scores decreased by 2.82 points (95% CI: -3.89 to -1.06, p = 0.001). The interaction term between HC dosage and time was not statistically significant (0.10, 95% CI: -0.18 to 0.37, p = 0.481), suggesting the association of HC dosage on DQ/IQ did not vary substantially throughout the study period. We found a relationship between total neonatal HC dosage in ELBW infants and DQ/IQ scores over time that persisted at school age. Clinicians should be aware of this potential dose-dependent effect on neurodevelopmental outcomes. As neonatal dexamethasone administration is known to affect neurodevelopment outcomes, hydrocortisone (HC) is considered an alternative to dexamethasone as a glucocorticoid treatment. In infants with extremely low birth weight (ELBW), a relationship has been noted between total HC dosage and neurodevelopment in early childhood. We confirmed the association between total HC dosage in infants with ELBW and poor developmental and intelligence quotients to school age. Although HC is commonly used in the management of ELBW infants, clinicians should be aware of its potential dose-dependent effects on neurodevelopmental outcomes.

The role of Atp2a2-mediated calcium imbalance and endoplasmic reticulum stress in hydrocortisone-induced neurotoxicity