Introduction: Adrenal insufficiency (AI) is a life-threatening condition that frequently presents with non-specific symptoms, complicating early diagnosis. Morning serum cortisol serves as an effective initial screening tool for assessing the hypothalamic-pituitary-adrenal (HPA) axis, potentially reducing the necessity for dynamic investigations such as the Short Synacthen Test (SST). This study aims to assess the clinical indications for morning cortisol testing and evaluate institutional compliance with guideline-based cortisol cut-offs, the initiation of hydrocortisone therapy, and the provision of “sick day” education. Methodology: A retrospective cross-sectional study was conducted among inpatients at a tertiary hospital in Central Pahang who underwent morning cortisol evaluation between March and August 2025. Data regarding demographics, indications, biochemical results, and clinical management were analyzed using SPSS version 26.0. Results: Among the 111 patients included (mean age: 54.96 ± 15.88 years), the primary indications for testing were hyponatremia (54.1%), hypotension (27.9%), and a history of traditional medication use (26.1%). Based on Endocrine Society guidelines: <150 nmol/L (AI likely): 16.2%, 150–300 nmol/L (Borderline): 26.1%, and >300 nmol/L (AI unlikely): 57.7%. Notably, only 10 of the 18 patients with cortisol levels <150 nmol/L were formally diagnosed and initiated on appropriate therapy. In the borderline group, only two patients underwent an SST. Although 12 patients overall were treated for AI, only eight received documented “sick day” education. Low cortisol levels were significantly associated with hyponatremia, hypotension, and traditional medication use, and demonstrated a negative correlation with serum sodium and albumin levels. Conclusion Morning serum cortisol is a valuable screening tool for AI, particularly in patients presenting with hyponatremia or hypotension. However, significant gaps persist in follow-up management, confirmatory testing, and patient education. Implementing standardized protocols and enhancing clinician education are essential to optimize care.
Hydrocortisone ; Adrenal Insufficiency ; Tertiary Care Centers

Introduction: Cushing’s syndrome is a multisystem disorder with significant cardiovascular morbidity, yet presentation as acute heart failure is uncommon. When driven by adrenocortical carcinoma (ACC), the clinical course is often aggressive and rapidly fatal, with particularly poor out-comes in resourcelimited settings where access to therapy is constrained. Case: A 39-year-old previously well female presented with acute decompensated heart failure, newly diagnosed hypertension, type 2 diabetes mellitus, and obesity, preceded by a 3-year history of secondary amenorrhea and progressive weight gain. On admission, she exhibited florid Cushingoid features. Biochemical evaluation confirmed severe adrenocorticotropic hormone (ACTH)-independent hypercortisolism: morning serum cortisol 1,950 nmol/L, failure of suppression on overnight dexamethasone suppression test (post-ODST cortisol 2022.9 nmol/L), and elevated 24-hour urinary free cortisol (2,069 nmol/24 hours, 2.56 × upper limit of normal). Androgen excess was evident, with elevated dehydroepiandrosterone sulfate (DHEAS more than 27 µmol/L) and testosterone (9.91 nmol/L). ACTH was suppressed, supporting an adrenal source, while aldosterone was normal. Contrast-enhanced computed tomography demonstrated a large left adrenal mass (12 cm) with tumor thrombus extending into the inferior vena cava and renal veins, with extensive hepatic and pulmonary metastases, consistent with advanced ACC. Management was limited by disease severity and resource constraints. Ketoconazole was contraindicated due to transaminitis, and alternative steroidogenesis inhibitors were unavailable, leaving metyrapone as the only feasible option. Oncological therapy was deferred due to sepsis and clinical instability. Her course was fulminant, complicated by recurrent heart failure, sepsis, and metabolic derangements, culminating in refractory cardiopulmonary failure. She died within 1 month of diagnosis, prior to definitive oncological intervention. Conclusion Fulminant cortisol-secreting ACC may present catastrophically as acute heart failure and progress rapidly. Early recognition and timely access to multimodal cortisollowering therapy are critical, particularly in resourcelimited settings. In fulminant hypercortisolism, the challenge is not diagnosis—but timing.
Adrenocortical Carcinoma ; Hydrocortisone ; Heart Failure

Introduction: Pituitary apoplexy is an acute endocrine emergency, as early recognition may influence the outcomes, often presenting with sudden headache, visual disturbances, ocular palsies, vomiting, or altered consciousness. Given that urgent surgical decompression is a common management, emerging evidence supports corticosteroid therapy in our patient with significant neuro-ophthalmic deficits. Case: A 65-year-old male with hypertension, dyslipidemia, type 2 diabetes mellitus, chronic kidney disease stage III, and ischemic heart disease presented with a 4-day history of fever, vomiting, bifrontal headache, and generalized abdominal pain. Initially, he was treated for presumed intraabdominal sepsis. On day 3 of admission, he developed acute right-sided complete ptosis with ophthalmoplegia involving cranial nerves III, IV, and VI. Prior to that, he had also reduced morning erections for 6 months before presentation. Biochemical evaluation revealed markedly reduced total testosterone (0.33 nmol/L) with inappropriately low–normal gonadotropins (luteinizing hormone 1.5 IU/L, follicle-stimulating hormone 2.3 IU/L), in keeping with secondary hypogonadism. Adrenocorticotropic hormone was suppressed, indicating secondary adrenal insufficiency. Thyroid function was preserved. Overall findings suggested partial hypopituitarism. Magnetic resonance imaging confirmed a cystic pituitary lesion measuring 1.4 × 2.6 × 1.8 cm with cavernous sinus involvement and features of pituitary apoplexy. His Pituitary Apoplexy Score was 4. He was offered surgical intervention but was not keen. He was treated with intravenous hydrocortisone, with rapid clinical improvement, including near-complete resolution of right eye ptosis and restoration of extraocular movements within 3 days, and was able to recover without surgery. The hydrocortisone was gradually tapered, and the patient was discharged well with Endocrine follow-up. Conclusion Timely corticosteroid therapy alone can result in rapid, near-complete neurological recovery in pituitary apoplexy, even with multiple cranial nerves involvement. In carefully selected patients without visual field compromise, conservative management may safely obviate the need for urgent surgical intervention, emphasizing the importance of early recognition and individualized treatment strategies.
Hydrocortisone ; Pituitary Apoplexy

Empathy is crucial for communication and survival for individuals. Whether empathy in pain contagion shows sex differences and its underlying mechanisms remain unclear. Here, we report that pain contagion can occur in stranger female rats, but not in stranger males. Blocking oxytocin receptors in the anterior cingulate cortex (ACC) suppressed pain contagion in female strangers, while oxytocin administration induced pain contagion in male strangers. In vitro, corticosterone reduces neuronal activation by oxytocin. During male stranger interactions, higher corticosterone decreased oxytocin receptor-positive neuronal activity in the ACC, suppressing pain contagion. These findings highlight the role of oxytocin in pain contagion and suggest that sex differences in empathy may be determined by the balance of oxytocin and corticosterone in the ACC. This study suggests an approach for the treatment of certain mental disorders associated with abnormal empathy, such as autism and depression.
Animals ; Oxytocin/pharmacology* ; Gyrus Cinguli/drug effects* ; Male ; Female ; Corticosterone/pharmacology* ; Empathy/drug effects* ; Sex Characteristics ; Receptors, Oxytocin/antagonists & inhibitors* ; Pain/psychology* ; Rats ; Rats, Sprague-Dawley ; Neurons/metabolism*

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

INTRODUCTION

Administration of antenatal corticosteroids (ACS) between 24 and 36 weeks of gestation is recommended to pregnant women at risk of preterm delivery to decrease the risk of respiratory distress syndrome, intra-ventricular hemorrhage and neonatal death. However, it may worsen glycemic profile primarily in those with gestational diabetes mellitus (GDM).

To determine the effects of ACS on maternal glycemia in Filipino women with GDM and to analyze the factors associated with insulin use or increased insulin requirement.

A retrospective study of the medical records of Filipino women with GDM who were admitted and received ACS treatment (betamethasone) between 24- and 36-weeks age of gestation (AOG) for fetal lung maturity from 2017-2019. Clinical characteristics (age, parity, completed ACS dose, AOG at ACS administration and mode of delivery) and glycemic control were retrieved and compared before and after ACS treatment. Data collection began the day or on the day before steroids were given and continued until discharge or delivery.

Included were 42 pregnant women with GDM. Of these, 28 women with GDM were treated by diet alone (Group A) while 14 women with GDM were started on insulin in addition to diet (Group B). After betamethasone therapy was initiated, only three (Group A1; n=3/28) patients had good glycemic control with diet alone and the rest were given insulin treatment (Group A2; n=25/28). In this subpopulation of Group A2, insulin requirement within 24 hours after ACS was at 0.3 units per kg of body weight. There was a steady increase with maximum requirement observed on day 4 and decreased thereafter to 0.33 units per kg of body weight on day 5. For GDM women in Group B, only three maintained their insulin dose (Group B1; n=3/14) while 11 (Group B2; n=11/14) women with GDM previously on insulin, required further increase in insulin from day 1-2 reaching 140% increase in insulin dose on day 2. Thereafter, there was a gradual decrease of insulin dose almost returning to initial dose on day 5.

Insulin initiation was observed among GDM diet-controlled mothers (Group A) who were given ACS therapy at ≥31 weeks age of gestation. Age, parity, family history of diabetes and mode of delivery did not have significant effects on insulin use nor increased insulin requirement. Fasting capillary glucose (FCG) and one-hour post-prandial capillary glucose (PPCG) were elevated within 24 hours after administration of corticosteroid (betamethasone) in 60%-70% of our population. The FCG values remained elevated on day 2-3 in about 70% of patients. While the first hour PPCG was elevated in 85% of patients on day 2 and remained elevated in 70% of women on day 3-4, it reached 53% on day 5. Insulin requirement among Group B2 reached to 140% increase in insulin dose on day 2 followed by a gradual decrease of insulin dose almost returning to initial dose on day 5.

ACS administration caused maternal hyperglycemia in Filipino women with GDM during the first 24 hours and lasting up to five days. Both fasting glucose and post-prandial glucose were elevated, hence intensified monitoring of maternal glucose levels and temporary addition or increase of insulin doses may be necessary. The timing (≥31 weeks AOG) of administration of ACS on GDM women was associated with subsequent insulin initiation but only on patients initially controlled on diet alone.

OBJECTIVE

This study determined the incidence of perioperative complications associated with routine preoperative glucocorticoid use in patients undergoing pituitary surgery with normal preoperative hypothalamo-pituitary-adrenal axis (HPA axis).

From 2011-2021 retrospective chart review, 243 patients undergoing pituitary surgery with normal preoperative HPA axis were analyzed into 2 groups: 1) with preoperative steroids and 2) without preoperative steroids.  Development of postoperative complications was subsequently evaluated.

Incidence of primary composite postoperative complications of in-hospital mortality, postoperative infection and postoperative diabetes insipidus (DI) was significantly increased among those who had preoperative steroids compared to those without (58.33% versus 33.33%, p-value 0.004)  with an adjusted odds ratio of 2.90 (CI 1.29 to 6.53, p-value 0.010). Among the components of the composite outcome, post-operative DI was statistically higher among those who were given preoperative steroids (52.45% versus 28.21%, p-value 0.006) with an adjusted OR of 3.31 (CI 1.43 to 7.67, p-value 0.005). The incidence of postoperative adrenal insufficiency was similar between the 2 groups (20.15% with steroids versus 8.70% without steroids, p-value 0.258).

Among patients with normal preoperative HPA axis, the routine use of preoperative steroids is associated with an increased risk of composite postoperative complications (in-hospital mortality, postoperative infection and postoperative DI). Steroid-sparing protocol is not associated with an increased risk of postoperative AI. The findings will encourage more rational use of steroids and minimize preventable complications.

IgG4-related disease （IgG4-RD） is an idiopathic fibroinflammatory condition characterized by a predilection for tumor-forming lesions， an increase in the serum level of IgG4， excessive infiltration of IgG4-positive plasma cells， storiform fibrosis， and/or obliterative phlebitis. This article reports a rare case of IgG4-RD in which the patient developed recurrent transient ischemic attacks （TIA） after the diagnosis of IgG4-RD. This report explores the potential pathological mechanisms， clinical features， treatment， and prognosis of IgG4-RD with TIA， in order to enhance the awareness of the possible neurological complications associated with IgG4-R among clinicians.
Glucocorticoids

Steroid-induced osteonecrosis of femoral head (SONFH) is a disease characterized by femoral head collapse and local pain caused by excessive use of glucocorticoids. Peroxisome proliferator-activated receptor-γ (PPARγ) is mainly expressed in adipose tissue. Wnt/β-catenin, AMPK and other related signaling pathways play an important role in regulating adipocyte differentiation, fatty acid uptake and storage. Bone marrow mesenchymal cells (BMSCs) have the ability to differentiate into adipocytes or osteoblasts, and the use of hormones upregulates PPARγ expression, resulting in BMSCs biased towards adipogenic differentiation. The increase of adipocytes affects the blood supply and metabolism of the femoral head, and the decrease of osteoblasts leads to the loss of trabecular bone, which eventually leads to partial or total ischemic necrosis and collapse of the femoral head. MicroRNAs (miRNAs) are a class of short non-coding RNAs that regulate gene expression by inhibiting the transcription or translation of target genes, thereby affecting cell function and disease progression. Studies have shown that miRNAs affect the progression of SONFH by regulating PPARγ lipid metabolism-related signaling pathways. Therefore, it may be an accurate and feasible SONFH treatment strategy to regulate adipogenic-osteoblast differentiation in BMSCs by targeted intervention of miRNA differential expression to improve lipid metabolism. In this paper, the miRNA-mediated PPARγ-related signaling pathways were classified and summarized to clarify their effects on lipid metabolism in SONFH, providing a theoretical reference for miRNA targeted therapy of SONFH, and then providing scientific evidence for SONFH precision medicine.
MicroRNAs/physiology* ; PPAR gamma/metabolism* ; Femur Head Necrosis/metabolism* ; Humans ; Signal Transduction/physiology* ; Lipid Metabolism/physiology* ; Animals ; Cell Differentiation ; Mesenchymal Stem Cells/cytology* ; Glucocorticoids/adverse effects*