Introduction: Large, rapidly enlarging adrenal masses typically mandate surgical intervention given the high probability of adrenocortical carcinoma (ACC). However, benign processes can mimic these aggressive growth kinetics, creating a diagnostic challenge for clinicians. Case: A 74-year-old male with hypertension, atrial fibrillation on rivaroxaban, and prostate cancer was referred for evaluation of a right adrenal incidentaloma detected on computed tomography imaging performed for prostate cancer staging. The well-defined mass measured 8.9 × 7.8 × 7.5 cm (AP × W × CC) with areas of calcification. Mean attenuation was +40 Hounsfield Unit, with no significant washout. Biochemical evaluation confirmed a non-functioning lesion (24-hour urine metanephrines 756 mcg/24 hours [N 246–753 mcg/24 hours]; serum cortisol 62 nmol/L post overnight dexamethasone suppression test). The patient was otherwise asymptomatic and declined surgical intervention. Repeat imaging 4 months later demonstrated interval enlargement of the mass to 9.8 × 8.8 × 10.7 cm. Due to this rapid growth, which was highly concerning for ACC, the patient underwent laparoscopic right adrenalectomy. Histopathological examination unexpectedly revealed an adrenal hematoma without evidence of an underlying tumor or malignancy. This case illustrates the difficulty in differentiating aggressive cortical tumors from atypical hemorrhagic events. Larger series on adrenal hemorrhage reported trauma and procedural complications as the leading causes, with a median size of 3–4 cm. Idiopathic large adrenal hematomas presenting as rapidly expanding “pseudotumors” are exceptionally rare, with fewer than 20 cases reported in which surgical resection was performed due to high preoperative suspicion of malignancy. Additionally, adrenal hemorrhage attributed to anticoagulant therapy often occurs bilaterally. Unilateral lesion, especially when large, can pose a diagnostic challenge as highlighted in this case. Conclusion In patients on anticoagulation, rapid interval growth of an adrenal mass does not always equate to malignancy. Recognizing this mimicry in the era of widespread Direct Oral Anticoagulant use is essential for refining treatment decision regarding surgical intervention, as most cases exhibited a self-limiting process with spontaneous resolution.

Introduction: The increasing prevalence of diabetes represents a significant global health challenge. Modifiable risk factors, including physical inactivity, unhealthy dietary habits, and obesity contribute substantially to this rising burden. In conjunction with the 2025 World Diabetes Day (WDD) campaign focusing on “diabetes and the workplace,” we assessed diabetes risk among healthcare workers in our hospital using the Modified Asian Finnish Diabetes Risk Score (ModAsian FINDRISC). Methodology: Healthcare workers from various departments were invited to participate in the hospital WDD celebration. A total of 286 attendees underwent anthropometric measurements and completed the ModAsian FINDSRIC questionnaire. Descriptive statistics were used to summarize the prevalence of risk factors and overall diabetes risk. Results: The participants included doctors, nurses, allied healthcare professionals, as well as hospital support and administrative staff. The majority of participants (74.8%) were aged below 45 years. 39.2% were overweight while 30.8% were obese. One-third (37.4%) had increased waist circumference (WC) (≥90 cm for men, ≥80 cm for women). Additionally, 20% of respondents reported being on antihypertensive medication, and 23.8% had previously recorded high blood glucose. A family history of diabetes mellitus (DM) was reported by 62.6% of respondents. Additionally, about onethird were sedentary with less than 30 minutes of daily exercise or physical activity, another one-third did not consume fruits or vegetables on a daily basis. The median ModAsian FINDRISC score was 8, with approximately 30% of them classified as having moderate to very high risk of developing DM (moderate: 17.5%; high: 10.8%; very high: 2.8%). Conclusion These results revealed high metabolic risk in healthcare workers and highlight the need for targeted workplace health promotion strategies to reduce the risk of developing diabetes.
Tertiary Care Centers ; Health Personnel ; Diabetes Mellitus

Introduction: Repaglinide, a meglitinide analogue, has a rapid onset and short duration of action. It offers prandial glucose control while reducing hypoglycemia risk compared to sulfonylureas. We describe its use in our special cohorts of diabetic patients where repaglinide was prescribed to reduce hypoglycemia in vulnerable patients or to optimize glycemic control through pharmacotherapy intensification or deintensification. Cases: Cohort A comprised 12 elderly patients with multiple comorbidities (mean age: 70.3 years; mean DM duration: 18.3 years) characterized by high glucose variability and problematic hypoglycemia. In seven patients, low-dose gliclazide was replaced with repaglinide with reduction in hypoglycemic episodes. One patient on low-dose premixed insulin was successfully switched to preprandial repaglinide. Two patients on basal insulin were able to reduce their insulin requirements and stabilize their glucose levels. A younger patient with autonomic dysfunction had hypoglycemia while on insulin glulisine, while its omission led to severe hyperglycemia. Substituting glulisine with repaglinide resolved the glucose variability. Repaglinide effectively reduced hypoglycemic episodes while maintaining glycemic stability, with a mean hemoglobin A1c (HbA1c) reduction of 0.36% over 3–6 months. Cohort B consisted of six younger patients (mean age: 35.3 years) with focus on optimizing HbA1c and improving treatment adherence. Two patients on basal-bolus regimes success-fully transitioned off bolus insulin to repaglinide, significantly improving compliance. One patient on basal insulin was successfully transitioned to an all-oral regimen. Three patients on existing oral hypoglycemic agents were started on repaglinide to close the glycemic gap. Cohort B achieved a robust mean HbA1c reduction of 2.1% within 3–6 months. Conclusion Repaglinide remains an important armamentarium in personalized diabetes management. Its pharmacokinetics and flexible dosing allow intensification of glycemic control while minimizing the risk of hypoglycemia. It also offers a viable strategy for selected patients struggling with complex insulin regime.
Repaglinide

Introduction: Severe hypercalcemia is most commonly caused by primary hyperparathyroidism (PHPT) and malignancy. While standard therapies are effective in most cases, a subset of patients have persistent or refractory hypercalcemia. We present a retrospective case series detailing the clinical characteristics, biochemistry, and outcomes of patients treated with denosumab for hypercalcemia. Cases: Seven patients with severe hypercalcemia were identified, comprising five with PHPT and two with malignancyassociated hypercalcemia. The mean age was 70.4 years (range 55–86), with 71% female (n = 5) and 29% male (n = 2). Baseline corrected calcium ranged from 2.92 to 4.59 mmol/L, with a mean of 3.26 mmol/L. In the PHPT cohort, parathyroid hormone (PTH) levels were significantly elevated (16.7–168 pmol/L), while malignancy patients had suppressed PTH (0.6 and 0.9 pmol/L). Prior to denosumab, 4/7 patients (57%) received bisphosphonates, 3/7 (43%) received calcitonin, and 1/7 (14%) was treated with cinacalcet. Denosumab resulted in a mean reduction in corrected calcium of 0.22 mmol/L from 3.26 to 3.03 mmol/L. Biochemical response was observed in 5/7 patients (71%). Of these, 3 patients (43%) achieved normocalcemia, while 2 patients (29%) demonstrated a partial response. The remaining 2/7 patients (29%) showed no significant improvement in calcium levels. Among responders, the mean time to calcium reduction to <3.0 mmol/L was 27 days (range 7–47). Repeat dosing was required in the majority of patients, with a mean of 1.7 doses per patient (range 1–4), indicating variability in both onset and durability of response. Among patients with PHPT, four underwent parathyroidectomy, and one declined surgery. Both patients with malignancy were managed nonsurgically. Conclusion Denosumab achieved normocalcemia in 43% of patients, with additional partial responses. Its effects were variable, with delayed response and frequent need for repeat dosing, supporting its role as an adjunctive or bridging therapy rather than as a definitive treatment.
Denosumab ; Hypercalcemia ; Retrospective Studies

Introduction: Hypercalcemic crisis, a decompensated state characterized by multiorgan dysfunction and a corrected serum calcium (CCa) level typically >3.5 mmol/L, is a rare but lifethreatening endocrine emergency that requires prompt recognition and aggressive multimodal management. We report a fatal case of hypercalcemic crisis secondary to primary hyperparathyroidism, which was refractory to multiple lines of medical therapy. Case: A 55-year-old female with diabetes mellitus, hypertension, and chronic kidney disease (creatinine 159 umol/L; estimated glomerular filtration rate 33 mL/min) presented with 3 days of confusion, profound fatigue, and constipation, preceded by a 1-month history of polyuria and polydipsia. Her Glasgow Coma Scale (GCS) was E4V3M5. Physical examination was unremarkable, with no palpable neck swelling. Significant laboratory findings included severe hypercalcemia with markedly elevated serum intact parathyroid hormone (iPTH) (CCa 4.49 mmol/L; phosphate 1.01 mmol/L; iPTH 60.1 pmol/L [N 1.6–6.0]; creatinine 149 umol/L). Saline diuresis was initiated together with subcutaneous calcitonin, resulting in an initial biochemical response, with CCa decreasing to a nadir of 3.61 mmol/L. However, the CCa subsequently rebounded to 5.00 mmol/L. Hemodialysis was performed, followed by administration of subcutaneous denosumab 60 mg. Nonetheless, the CCa decreased only modestly to 4.28 mmol/L. She became increasingly drowsy, and her clinical course was further complicated by aspiration pneumonia and lung collapse, leading to respiratory failure requiring intubation and inotropic support. Despite intensive care, additional sessions of hemodialysis and continuous renal replacement therapy, her CCa remained persistently above 4.0 mmol/L, peaking at 5.35 mmol/L. Due to her critical condition, imaging for lesion localization could not be performed. She eventually succumbed to her illness on day 10 of admission, before definitive surgery could be undertaken. Conclusion This case highlights the potentially fatal course of hypercalcemic crisis secondary to primary hyperparathyroidism. The reported mortality rate is high, at around 60%. Early recognition and intensive management, including emergency parathyroidectomy in resistant cases, have been shown to be crucial in improving outcomes.
Hyperparathyroidism, Primary

Introduction: Ectopic ACTH secretion (EAS) is a rare cause of Cushing’s syndrome, accounting for 5–15% of cases. Pulmonary neuroendocrine tumors are the most frequent cause. However, primary tumor localization remains a significant diagnostic challenge, delaying effective treatment. Case: A 59-year-old female with diabetes mellitus presented with refractory hypertension and hypokalemia. Initial laboratory findings revealed a baseline cortisol of 1,164 nmol/L and morning adrenocorticotropic hormone (ACTH) of 19.5 pmol/L (normal <10.2 pmol/L), with an overnight dexamethasone suppression test cortisol of 624 nmol/L. Pituitary magnetic resonance imaging (MRI) and computed tomography (CT) scans of the thorax, abdomen, and pelvis were initially unremarkable. A PET scan identified mild hypermetabolism in the left adrenal gland and gastrointestinal tract, though colonoscopy revealed only chronic colitis. An intravenous desmopressin stimulation test demonstrated a 181% rise in ACTH and a 35% rise in cortisol, pointing toward pituitary Cushing’s. However, repeat pituitary MRI remained normal. A high-dose dexamethasone suppression test showed approximately 34% cortisol suppression (cortisol 1,128 nmol/L to 745 nmol/L), suggesting ectopic Cushing’s syndrome. Bilateral inferior petrosal sinus sampling demonstrated a peak central-to-peripheral ACTH ratio of 1.8 on the right and 1.6 on the left, pointing toward ectopic Cushing’s. Localization with DOTATATE PET-CT identified a 7 × 9 × 8 mm nodule in the right middle lobe. A wedge resection was performed. Histopathology confirmed a typical carcinoid tumor with clear resection margins. Immunohistochemistry revealed tumor cells positive for CK AE1/ AE3, synaptophysin, chromogranin, and INSM-1, with weak positivity for ACTH. The latest 8 am cortisol was 117 nmol/L and ACTH 1.74 pmol/L, confirming biochemical cure. Hypokalemia resolved, with improvement in her metabolic profile. Conclusion This case highlights the diagnostic complexities of EAS, particularly when initial imaging is inconclusive and biochemical tests yield conflicting results. Timely, precise localization of the causative tumor is crucial for successful surgical intervention and to prevent severe complications of hypercortisolism, thereby improving patient outcomes.
ACTH Syndrome, Ectopic

Introduction: Electrolyte imbalance is common in central nervous system infections. Arginine vasopressin deficiency (AVP-D), Cerebral Salt Wasting (CSW), and Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) are important etiologies that can cause opposing extremes of serum sodium, posing diagnostic and therapeutic challenges. We report a rare case of transient central AVP-D followed by CSW secondary to tuberculous meningitis (TBM). Case: An 18-year-old female presented with a 1-month history of fever, reduced responsiveness, and visual hallucinations. Her Glasgow Coma Scale was E4V1M4 with neck stiffness and upper motor neuron signs. Initial investigations revealed severe hyponatremia (119 mmol/L) and communicating hydrocephalus with third ventricle ballooning on brain imaging. Coupled with a positive tuberculosis contact, anti-tuberculous therapy was initiated for probable TBM alongside 3% saline correction prior to insertion of external ventricular drain (EVD). Her condition deteriorated on day 5, requiring intubation for aspiration pneumonia. Repeated imaging showed worsening hydrocephalus, necessitating EVD revision. She subsequently developed polyuria (urine output [UO] 150–300 mLs/hour), with biochemical findings consistent with AVP-D (serum sodium 154 mmol/L; urine osmolality 96 mOsm/kg; urine sodium <20 mmol/L). Intravenous desmopressin 1 mcg was administered, and UO reduced to 30 mLs/hour. However, polyuria recurred on Day 9, accompanied by tachycardia, hypotension, and a rapid decline in serum sodium to 120 mmol/L. Diagnosis of CSW was established (urine sodium 204 mmol/L; urine osmolality 470 mOsm/kg). Oral fludrocortisone was initiated and titrated to 0.4 mg daily to maintain serum sodium >130 mmol/L. Due to persistent hydrocephalus, right ventriculoperitoneal shunt was inserted on Day 22, after which her UO gradually decreased, allowing tapering of fludrocortisone. She remains on fludrocortisone 0.1 mg daily with ongoing rehabilitation. Conclusion TBM can be complicated by SIADH, AVP-D, or CSW. Concurrent AVP-D and CSW have not been reported. This case highlights the dynamic electrolyte disturbances in TBM which may lead to diagnostic confusion and therapeutic error. Early recognition and tailored therapy, alongside definitive management to reduce intracranial pressure, are essential for optimal outcomes.
Hypernatremia ; Hyponatremia ; Tuberculosis, Meningeal

AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.

OBJECTIVE: To investigate the mechanism of induction of ferroptosis by brazilin in breast cancer cells. METHODS: Breast cancer 4T1 cells were divided into 6 groups: control, brazilin 1/2 half maximal inhibitory concentration (IC₅₀), IC₅₀, 2×IC₅₀, erastin (10 µg/mL) and capecitabine (10 µg/mL) groups. The effect of brazilin on the proliferation of 4T1 cells was detected by cell counting kit-8 assay, and the treatment dose of brazilin was screened. The effect of brazilin on the mitochondrial morphology of 4T1 cells, and the mitochondrial damage was evaluated under electron microscopy. The levels of Fe²⁺, reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH) and glutathione peroxidase 4 (GPX4) were estimated using various detection kits. The invasion and migration abilities of 4T1 cells were detected by scratch assay and transwell assay. The expressions levels of tumor protein p53, solute carrier family 7 member 11 (SLC7A11), GPX4 and acyl-CoA synthetase long-chain family member 4 (ACSL4) proteins were quantified by Western blot assay. RESULTS: Compared to the control group, the 10 (1/2 IC₅₀), 20 (IC₅₀) and 40 (2×IC₅₀) µg/mL brazilin, erastin, and capecitabine groups showed a significant decrease in the cell survival rate, invasion and migration abilities, GSH, SLC7A11 and GPX4 protein expression levels, and mitochondrial volume and ridge (P<0.05), and a significant increase in the mitochondria membrane density, Fe²⁺, ROS and MDA levels, and p53 and ACSL4 protein expression levels (P<0.05). CONCLUSIONS Brazilin actuated ferroptosis in breast cancer cells, and the underlying mechanism is mainly associated with the p53/SLC7A11/GPX4 signaling pathway.
Ferroptosis/drug effects* ; Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism* ; Breast Neoplasms/drug therapy* ; Signal Transduction/drug effects* ; Female ; Cell Line, Tumor ; Tumor Suppressor Protein p53/metabolism* ; Amino Acid Transport System y+/metabolism* ; Humans ; Reactive Oxygen Species/metabolism* ; Animals ; Mice ; Cell Proliferation/drug effects* ; Mitochondria/metabolism* ; Coenzyme A Ligases/metabolism* ; Cell Movement/drug effects* ; Benzopyrans

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*