Introduction: Endothelial dysfunction (ED) is an early marker of atherosclerosis and plays a role in the pathophysiology of cardiovascular complications in type 2 diabetes mellitus (T2DM). Metabolic factors such as adiposity and insulin resistance contribute to early vascular dysfunction, particularly in patients with preserved kidney function. This study aimed to identify factors associated with ED in T2DM and early-stage chronic kidney disease (CKD) Methodology: This study was conducted at Universiti Teknologi MARA (UiTM), Sungai Buloh, and involved 107 adults with T2DM and estimated glomerular filtration rate ≥60 mL/min/1.73 m² (CKD stages 1–2). Endothelial function was assessed using ultrasound-based brachial artery flow-mediated dilation (FMD), with ≤7.1% defining ED. Clinical, anthropometric, metabolic, and renal parameters were compared between groups. Logistic regression analyses were performed to identify independent predictors, with p-values <0.05 considered statistically significant. Results: Of the cohort, 48.6% (n = 52) had abnormal FMD. They tended to have higher BMI (31.36 vs 28.38 kg/m², p = 0.020), larger waist circumference (100.48 vs 94.53 cm, p = 0.026), and were more likely to be on insulin therapy (71.2 vs 49.1%, p = 0.020). The total daily insulin dose was higher in the abnormal FMD group (0.48 vs 0.35 U/kg), but this difference did not reach statistical significance (p = 0.140). There were no significant differences in hemoglobin A1c, blood pressure, or renal parameters. In multivariate analysis, BMI (adjusted OR 1.07, 95% CI 1.00–1.14, p = 0.037) and insulin therapy (adjusted OR 2.43, 95% CI 1.07–5.51, p = 0.034) remained independently associated. Conclusion In patients with T2DM and early CKD, higher BMI and insulin therapy are independently associated with ED. These findings highlight the role of obesity and insulin resistance in early vascular dysfunction, emphasizing the importance of weighttargeted strategies alongside glycemic control and further identifying high-risk individuals to reduce cardiovascular risk.
Diabetes Mellitus, Type 2 ;

Introduction: Disseminated histoplasmosis is a rare but important cause of adrenal insufficiency (AI), particularly in tuberculosis (TB)-endemic regions, where it may mimic granulomatous diseases. Adrenal involvement occurs in up to 80% of disseminated cases, although overt AI is less common. Reported cases described bilateral adrenal masses mimicking malignancy or TB, even in immunocompetent individuals. Addisonian crisis may be the initial manifestation, especially when the diagnosis is delayed. In TB-endemic settings, fungal infections are often overlooked, leading to delayed diagnosis and inappropriate therapy. Case: We reported a case of a 68-year-old male with underlying diabetes mellitus who presented with fever, cough, dysphagia, and weight loss for 1 month. He was empirically treated as smear-negative disseminated TB. On day 2 of therapy, he developed hypotension (80/50 mmHg), hypoglycemia (3.9 mmol/L), hyponatremia (Na 129 mmol/L), and hyperkalemia (K 5.1 mmol/L), suggestive of adrenal crisis, and was started on intravenous hydrocortisone. Serum cortisol prior to treatment was 61 nmol/L. Computed tomography (CT) imaging revealed bilateral lipid-poor adrenal lesions (right: 3.6 × 2.2 × 4.9 cm, Hounsfield Unit (HU) 36 and absolute washout 33%; left: 3.5 × 2.4 × 5.4 cm; HU 35 and absolute washout 17%), raising suspicion of infectious or malignant etiologies. Endoscopic ultrasound-guided biopsy demonstrated necrotizing granulomatous inflammation with budding fungal yeasts on Pituitary Apoplexy Score and GMS staining, consistent with Histoplasma capsulatum. TB and malignancy were excluded. He received amphotericin B for 14 days, followed by oral itraconazole for 1 year, and oral hydrocortisone replacement. At 1-year follow-up, adrenal lesions remained stable on CT images, and he continued to require hydrocortisone replacement. Conclusion This case highlights the importance of considering disseminated histoplasmosis as a differential diagnosis of bilateral adrenal masses with AI, especially with poor response to anti-TB therapy. Early tissue diagnosis is essential, as imaging findings are non-specific. Prompt recognition is critical to prevent life-threatening adrenal crisis and improve clinical outcomes.
Histoplasmosis ; Tuberculosis

Introduction: Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM), with nerve conduction studies recognized as the diagnostic gold standard. Serum neuron-specific enolase (NSE) has been linked with DPN. This study aims to determine the prevalence of DPN among T2DM patients, evaluate clinical characteristics, and explore the relationship between NSE and DPN. Methodology: A cross-sectional study was conducted at Universiti Teknologi MARA Specialist Centre Sungai Buloh and Hospital Al-Sultan Abdullah, involving patients aged 18–60 years, diagnosed with T2DM for more than 5 years (n = 132). All participants underwent anthropometric measurement, completed the Michigan Neuropathy Screening Instrument evaluation, and biochemical parameters, including lipid profile, hemoglobin A1c, and serum creatine and NSE. The diagnosis of DPN was made based on positive NCS findings. Logistic regression was used to identify factors associated with DPN. Results: The study population had a mean age of 60.16 ± 10.28 years and a mean duration of diabetes of 14.82 ± 6.66 years. The prevalence of DPN was 51.5% (n = 68). Serum NSE levels were significantly higher (p = 0.003) and independently associated with the presence of DPN (adjusted odds ratio [OR] 1.033, 95% confidence interval [CI] 1.009–1.058, p = 0.006). Participants with DPN were also more likely to be on insulin therapy (p = 0.040). In addition, retinopathy (adjusted OR 3.567, 95% CI 1.528–8.329, p = 0.013) and elevated Urine Albumin-to-Creatinine Ratio levels indicating albuminuria (adjusted OR 1.031, 95% CI 1.002– 1.061, p = 0.037) were significantly associated with DPN. Conclusion More than half of the study population had DPN, which was significantly associated with both retinopathy and nephropathy, as well as with elevated serum NSE. This emphasizes the importance of early screening and highlights the role of NSE as a surrogate marker for neuropathy in diabetes.
Humans ; Diabetes Mellitus, Type 2 ; Diabetic Neuropathies ; Prevalence ; Phosphopyruvate Hydratase

Introduction: Type 2 diabetes mellitus (T2DM) and thyroid disorders are common endocrine conditions with a bidirectional relationship affecting glucose and lipid metabolism. Adiposity, particularly fat mass index (FMI), may influence thyroid function. but its association with thyroid dysfunction and glycemic control remains unclear, especially in Malaysia. This study aimed to determine the prevalence of thyroid dysfunction in T2DM and its association with glycemic control and FMI at Universiti Teknologi MARA (UiTM). Methodology: A cross-sectional study was conducted among patients with T2DM attending the Endocrine Clinic, UiTM, from December 2025 to March 2026. A total of 91 participants aged 18–70 years were recruited using convenience sampling. Demographic, clinical, anthropometric, and laboratory data were collected. Thyroid dysfunction was defined as thyroid-stimulating hormone (TSH) <0.38 or >5.33 mIU/L. Body composition was assessed using the InBody 380 to determine FMI. Data were analyzed using SPSS version 30 with descriptive statistics and Pearson correlation. Results: The prevalence of thyroid dysfunction among patients with T2DM was 7.7% (7/91), predominantly with low TSH levels. Mean hemoglobin A1c (HbA1c) in the overall study population was 7.59 ± 1.49%, and mean TSH was 1.42 ± 0.95 mIU/L, within the euthyroid range. Mean FMI was 11.95 ± 5.23 kg/m², exceeding normal ranges for both men (3–6 kg/m²) and women (5–9 kg/m²). FMI showed a positive correlation with TSH level (r = 0.379, p <0.001), indicating that higher adiposity was associated with higher TSH levels despite remaining within the euthyroid range. Pearson correlation showed a weak, non-significant negative correlation between HbA1c and TSH (r = −0.127, p = 0.229). Conclusion The prevalence of thyroid dysfunction among patients with T2DM in our cohort was relatively low at 7.7%. However, the significant correlation between FMI and TSH level, even within the euthyroid range, suggests that adiposity may exert a clinically relevant influence on thyroid function.
Diabetes Mellitus, Type 2 ; Prevalence ; Thyroid Gland ; Adipose Tissue

Introduction: Clinically important drug–drug interactions are a frequently overlooked cause of severe hypoglycemia in patients with type 2 diabetes mellitus (T2DM). Gliclazide is primarily metabolized via cytochrome P450 2C9 (CYP2C9), while fluconazole is a potent inhibitor of this enzyme.1,2 Concomitant administrations markedly increase gliclazide plasma concentration and prolong its hypoglycemic effect, substantially increasing the risk of severe and prolonged hypoglycemia. In some cases of refractory sulfonylureainduced hypoglycemia, octreotide may need to be considered early. Case: A 63-year-old Malay female with a 15-year history of T2DM on maximum-dose gliclazide (320 mg/day) presented with syncope and recurrent severe hypoglycemia 5 days after receiving a single oral dose of fluconazole 150 mg for a superficial fungal skin infection. Her other antidiabetic medications included metformin 1 g twice daily and vildagliptin 50 mg once daily. Her blood pressure on presentation was 151/74 mmHg, and her glucose level was 2.8 mmol/L. Her presentation was compounded by community-acquired pneumonia and acute kidney injury (estimated glomerular filtration rate 52 mL/min/1.73 m²). Biochemical evaluation excluded adrenal insufficiency, with normal serum cortisol (1,098 µg/dL), serum sodium (141 mmol/L), and serum potassium (4.6 mmol/L). Thyroid and liver function tests were normal. Despite repeated boluses of 50% dextrose and continuous infusion of 20% dextrose, recurrent hypoglycemia persisted for up to 48 hours after discontinuation of gliclazide, with glucose ranging from 1.7 to 5.1 mmol/L, reflecting prolonged sulfonylurea activity. Conclusion This case highlights a clinically significant yet preventable interaction between fluconazole and gliclazide, mediated through CYP2C9 inhibition, resulting in sustained hyperinsulinemic hypoglycemia. Gliclazide should be reduced or withheld prior to initiating fluconazole, and medication review should be performed at every consultation.
Fluconazole ; Gliclazide ; Hypoglycemia

Introduction: Hypocalcemia in patients with advanced malignancy is usually attributed to bone metastases, vitamin D deficiency, renal impairment, or antiresorptive therapy. Paclitaxel, a taxane-based chemotherapy agent widely used for breast cancer, is not commonly associated with calcium disturbances. Proposed mechanism includes renal tubular dysfunction, renal salt wasting, and disruptions in bone metabolism. In patients with underlying disorders of calcium homeostasis such as hypoparathyroidism, taxanebased chemotherapy such as Docetaxel and Paclitaxel may exacerbate calcium imbalance. We reported a case of recurrent hypocalcemia associated with paclitaxel therapy in a patient with metastatic breast cancer. Case: A 42-year-old female with metastatic breast cancer, involving the liver and bones, had previously undergone neoadjuvant chemotherapy, mastectomy, and adjuvant radiotherapy. Following the disease progression, she was commenced on weekly intravenous paclitaxel at a 20% dose reduction due to prior complications and underlying metabolic risk. She had a history of post-thyroidectomy hypoparathyroidism and had previously been intolerant to docetaxel during the neoadjuvant chemotherapy, which was complicated by hypocalcemia, likely secondary to renal salt wasting. During paclitaxel treatment, she developed recurrent symptomatic hypocalcemia, requiring multiple hospital admissions and repeated intravenous calcium gluconate infusions despite ongoing oral calcium and calcitriol supplementation, which were temporarily increased during the chemotherapy. These episodes occurred intermittently in temporal association with paclitaxel administration, with other causes of hypocalcemia were considered less likely. Conclusion Hypocalcemia associated with paclitaxel is rarely described in literature. This case highlights the importance of monitoring calcium level in patients receiving paclitaxel, particularly in those with pre-existing hypoparathyroidism.
Hypocalcemia ; Hypoparathyroidism ; Breast Diseases ; Paclitaxel

Introduction: Severe hypercalcemia is a life-threatening metabolic emergency that necessitates prompt initiation of systemic therapy due to the risk of cardiac arrhythmias. It is frequently linked to squamous cell carcinoma through the production of parathyroid hormone–related protein, which mediates the development of humoral hypercalcemia of malignancy. Case: This is a case of a 38-year-old male who was diagnosed 1 year ago with locally advanced poorly differentiated basaloid squamous cell carcinoma of the lower anterior mandibular alveolus involving cortical, medullary bone, and perineural invasion. He underwent extensive tumor resection with reconstruction, tracheostomy, and bilateral neck dissection, followed by multiple revision surgeries for postoperative complications. He completed adjuvant chemoradiotherapy. He presented with acute confusion without other systemic symptoms. His Glasgow Coma Scale was E4V4M5. Neurological and systemic examinations were unremarkable, and oral cavity assessment showed no evidence of recurrence. Investigations revealed severe hypercalcemia (5.94 mmol/L) with normal phosphate (1.16 mmol/L) associated with shortened QTc. Other tests were unremarkable, with no evidence of infection, uremia, liver dysfunction, or alternative metabolic causes. Lumbar puncture was unremarkable. His parathyroid hormone level was suppressed at 0.50 pg/ mL. Computed tomography brain showed no evidence of meningoencephalitis, hydrocephalus, cerebral oedema, or metastasis. Aggressive hydration was initiated alongside subcutaneous calcitonin, which was subsequently titrated. However, there was no clinical or biochemical improvement after 1 day, with persistent confusion and calcium remaining at 5.87 mmol/L. Subcutaneous denosumab was then administered, and hemodialysis was initiated on alternate days due to refractory hypercalcemia. This resulted in improvement of calcium levels to 3.2–3.6 mmol/L and resolution of confusion Conclusion Refractory hypercalcemia may represent a late manifestation of advanced squamous cell carcinoma and is an ominous prognostic indicator, necessitating prompt evaluation and oncologic management.
Calcitonin ; Denosumab ; Hypercalcemia ; Renal Dialysis ; Neoplasms

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome caused by mutations in the tumor suppressor gene MENIN, classically characterized by endocrine tumors of the parathyroid glands, pancreas, and pituitary. Beyond tumorigenesis, emerging evidence suggests a role for MENIN in immune regulation, with deficiency linked to CD4⁺ and CD8⁺ lymphocyte dysfunction and predisposition to autoimmunity. While autoimmune conditions such as thyroiditis and pernicious anemia have been described in MEN1, an association with autoimmune hemolytic anemia (AIHA) has not been previously reported. We describe a rare case of MEN1 associated with warm AIHA, highlighting a potential link between endocrine tumorigenesis and immune dysregulation. Case: A 56-year-old female presented with a 4-month history of lethargy, anorexia, weight loss, and painless jaundice. She is para 6 + 1, with no history of anemia in pregnancy, prior blood transfusions, or family history of hematological disorders. Examination revealed mild pallor, jaundice, and hepatomegaly without splenomegaly. She had a prior diagnosis of MEN1, with two hallmark features: primary hyperparathyroidism and a pancreatic neuroendocrine tumor. She underwent pancreatic enucleation, hemithyroidectomy, and hemiparathyroidectomy; histopathology demonstrated a benign thyroid nodule and parathyroid hyperplasia. Whole exome sequencing identified no pathogenic MEN1 mutation but revealed a c.1621A>G variant, classified as a non-deleterious polymorphism. Variants in TP53 and BRCA1 were also detected without phenotypic expression. Surveillance colonoscopy and mammography were unremarkable. Laboratory findings were consistent with warm AIHA, including elevated lactate dehydrogenase, indirect hyperbilirubinemia, low haptoglobin, reticulocytosis, and a positive direct Coombs test (immunoglobulin G). Peripheral blood film was nonspecific. She responded well to a tapering course of prednisolone. Conclusion This case highlights a possible association between MEN1 and autoimmune hemolysis. The presence of the MEN1 c.1621A>G variant, alongside TP53 and BRCA1 variants, raises the possibility of modifier effects influencing immune dysregulation. Further studies are needed to clarify this relationship.

Introduction: Hypothyroidism is the most common outcome following radioiodine (RAI) therapy for Graves’ disease, affecting up to 80% of patients, usually within 6 months. While symptoms are often nonspecific, musculoskeletal complaints may be the predominant or sole manifestation. Hypothyroid myopathy occurs in 30–80% of patients, typically causing myalgias, cramps, fatigue, and slowly progressive, symmetric proximal weakness with delayed reflex relaxation. We report an atypical case with subacute and evolving weakness after levothyroxine initiation. Case: A 43-year-old female with Graves’ disease underwent RAI therapy (25 mCi) and developed hypothyroidism 7 weeks later. She was started on levothyroxine 50 mcg daily. Two weeks into treatment, she presented with progressive proximal lower limb weakness (power 4/5), while distal strength and reflexes remained intact. Labs revealed elevated creatine kinase (259 U/L), hypokalemia (3.3 mmol/L), creatinine (57 µmol/L), and severe hypothyroidism (thyroid-stimulating hormone [TSH] 52.88 mIU/L, free thyroxine 4 [FT4] 7.79 pmol/L). Levothyroxine was increased to 100 mcg daily. Two weeks later, she developed proximal upper limb weakness (power 4/5), while lower limb strength had normalized. Nerve conduction studies and electromyography were unremarkable. Labs showed creatine kinase (244 U/L) and creatinine (58 µmol/L). As she remained hypothyroid (TSH 20.85 mIU/L, FT4 11.61 pmol/L), levothyroxine 100 mcg daily was continued. Her symptoms gradually improved alongside biochemical recovery (TSH 8.83 mIU/L, FT4 15.90 pmol/L) after 4 weeks, consistent with hypothyroid myopathy. Conclusion This case highlights an atypical subacute presentation of hypothyroid myopathy following RAI, with evolving weakness and transient worsening after starting thyroid hormone therapy. Although other serious causes should be excluded, clinicians must maintain a high index of suspicion to avoid unnecessary investigations and ensure timely optimization of thyroid hormone therapy, as clinical improvement parallels biochemical recovery.
Iodine Radioisotopes ; Muscular Diseases

Introduction: Thyroid storm is a life-threatening endocrine emergency with a mortality rate of 8–25% despite optimal therapy. Some patients exhibit a refractory phenotype characterized by rapid clinical deterioration and failure of conventional treatment, necessitating early escalation. Therapeutic plasmapheresis and lithium represent adjunctive therapies targeting different aspects of thyroid hormone physiology, yet their combined use remains underexplored. Case: A 55-year-old male with Graves’ disease, non-adherent to treatment since 2020, presented with fever, palpitations, and dyspnea for 2 days. He recently started on carbimazole 30 mg daily and propranolol 1 week prior. On examination, blood pressure was 158/74 mmHg, heart rate 180 bpm, Glasgow Coma Scale 15/15 with bibasal crepitations. Electrocardiogram showed atrial fibrillation at 168 bpm. His Burch-Wartofsky score was 95, consistent with thyroid storm. Standard therapy with propylthiouracil 250 mg QID, Lugol’s iodine, intravenous hydrocortisone 100 mg TDS, and carvedilol was commenced. However, after 3 days of treatment, he developed acute confusion and persistent fast atrial fibrillation requiring cardioversion. Liver function remained normal. Plasmapheresis was initiated on day 4 for six sessions. Propylthiouracil was switched to methimazole due to a declining white cell count from (5.5– 3.2 ×10⁹/L). Lithium 300 mg BD was added on day 13 due to inadequate free thyroxine 4 (FT4) reduction. After 1 week of combined therapy, FT4 decreased from 70 to 35 pmol/L. Conclusion Early recognition of refractory disease and timely escalation are critical as refractory thyroid storm carries high mortality, especially with cardiovascular and neurological involvement. When conventional therapy fails, plasmapheresis facilitates rapid clearance of circulating thyroid hormones and inflammatory mediators, while lithium inhibits thyroid hormone release, providing an alternative mechanism when thionamides alone are insufficient. Their combined use offers a synergistic approach and targets both circulating and intrathyroidal hormone pools, suggesting that early dual-modality intervention is essential to overcome therapeutic resistance and improve overall outcomes in refractory disease.
Lithium ; Thyroid Crisis ; Plasmapheresis