Introduction: Medullary thyroid carcinoma (MTC) comprises sporadic and hereditary forms, the latter commonly associated with multiple endocrine neoplasia type 2 (MEN2) which is identifiable through genetic screening of germline RET protooncogene. We compared the clinicopathological features and outcomes of hereditary and sporadic MTC in our single centre. Methodology: We conducted a retrospective audit of patients with MTC from 2000 to 2026. Patients were classified as either hereditary or sporadic based on genetic testing and/or family history of MTC/MEN2A syndrome. Variables analyzed included age at diagnosis, mode of presentation, pre-operative calcitonin, tumor size, lymph node (LN) involvement, post-operative biochemical cure, repeat surgery and presence of structural residual/recurrent disease. Results: A total of 57 patients were included (18 hereditary [31.6%], 39 presumed sporadic [68.4%]) with a median follow-up of 7.5 years (IQR 1.5–12.4). Hereditary MTC was diagnosed at a significantly younger age than sporadic MTC (33.0 vs. 44.7 years, p = 0.010) where 33% of the cases were diagnosed via screening detection whereas sporadic MTC more commonly presented with symptomatic neck swelling (84.6% vs. 50.0%, p = 0.008). There were no significant differences in median pre-operative calcitonin (513.5 vs. 1148.0 pg/mL, p = 0.101), tumor size (24.5 vs. 22.5 mm, p = 0.301), or LN involvement (41.7% vs. 61.5%, p = 0.307) between hereditary and sporadic MTC. Long-term outcomes were also comparable, with no differences in biochemical status, need for repeat surgery or residual/recurrent structural disease. Conclusion Hereditary MTC presents earlier and is more frequently detected due to screening, whereas sporadic MTC often presents symptomatically. Long-term outcomes are not primarily determined by hereditary status alone. Early access to RET mutation testing with a view to initiating prophylactic treatments rather than post detection surgery may improve disease burden.
Thyroid Neoplasms ; Cohort Studies

Introduction: Hyponatremia is the most common electrolyte imbalance in hospitalized patients, associated with increased morbidity and mortality. Tolvaptan effectively raises serum sodium in SIADH. However, concerns regarding rapid overcorrection and safety persist. This study evaluates the efficacy, safety, and real-world usage patterns of tolvaptan in a tertiary care setting. Methodology: A retrospective single-centre observational study was conducted at Hospital Putrajaya using the electronic records of patients treated with tolvaptan from January 2020 to December 2025. Overcorrection was defined as >10 mmol/L increase within 24 hours, and non-response as <4 mmol/L increment at 24 hours. Results: Twenty-one patients were included, with a mean age of 66.7 years; 57% were male. Most (90.5%) received 7.5 mg initially. Mean baseline sodium was 118.1 ± 4.1 mmol/L. Tolvaptan produced rapid correction, with mean sodium increasing to 127.0 mmol/L at 24 hours (mean increment 8.9 mmol/L). Only one patient (4.8%) was a non-responder at 24 hours. Median time to sodium >130 mmol/L was 1 day, with 60% achieving this within 24 hours. At discharge, mean sodium was 130.4 mmol/L. Median length of stay following initiation was 5.5 days. Overcorrection occurred in 23.8% (n = 5), all in the 7.5 mg group, particularly among those with baseline sodium 115–120 mmol/L. No cases of osmotic demyelination syndrome (ODS) were observed. The mean internal for initiation is approximately 6 days from diagnosis. Tolvaptan usage increased and peaked in the first 3 years, but subsequently dropped and plateaued over the last 2 years. Conclusion Tolvaptan is safe and effective for sodium correction; although overcorrection remains a risk, no long-term sequelae of ODS were observed, underscoring the need for vigilant monitoring. Its use in Hospital Putrajaya remains limited, with delayed initiation possibly due to tolvaptan being considered a secondary treatment after failure of other options
Hyponatremia ; Tolvaptan

Introduction: Pheochromocytoma is a catecholamine-secreting adrenal tumor associated with major perioperative hemodynamic instability. When concurrent major pelvic pathology requires surgery, operative planning becomes particularly challenging. We describe the successful single-stage management of pheochromocytoma and a giant uterine fibroid, highlighting the importance of multidisciplinary coordination and perioperative optimization. Case: A 49-year-old female with symptomatic uterine fibroid was found to have proliferative endometrium on a pipelle biopsy. Computed tomography (CT) abdomen incidentally detected a right adrenal mass alongside a large posterior uterine fibroid (11.9 × 17.4 × 14.6 cm). CT adrenal protocol demonstrated a heterogeneously enhancing right adrenal mass (6.9 × 6.9 × 9.6 cm) with high unenhanced attenuation. Biochemical evaluation revealed markedly elevated 24-hour urinary metanephrine (4.7× upper limit) and normetanephrine (2.4× upper limit). Following multidisciplinary discussions, a single-stage surgical approach was planned after careful assessment of feasibility and perioperative risk in view of the uncertain malignant potential of the pelvic mass and to minimize repeated exposure to anesthesia. Preoperative optimization included transitioning from terazosin to phenoxybenzamine, with subsequent addition of bisoprolol for hemodynamic control. The operative strategy prioritized pheochromocytoma resection first, given its potential for significant hemodynamic instability. Progression to hysterectomy was contingent upon achieving adequate intraoperative hemodynamic stability following adrenalectomy, with continuous reassessment by the anesthetic and surgical teams. Right adrenalectomy was performed first, followed by total abdominal hysterectomy with bilateral salpingooophorectomy. Significant hemodynamic lability occurred during tumor manipulation, with hypertensive surges managed using sodium nitroprusside and remifentanil infusions. Following adrenal vein ligation and tumor removal, hypotension was managed with noradrenaline and additional adrenaline support as required. Total operative time was approximately 6 hours. Postoperatively, transient noradrenaline support was required but was rapidly weaned as hemodynamic stability was achieved. Conclusion Single-stage adrenalectomy and major pelvic surgery can be safely performed in selected patients with pheochromocytoma when guided by meticulous preoperative optimization, clear intraoperative sequencing, and close multidisciplinary coordination.
Pheochromocytoma ; Adrenalectomy ; Leiomyoma ; Hysterectomy

Introduction: Pheochromocytomas and paragangliomas (PPGL) are rare neuroendocrine tumors with high heritability. While most are benign, approximately 25% are malignant, defined by distant metastases. Molecular classification has identified three clusters, with Cluster 3 (Wnt-signaling) being exclusively somatic and associated with aggressive behavior. We report a rare case of metastatic malignant pheochromocytoma driven by a somatic DNMT3A mutation, highlighting its unique imaging characteristics and rapid clinical progression. Case: A 55-year-old female presented with paroxysmal hypertension, headache, and a 10-kg weight loss. Biochemical workup revealed markedly elevated 24-hour urine metanephrines (163 × ULN) and normetanephrines (47 × ULN). Imaging confirmed a 15-cm left adrenal mass with liver and widespread skeletal metastases. Functional imaging demonstrated a striking mixed avidity: liver metastases were predominantly fluorodeoxyglucoseavid (SUVmax 7.0), skeletal lesions showed high Ga-68 DOTATATE avidity (SUVmax 6.9), and the primary tumor exhibited the strongest avidity on 131 I-MIBG scan. Whole Exome Sequencing identified a rare pathogenic somatic variant in the DNMT3A gene (c.2645G>A) with no other germline or somatic mutations in known susceptibility genes. Despite adequate alpha-blockade and supportive care, the patient developed acute liver failure and coagulopathy, rendering her unfit for any form of invasive intervention and finally succumbing to the disease within 3 months of presentation. Conclusion This case underscores the aggressive nature of Cluster 3 PPGLs associated with DNMT3A mutations, which likely promote tumorigenesis via Wnt-pathway activation and epigenetic dysregulation. The discordant functional imaging reflects significant tumor heterogeneity, which may complicate diagnostic and therapeutic strategies. Given the rarity of DNMT3A-mutated PPGL (<1% of cases), this case report emphasizes the necessity of comprehensive molecular profiling in advanced disease to refine risk stratification and guide the development of precisionbased palliative management in rapidly progressive cases.

Introduction: Sodium-glucose-linked-transporter inhibitors (SGLT2-i) have demonstrated cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM), but patients aged ≥75 years remain underrepresented in major trials, creating uncertainty regarding their risk–benefit profile. Real-world data show mixed safety signals. In Malaysia, local evidence is limited despite a growing elderly diabetic population. This study evaluates the glycemic efficacy and safety of SGLT2-i in advanced elderly patients in a real-world public hospital setting. Methodology: We conducted a retrospective observational cohort study of patients aged ≥75 years with T2DM initiated on SGLT2-i in Hospital Putrajaya (2020–2024). Electronic records were reviewed for demographics, comorbidities, medications, and biochemical parameters. Outcomes at 6–12 months assessed glycemic control and safety. Adverse events and discontinuation rates were recorded. Patients with incomplete data, type 1 diabetes, active malignancy, or severe renal impairment were excluded. Results: A total of 104 patients (mean age 78.2 years; 54% female) were included with a high proportion (76.9%) classified as at high cardiovascular risk due to established macrovascular disease (57.7%) or nephropathy (53.8%). Indications for SGLT2-i initiation were glycemic control alone (69.2%) and together with cardiorenal protection (58.7%). Glycemic control remained stable (hemoglobin A1c: 7.66–7.45%; p = 0.076), with preserved renal function (estimated glomerular filtration rate: 58.65–58.11 mL/min/1.73 m²; p = 0.575). Overall safety was favorable, with 90.4% experiencing no adverse events. Minor adverse events included urinary tract infections (2.9%) and polyuria (1.9%). ASCVD-related hospitalizations occurred in 4.8% of patients, with a low discontinuation rate (7.7%). A statistically significant weight reduction was observed (baseline 66.67 kg, −1.01 kg; p = 0.005) but was not clinically significant. Proteinuria improvement was noted in 15.7% of patients. Conclusion SGLT2-i are safe and well-tolerated in elderly T2DM patients (≥75 years), with stable glycemic control, preserved renal function, and minimal adverse events, supporting their use in very elderly Asian populations.
Aged ; Diabetes Mellitus, Type 2 ; Sodium-Glucose Transporter 2 Inhibitors

Introduction: Subcutaneous once-weekly semaglutide (Sema-OW) (0.5, 1.0 mg) has been available in Malaysia since 2020, but is currently not listed in the MOH Medicines Formulary. MOH clinicians prescribe Sema-OW for limited patient numbers, on a “named patient basis” following a closely regulated application process, permitting use once multilevel approval is obtained. Our study aims to report on the glycemic and weight-lowering outcomes of SemaOW in a real-world MOH clinical setting. Methodology: A retrospective, single-arm, observational study was conducted in Hospital Putrajaya and Hospital Kuala Lumpur. The study population comprised adults with type 2 diabetes mellitus (T2DM) treated with Sema-OW for at least 6 months with hemoglobin A1c (HbA1c) and weight parameters available in their medical records. The primary endpoint was HbA1c change at 6 months. The secondary endpoints were the changes in HbA1c and weight from baseline to 12 months, proportion of patients achieving HbA1c <7%, and different levels of HbA1c reduction in 6 and 12 months (<0.5, 0.5–<1.0, 1–<2, ≥2%). Changes in concomitant glucose-lowering medications were additionally observed. Results: The cohort comprised 45 patients, with a mean age and disease duration of 53.3 and 16.3 years, respectively. Baseline mean weight was 100.3 kg, and body mass index (BMI) was 36.8 kg/m², with 88% in the obese BMI category. Baseline HbA1c was 7.9%, and HbA1c reduction was 0.74% at 6 months and 0.84% at 12 months. The proportions of patients achieving HbA1c reduction of <0.5, 0.5–<1.0, 1.0– <2.0, and ≥2.0% were 8.9, 26.7, 26.7, and 8.9%, respectively. The mean weight reduction from baseline was 4.93 kg at 6 months and 6.73 kg at 12 months. Concomitant insulin therapy was observed in 44%, with 31% reduction in total daily insulin requirement at the end of the study, along with simplification of insulin regimens. Conclusion Combination therapy with Sema-OW improved glycemic control with weight loss and enabled treatment deintensification in people with T2DM in Malaysian public tertiary diabetes care.
semaglutide ; Hospitals, Public ; Diabetes Mellitus

Introduction: The rising incidence of diabetic ketoacidosis (DKA) in type 2 diabetes mellitus (T2DM) represents a paradigm shift from its traditional recognition as a hallmark complication of type 1 diabetes mellitus (T1DM). However, contemporary data comparing clinical presentation, precipitating factors, and outcomes between these two populations remain limited. Methodology: In this retrospective observational study, all adult DKA admissions with T1DM or T2DM at a tertiary centre between 2001 and 2025 were studied. DKA was defined according to standard biochemical criteria. Electronic medical records were reviewed to extract demographic data, biochemical parameters, precipitating factors, management details, and clinical outcomes of all adult DKA admission in T1DM and T2DM. Patients aged <18 years or those with incomplete data were excluded. Results: A total of 601 DKA episodes were analyzed, comprising 130 (21.6%) in patients with T1DM and 471 (78.4%) in those with T2DM. Mean age was 26.9 ± 0.71 years for T1DM and 52.1 ± 0.7 years for T2DM. Gender distribution was balanced (male 48.3%, female 51.7%). Mean hemoglobin A1c (HbA1c) was 11.3 ± 0.3% in T1DM and 12.1 ± 0.2% in T2DM. Infection was the most common precipitating factor overall (69.0%), occurring more frequently in T2DM than in T1DM (74.7% vs. 56.2%), followed by medication non-adherence (62.4% vs. 43.8%). Significant differences were observed between groups in admission pH, bicarbonate (both p <0.001), blood ketones (p = 0.028), and HbA1c (p = 0.010), whereas anion gap (p = 0.056) and blood glucose levels (p = 0.755) did not differ significantly. Clinical outcomes were comparable with respect to intensive care unit (ICU) admission rates (40.0% in T1DM vs. 39.0% in T2DM, p = 0.779) and median resolution time (p = 0.462). However, the median length of hospital stay was significantly longer in T2DM (8.2 ± 0.32 vs. 5.4 ± 0.4 days; p <0.001). Overall mortality was 6.0%, with substantially higher mortality in T2DM compared to T1DM (7.4% vs. 0.8%, p = 0.013). Conclusion In this large regional series of adult DKA, most episodes occurred in T2DM. Despite similar ICU admission rates and time to resolution, T2DM was associated with more frequent infection-related precipitants, longer hospital stays, and higher mortality, underscoring the need for targeted preventive strategies in this population.
Adult ; Diabetes Mellitus, Type 1 ; Diabetic Ketoacidosis ; Diabetes Mellitus, Type 2

Introduction: The 2021 IDF-DAR risk calculator had been previously evaluated in multiple studies and subsequently widely accepted and applied in clinical practice as a practical standardized tool for patient risk stratification. Recently updated, the 2026 IDF-DAR Risk calculator enables a more individualized, evidence-related evaluation of patientrelated and disease-related risk factors, incorporating modern diabetes technologies, including continuous glucose monitoring (CGM), automated insulin delivery (AID) systems, and advanced insulin formulations to enhance risk stratification. This tool allows medical professionals to tailor Ramadan practices based on overall factors toward promoting safe fasting. Methodology: This prospective multicentre observational study recruited adults with Type 1 and Type 2 diabetes attending public hospitals nationwide. People with diabetes (PwD) intending to perform Ramadan fasting were invited to participate and assessed using the 2026 IDF-DAR Risk Calculator in the 6-week pre-Ramadan period between 30th January and 19th March 2026. Results: A total of 458 PwD were evaluated and stratified into low (15.7%), moderate (41%), and high risk (43.3%) categories. Most participants had Type 2 diabetes (83.6%), with 60.3% having a disease duration exceeding 10 years and 43% exhibiting poor glycemic control (hemoglobin A1c >9%). Insulin therapy was used by 76.4% of participants, including two individuals with Type 1 diabetes using AID systems. Most participants reported no recent hypoglycemia (76.4%), 81.0% performed glucose monitoring, and 3.3% used CGM. Severe comorbidities were uncommon, with 1.1% having unstable macrovascular disease and 4.4% advanced chronic kidney disease (estimated glomerular filtration rate <30). Notably, 72.2% received structured Ramadan education. Conclusion Majority of PwD attending tertiary diabetes clinics were in the moderate- to high-risk category and intended to fast despite medical advice against fasting in some cases. Although most participants were on insulin therapy, hypoglycemia was low in the pre-Ramadan period. Integration of modern technologies, advanced insulin therapies, and structured education may support safer fasting practices.
Risk Assessment ; Diabetes Mellitus ; Hospitals ; Fasting

Introduction: Bullous pemphigoid (BP) is the most common autoimmune blistering disease. Drug-induced BP has been increasingly reported, with dipeptidyl peptidase-4 (DPP-4) inhibitors, particularly vildagliptin, emerging as a notable cause. The pathogenesis is thought to involve the disruption of immune tolerance and epitope spreading, leading to a broader autoimmune response against basement membrane antigens beyond the classic NC16A domain of BP180. This case series highlights the variable clinical spectrum and therapeutic challenges in vildagliptin-induced BP. Case: A 74-year-old male with type 2 diabetes mellitus (T2DM), hypertension, dyslipidemia, and a history of stroke presented with a 2-month history of recurrent, pruritic, tense bullae. He had been on vildagliptin for 36 months. Histopathology confirmed subepidermal blistering, and direct immunofluorescence demonstrated linear IgG/C3 deposition at the dermo-epidermal junction, with positive anti-BP180 antibodies, diagnosing BP. Discontinuation of vildagliptin and initiation of systemic corticosteroids resulted in significant clinical improvement, allowing a rapid prednisolone taper to 5 mg daily without new bullae formation. A 62-year-old female with T2DM and dyslipidemia presented with bullous eruptions 3 months after initiating vildagliptin. Skin biopsy confirmed BP, revealing subepidermal blistering with eosinophils and linear C3/IgG deposition at the basement membrane zone. Vildagliptin was discontinued. Despite initial management with systemic corticosteroids, the disease course was refractory. The patient experienced a flare upon steroid taper and had persistent blistering on prednisolone 20 mg daily, necessitating the addition of azathioprine as a steroidsparing agent. Conclusion This case series illustrates the variable clinical course of vildagliptin-induced BP in which the therapeutic trajectories diverged significantly. Recognition of BP as a potential adverse effect of DPP-4 inhibitors is critical, and management should be individualized.

Introduction: Medullary thyroid carcinoma (MTC) has the highest familial predisposition syndrome of any hereditary cancer syndrome. The most common subtype of hereditary MTC is multiple endocrine neoplasia type 2A (MEN2A), which is an autosomal dominant syndrome characterized by MTC, pheochromocytoma, and primary hyperparathyroidism (HPP). This study evaluates the genotypic distribution, phenotypic manifestations, and clinical characteristics of MEN2A within a retrospective MTC cohort. Methodology: A retrospective audit of MTC patients was conducted at a tertiary centre. Patients with clinically or genetically confirmed hereditary MTC were identified for further analysis. Electronic medical records were reviewed for demographic data, RET germline mutations, occurrence of pheochromocytoma and HPP, laterality of disease, and documented surgical interventions. Results: In all, 18 patients (31.6%) were classified as hereditary from a cohort of 57 patients with a median age at diagnosis of 29.2 years. Among genetically confirmed cases with available variant data (n = 11), mutations predominantly involved exon 11 codon 634 (90.9%, n = 10), including p.Cys634Arg (n = 4), p.Cys634Tyr, and p.Cys634Ser, with one codon 618 mutation. Extrathyroidal manifestations were common. Pheochromocytoma occurred in 50.0% (n = 9), of which 77.8% (n = 7) were bilateral. Most patients underwent adrenalectomy, including bilateral procedures in those with bilateral disease. HPP was identified in 44.4% (n = 8), managed with selective parathyroidectomy. Both pheochromocytoma and HPP were present in 22.2% (n = 4), while isolated MTC occurred in 27.8% (n = 5). Conclusion Hereditary MTC in our cohort is predominantly associated with high-risk codon 634 RET mutations and demonstrates substantial penetrance of pheochromocytoma and HPP. The high frequency of bilateral adrenal involvement highlights the importance of systematic biochemical surveillance and appropriately timed surgical management in MEN2A. A nationwide registry would be timely.
Humans ; Multiple Endocrine Neoplasia Type 2a ; Thyroid Neoplasms