Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication associated with significant morbidity and healthcare burden. Despite advances in diabetes care, recurrent DKA remains common, often reflecting gaps in treatment adherence and patient education. Identifying predictors of recurrence is crucial for risk stratification and targeted intervention. Methodology: We conducted a retrospective observational study of all adult DKA admissions to a tertiary centre between 2001 and 2025. Electronic medical records were reviewed for demographic data, biochemical parameters, precipitating factors, and clinical outcomes. DKA was defined using standard biochemical criteria. Recurrent DKA was defined as ≥2 admissions during the study period. Factors associated with recurrent DKA admissions were analyzed. Patients under the age of 18 years and those with missing vital information were excluded. Results: A total of 667 DKA admissions, comprising 566 patients, were identified, of which 101 admissions (15.1%) were recurrent, involving 65 patients. Among recurrent DKA episodes, the most common precipitating factors were infection (64.4%) and insulin omission (62.4%). After multivariate analyses, patients with type 1 diabetes mellitus (T1DM) were more likely to develop recurrent DKA compared to those with type 2 diabetes mellitus (aOR 4.16; 95% confidence interval [CI] 2.58–6.70; p <0.001). Insulin omission was strongly associated with recurrent DKA (aOR 2.29; 95% CI 1.46–3.60; p <0.001). In contrast, baseline glycated hemoglobin and chronic kidney disease were not significantly associated with recurrence. Diabetic counseling during the first DKA admission did not reduce recurrent DKA. There were no significant differences in mortality (3.9% vs 6.2%, p = 0.524) or critical care admission rates (40.6% vs 38.7%, p = 0.718) between recurrent and first DKA episodes. Conclusion Recurrent DKA accounts for a substantial proportion of DKA admissions and is strongly associated with insulin omission and T1DM. Our findings suggest that recurrent DKA is driven predominantly by behavioral and adherencerelated factors, indicating the need for multidisciplinary interventions beyond standard inpatient counseling.
Diabetic Ketoacidosis ; Retrospective Studies

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: Diabetic ketoacidosis (DKA) in pregnancy is an uncommon yet life-threatening emergency, with disproportionate risks to both mother and fetus. Pregnancy-specific physiological changes predispose patients to rapid metabolic decompensation, often with atypical presentations. Despite this, local data remain limited. We describe the clinical profile, precipitating factors, and outcomes of DKA in pregnancy in a tertiary centre, with emphasis on potentially preventable triggers. Cases: Nine pregnant patients with DKA were identified from a retrospective review of all cases admitted for DKA from 2002 to 2025. Mean age was 31.67 ± 5.20 years; all were Malay. The majority had type 2 diabetes mellitus (55.6%), followed by type 1 diabetes (33.3%) and latent autoimmune diabetes in adults (11.1%). The mean period of amenorrhea was 19.67 ± 12.62 weeks. Infection was the leading precipitant (44.4%), with additional triggers including insulin omission (22.2%), hyperemesis gravidarum, preterm labor, steroid exposure, and perioperative fasting. Most diagnoses were made in the emergency department (55.6%). Biochemical parameters reflected significant severity (mean bicarbonate 7.89 ± 2.98 mmol/L; anion gap 25.00 ± 5.81), with 88.9% classified as severe DKA. Intensive Care Unit (ICU) care was required in 77.8% of cases. The majority (77.8%) were admitted to the ICU unit, with a median time to resolution of 13.00 ± 12.00 hours (interquartile range [IQR]), and the median hospital length of stay was 7.00 ± 5.00 days (IQR). Complications during treatment included hypokalemia (33.3%), acute kidney injury (22.2%), and hypoglycemia (11.1%). Rebound DKA occurred in one-third of patients. All patients were discharged clinically stable. Outcome data demonstrated pregnancy loss in three cases and one preterm birth. Conclusion DKA in pregnancy remains a severe and resource-intensive condition. This series highlights missed opportunities in prevention, with modifiable precipitants such as infection and insulin omission commonly identified. The high severity at presentation suggests delays in recognition. Early detection, optimized metabolic care, and targeted preventive strategies are crucial to improving maternal and fetal outcomes.
Female ; Pregnancy ; Diabetic Ketoacidosis

Introduction: Brown tumors are rare skeletal manifestations of primary hyperparathyroidism (PHPT), now seen in less than 5% of cases due to widely accessible biochemical screening. Despite being benign, they can mimic malignant bone lesions, making diagnosis challenging. Case: A 45-year-old female presented with lethargy and hypercalcemia (corrected calcium 3.5 mmol/L) and was discharged after intravenous zoledronate. She returned 1 week later with an enlarging gingival mass present for 2 months but not previously disclosed, with a strong family history of malignancy. Examination revealed a 6 × 3 cm pedunculated lesion over the right alveolar ridge. Biochemistry showed persistent hypercalcemia (2.7–2.9 mmol/L), hypophosphatemia, and elevated alkaline phosphatase. Contrast-enhanced computed tomography of the neck demonstrated lytic mandibular and skull changes, raising suspicion for malignancy. Tumor markers and multiple myeloma screening were negative. Parathyroid hormone (PTH) later returned markedly elevated at 222.1 pg/mL (upper limit of normal 56.9 pg/mL), consistent with PHPT, alongside concomitant vitamin D deficiency. Excision biopsy of the mandibular lesion confirmed a brown tumor on histopathology. Following preoperative localization, she underwent left parathyroidectomy and recovered without hungry bone syndrome. Histology confirmed a parathyroid adenoma, and she has remained normocalcemic since. Brown tumors arise from prolonged osteoclastic activity and represent advanced PHPT. Craniofacial involvement is rare, with the mandible affected in 4–5% of cases, and lesions may clinically and radiologically mimic primary bone tumors or metastases, creating diagnostic uncertainty. Hypercalcemia should be systematically investigated to determine the underlying cause, with early measurement of PTH to distinguish PTH-dependent from PTH-independent etiologies. Untreated brown tumors may result in bone pain, deformity, pathological fractures, and functional impairment, highlighting the importance of early detection and management. Conclusion Brown tumors, although rare, remain an important differential diagnosis for lytic bone lesions in the context of hypercalcemia. Early measurement of PTH and careful clinical examination are essential to avoid misdiagnosis and prevent disease-related morbidity.
Neoplasms

Introduction: Pituitary macroadenomas may present with mass effects, hypopituitarism, or hormone hypersecretion. Hyperprolactinemia, resulting from a prolactin-secreting tumor or stalk compression, typically suppresses gonadotropins. Thus, elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with low testosterone in this context are unusual. We report a macroprolactinoma with a clinically non-functioning gonadotroph adenoma. Case: A 69-year-old male presented with acute giddiness and headache while in Vietnam. He reported reduced libido but no visual symptoms or galactorrhea. Examination showed no neurological deficits, normal visual fields, and secondary sexual characteristics; bilateral testes volume of 25 mL. Magnetic resonance imaging (MRI) brain revealed a 1.6 × 2.2 × 2.1 cm pituitary macroadenoma compressing the optic chiasm and pituitary stalk. Initial pituitary evaluation demonstrated hyperprolactinemia (prolactin >200 µg/L; normal 2.4–13.1), central hypothyroidism (T4 6.8 pmol/L [7.8–14.4], thyroid-stimulating hormone 2.3 mIU/L [0.38–5.3]), elevated FSH (21.5 IU/L [1.2–19.2]) and LH (191 IU/L [1.24–8.62]), low testosterone (8.88 nmol/L), normal insulin-like growth factor 1 (IGF-1) (68 µg/L [46.5–191.9]), and cortisol 237 nmol/L. Cabergoline was initiated at 0.25 mg twice weekly and titrated to 1 mg twice weekly over 4 months, alongside levothyroxine 25 µg daily. Repeated MRI brain 2 months after cabergoline initiation showed a persistent macroadenoma (1.7 × 2.2 × 2.2 cm) with bilateral cavernous sinus extension. Prolactin decreased to <170 µg/L, central hypothyroidism persisted; levothyroxine was optimized, and hydrocortisone was initiated. At the 5-month follow-up, prolactin further improved to 57 µg/L. Central hypothyroidism and borderline adrenal function persisted, requiring continued replacement therapy. Testosterone remained low-normal (10.2 nmol/L) despite elevated FSH (15.4 IU/L) and LH (92 IU/L). Followup MRI and hormonal reassessment were planned in May 2026. Conclusion Profoundly elevated prolactin level >200 µg/L and response to cabergoline reflect true prolactinoma rather than stalk effect. Persistently low testosterone with discordant high FSH/LH suggests a non-functioning gonadotroph component producing biologically inactive gonadotropins. Definitive diagnosis requires histopathological confirmation, while serial biochemical and radiological follow-up guides management and clarifies tumor subtype.
Gonadotrophs ; Hyperprolactinemia

Background/Aims: Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM. Methods: Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis. Results: Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL. Conclusion This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM.

Background/Aims: This study aims to evaluate the effects of acute codeine administration on primary and secondary esophageal peristalsis in patients with ineffective esophageal motility (IEM). Methods: Eighteen IEM patients (8 women; mean age 37.8 years, range 23-64 years) were enrolled in the study. The patients underwent highresolution manometry exams, consisting of 10 single wet swallows, multiple rapid swallows, and ten 20 mL rapid air injections to trigger secondary peristalsis. All participants completed 2 separate sessions, including acute administration of codeine (60 mg) and placebo, in a randomized order. Results: Codeine significantly increased the distal contractile integral (566 ± 81 mmHg · s · cm vs 247 ± 36 mmHg · s · cm, P = 0.001) andshortened distal latency (5.7 ± 0.2 seconds vs 6.5 ± 0.1 seconds, P < 0.001) for primary peristalsis compared with these parameters after placebo treatment. The mean total break length decreased significantly after codeine treatment compared with the length after placebo (P= 0.003). Codeine significantly increased esophagogastric junction-contractile integral (P= 0.028) but did not change the 4-second integrated relaxation pressure (P= 0.794). Codeine significantly decreased the frequency of weak (P= 0.039) and failed contractions (P= 0.009), resulting in increased frequency of normal primary peristalsis (P < 0.136). No significant differences in the ratio of impaired multiple rapid swallows inhibition and parameters of secondary peristalsis were detected. Conclusions In IEM patients, acute administration of codeine increases contraction vigor and reduces distal latency of primary esophageal peristalsis, but has no effect on secondary peristalsis. Future studies are required to further elucidate clinical relevance of these findings, especially in the setting of gastroesophageal reflux disease with IEM.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp.and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Background/Aims: Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM. Methods: Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis. Results: Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL. Conclusion This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM.

Background/Aims: Activation of the cold receptor, transient receptor potential melastatin 8 (TRPM8) by menthol inhibits esophageal secondary peristalsis in healthy adults. Ineffective esophageal motility (IEM) is common. This study is to evaluate the effects of acute infusion of menthol on esophageal peristalsis in patients with IEM. Methods: Twenty patients with IEM (males 11, mean age 36) were studied for esophageal peristalsis using high-resolution manometry. All participant had primary peristalsis performed with 10 water swallows and secondary peristalsis generated with 10 rapid air injections of 20 mL via mid-esophageal infusion port. Two different sessions by randomly performing acute administration of placebo or menthol (3 mM) were used for testing their effects on esophageal peristalsis. Results: Menthol infusion had no effects on distal contractile integral (P = 0.471), distal latency (P = 0.58), or complete peristalsis (P = 0.251). Menthol infusion did not change basal lower esophageal sphincter pressure (P = 0.321), esophagogastric junction contractile integral (P = 0.758), or integrated relaxation pressure (P = 0.375) of primary peristalsis, but reduced upper esophageal sphincter pressure (P = 0.037). Infusion of menthol significantly reduced the frequency of secondary peristalsis for air injects of 20 mL (P = 0.002), but did not affect distal contractile integral of secondary peristalsis for air injections of 20 mL. Conclusion This work has suggested that activation of TRPM8 by menthol can attenuate mechanosensitivity of secondary peristalsis in response to rapid air distension regardless of the presence of IEM.