Introduction: Primary aldosteronism (PA), most commonly caused by aldosterone-producing adenomas (APAs), represents the leading form of surgically curable secondary hypertension. While genomic studies have elucidated the mutational landscape of APAs, the spatial organisation and functional role of immune populations across APAs, aldosterone-producing micronodules (APMs), and adjacent adrenal cortex remain poorly defined at single-cell resolution. Methodology: Single-cell RNA sequencing (scRNA-seq) was integrated with spatial transcriptomics in APAs and paired adjacent adrenal cortex, complemented by immunohistochemical (IHC) validation. Immune populations were spatially mapped using canonical markers (CD14, CD68, CD163, HLA-DR, CD8A, and CD4) across defined adrenocortical regions. Results: The adrenal microenvironment in PA demonstrates structured immune organisation rather than passive infiltration. CD14+ monocyte-lineage cells localize intraparenchymally within APAs (n = 10), intercalating between CYP11B2+ aldosterone-producing cells and forming a pattern distinct from perivascular immune niches. scRNA-seq further identified a transcriptionally distinct CD14+ population within the zona reticularis (zR) that co-expresses steroidogenic markers (CYB5A, SULT2A1, TSPAN12) while lacking canonical monocyte transcripts. IHC supported this observation, demonstrating CD14 expression within adrenocortical zR parenchymal cells (n = 5). In parallel, CD4 and HLA-DRA exhibited diffuse cytoplasmic staining within zR parenchymal cells in the absence of classical macrophage marker coexpression (CD68), suggesting non-canonical or context-dependent expression within steroidogenic compartments. CD68+ and CD163+ macrophages were sparsely distributed across APA, APM and adjacent cortex, consistent with lowdensity tissue-resident populations, while CD8A+ cytotoxic lymphocytes were enriched in APAs and APMs with diffuse parenchymal cytoplasmic staining of CD8A additionally observed within the zR. Conclusion These findings reveal a previously unrecognized spatially organised immune-steroidogenic interface within the adrenal cortex. The presence of immune-associated transcriptional and protein signatures within zR cells suggests potential functional plasticity of steroidogenic cells, possibly extending to antigen presentation-related pathways, warranting further mechanistic investigation
Hyperaldosteronism ; Humans

Introduction: Accurate preoperative localization is essential for the surgical management of primary hyperparathyroidism (PHPT). Although ultrasound, technetium-99m sestamibi scintigraphy, and 4D-CT provide high localization rates, a subset of patients have non-localizing or discordant imaging. Selective parathyroid venous sampling (PVS) is an invasive adjunct that measures regional parathyroid hormone (PTH) gradients to aid localization in challenging cases. We present a threepatient case series demonstrating the utility of PVS in diagnostically complex PHPT. Cases: We retrospectively reviewed three female patients (ages 44–63) with biochemically confirmed PHPT who underwent selective PVS following negative or discordant imaging. Venous sampling was performed via femoral access with catheterization of bilateral internal jugular, brachiocephalic, and bilateral thyroidal veins. PTH levels were measured at each site and compared to peripheral levels to identify regional gradients. Surgical findings, intraoperative parathyroid hormone monitoring (IOPTH), histopathology, and postoperative biochemical outcomes were recorded. All patients had non-localizing or discordant preoperative imaging (USG, sestamibi, 4D-CT). PVS identified significant PTH gradients, guiding focused parathyroidectomy. IOPTH monitoring confirmed successful excision in all operated patients. Histopathology confirmed parathyroid adenoma in two cases; in the third case, the parathyroid tissue was identified within the thyroid gland. Postoperative PTH levels suppressed (range 0.79–1.48 pg/mL) in keeping with successful parathyroidectomy. Conclusion PVS effectively lateralized disease in imaging-negative PHPT and directly guided surgical management. When conventional imaging fails, PVS combined with intraoperative PTH monitoring enables targeted surgery and favorable biochemical outcomes.
Humans

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: Diabetes mellitus (DM) is a significant comorbidity associated with adverse tuberculosis (TB) treatment outcomes and remains an ongoing clinical challenge. Chronic hyperglycemia impairs host immune responses, particularly macrophage function, leading to delayed bacillary clearance. This contributes to poorer outcomes, including delayed sputum conversion, prolonged treatment duration, relapse, and increased mortality. Poor glycemic control is a key modifiable factor influencing these outcomes. This study aimed to evaluate the impact of glycemic control at diagnosis on TB treatment outcomes in a Malaysian cohort. Methodology: A retrospective cross-sectional audit was conducted using the TB clinic registry at Hospital Sungai Buloh from 2022 to 2025. Adult patients (≥18 years) with confirmed TB (any form) and DM (Type 1 or Type 2) with complete records were included. Of 241 patients screened, 131 were included after exclusions due to incomplete records (29.9%), transfer (29.9%), loss to follow-up (19.9%), and drug-resistant TB (2.9%). Data collected included demographics, hemoglobin A1c (HbA1c) at diagnosis, sputum conversion duration, treatment duration, type of DM therapy, and clinical outcomes. Results: The cohort had a mean age of 53 years, with 97% having Type 2 DM. Mean HbA1c at diagnosis was 10.5%. Poorer glycemic control was associated with delayed sputum conversion. Patients who achieved sputum conversion by 8 weeks had an average HbA1c of 9.6%, compared to 11.8% in those with delayed conversion. Longer treatment duration was associated with higher HbA1c (mean 10.5, 8.6, and 11.8% for 6-, 12-, and 18-month regimens, respectively). Relapse analysis demonstrated a trend towards higher HbA1c with increasing relapse episodes (11.2, 13.75, and 14.5% for one, two, and three relapses, respectively). Overall mortality was 17% (22/131), with markedly higher mean HbA1c in deceased patients compared to survivors (16.0% vs 10.5%). Conclusion Poor glycemic control at TB diagnosis is associated with delayed sputum conversion, prolonged treatment duration, and increased mortality. These findings are consistent with regional evidence, including a South Asian systematic review (Gautam et al., 2021), demonstrating higher mortality and treatment failure in patients with TB and DM. Early and aggressive optimization of glycemic control, alongside standard anti-TB therapy, is essential to improve outcomes.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Treatment Outcome ; Tuberculosis

Introduction: Improving glycemic control while minimizing unnecessary insulin exposure is an important goal in diabetes management. The Rapid Optimization Clinic (ROC) was established as a structured multidisciplinary service to support therapy individualization, close follow-up, and timely insulin deintensification. This audit evaluated early changes in glycated hemoglobin A1c (HbA1c) and insulin treatment burden following ROC care over 3 months. Methodology: We conducted a retrospective audit of routine clinical data from patients with diabetes managed in the ROC at a district hospital. Baseline and 3-month HbA1c and insulin data were extracted from non-electronic clinic records. Insulin dose was standardized as total daily dose (TDD) in units/kg/day. Insulin deintensification was evaluated primarily by change in TDD from baseline to 3 months and by the proportion of patients who discontinued insulin during follow-up. Paired analyses were performed for patients with complete baseline and follow-up data for each outcome. Continuous variables are presented as mean ± standard deviation or median with interquartile range, as appropriate. Exploratory analyses were undertaken to assess whether available patient factors were associated with HbA1c improvement. Results: Twenty-three patients were included. Paired HbA1c data were available for 12 patients, whereas paired TDD data were available for 21 patients. Mean HbA1c decreased from 10.78 ± 2.59% at baseline to 8.42 ± 2.29% at 3 months, representing a mean reduction of 2.36 percentage points (95% confidence interval [CI] 0.09–4.62; p = 0.043). Mean TDD decreased from 0.434 ± 0.248 to 0.286 ± 0.313 units/kg/day, corresponding to a mean reduction of 0.148 units/kg/day (95% CI 0.077–0.219; p <0.001). Insulin was discontinued in 9 of 21 patients (42.9%). No clear association was observed between HbA1c improvement and age, sex, or number of visits. Interpretation is limited by the small sample size, reflecting the early phase of a newly established clinic. Conclusion In this early audit, ROC care was associated with clinically meaningful improvement in glycemic control and significant insulin deintensification over 3 months. These findings support the potential role of a structured multidisciplinary optimization clinic in delivering individualized diabetes care and facilitating safe reduction of insulin burden.
Humans ; Glycemic Control ; Retrospective Studies ; Diabetes Mellitus ; Insulins

Introduction: Diabetic retinopathy (DRP) is the most common microvascular complication of diabetes, affecting approximately 30% of patients with type 2 diabetes and over half of those with type 1 diabetes. It remains a leading cause of preventable blindness among adults worldwide. Early stages are frequently asymptomatic, making regular diabetic eye screening essential to detect sight-threatening changes before irreversible vision loss occurs. In Malaysia, where diabetes prevalence has reached 15.6% among adults (NHMS 2023), the effective implementation of annual retinal screening is crucial. Malaysian National Clinical Practice Guidelines recommend an annual retinal screening among type 2 diabetes mellitus (T2DM) patients. This clinical audit evaluated adherence to DRP screening. Methodology: A retrospective clinical audit was conducted at Pusat Perubatan Angkatan Tentera (PPAT), Kem Sungai Besi, to evaluate compliance with national DR screening standards among adults with T2DM. Thirty eligible patient records were reviewed. Three key indicators were assessed: (1) documentation of visual acuity at diagnosis, (2) annual fundoscopy, and (3) referral for fundus photography within the preceding 12 months. Performance was benchmarked against the 80% standard. Data were analyzed descriptively. Results: The median age group was 55–59 years, with equal gender distribution. Screening adherence was substantially below target: visual acuity assessment at diagnosis, 23.3%; annual fundoscopy, 26.7%; and fundus imaging referral, 36.7%. All screening indicators were below the recommended standard. Conclusion This audit reveals a significant implementation gap between national guidelines and routine practice. Structured workflow integration and documentation reinforcement strategies need to be emphasized. Additional measures include strengthening patient education and reinforcing guideline-based practice through regular CME sessions. However, a re-audit has not yet been conducted at the time of clinical audit reporting. An ongoing evaluation will be essential to determine the effectiveness and sustainability of these interventions in reducing preventable diabetic vision loss at PPAT Sungai Besi.
Humans ; iabetes Mellitus, Type 2 ; Diabetic Retinopathy ; Clinical Audit

Introduction: Cushing’s disease (CD) in adolescents may present with subtle clinical features, resulting in a significant diagnostic challenge. We report a case of a young lady whose CD initially masqueraded as Type 2 diabetes (T2D), highlighting the difficulties in differentiating early hypercortisolism from T2D. Case: A 12-year-old female was incidentally diagnosed with diabetes during routine medical screening. Examination revealed an overweight female without the classical features of Cushing’s syndrome. Due to the presence of acanthosis nigricans, a diagnosis of T2D was initially made. Her diabetes remained well-controlled with a single oral glucose-lowering drug. The diagnostic challenge became apparent over time. She experienced delayed menarche at the age of 17, and a diagnosis of Cushing’s syndrome was suspected when she subsequently developed hypertension and reduced bone mineral density. Biochemical evaluation was consistent with adrenocorticotropic hormone (ACTH)- dependent hypercortisolism, evidenced by the failure of serum cortisol suppression on low dose and overnight dexamethasone suppression tests. Her 24-hour urinary cortisol was elevated twofold, and plasma ACTH was elevated (17.8 pmol/L). MRI demonstrated a right-sided pituitary microadenoma (0.3 × 0.5 × 0.3 cm), and inferior petrosal sinus sampling confirmed the diagnosis of CD. She underwent endoscopic transsphenoidal surgery 7 years later, which was complicated by panhypopituitarism and cranial diabetes insipidus. Postoperatively, CD was cured, with the resolution of her metabolic comorbidities. Conclusion Despite the increasing prevalence of T2D in adolescents, clinicians must recognize the diagnostic challenge of CD in this age group. Atypical manifestations in a presumed T2D patient should prompt consideration of Cushing’s syndrome.
Adolescent ; Humans ; Diabetes Mellitus, Type 2

Introduction: Multiple autoimmune syndrome (MAS) type 3 is characterized by the coexistence of autoimmune thyroid disease with other organ-specific or systemic autoimmune disorders, excluding adrenal insufficiency. MAS represents a form of polyautoimmunity, in which shared immunological mechanisms contribute to clustering of multiple autoimmune diseases within a single individual. Recent studies suggest the clinical spectrum of MAS continues to expand, with increasing recognition of diverse autoimmune combinations across different organ systems. However, detailed clinical characterization of MAS type 3 involving overlapping endocrine and neuromuscular autoimmune diseases in young adults remains limited. Cases: We report four young adults (aged 21–37 years) with heterogeneous manifestations of MAS type 3 involving endocrine and systemic autoimmune diseases. Autoimmune thyroid disease was identified in three patients, all diagnosed with Graves’ disease with suppressed thyroidstimulating hormone, elevated free thyroxine, and positive thyrotropin receptor antibodies. Autoimmune diabetes was present in three patients, including latent autoimmune diabetes in adults (LADA) and type 1 diabetes mellitus, with variable glycemic control (hemoglobin A1c range 6.7–13.9%) and C-peptide levels ranging from preserved to markedly reduced. Myasthenia gravis was observed in three patients. Additional autoimmune conditions included systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, and ulcerative colitis. Notably, rare combinations such as Graves’ disease with LADA and myasthenia gravis, as well as coexistence with systemic autoimmune diseases, were identified. All patients received individualized multidisciplinary management. Clinical and biochemical improvement was observed in all cases, with stabilization of both endocrine and systemic autoimmune manifestations. Conclusion This case series highlights the heterogeneous and expanding clinical spectrum of MAS type 3, including rare combinations of autoimmune endocrine and systemic diseases in young adults. Early recognition of autoimmune clustering and comprehensive screening are essential to optimize management and improve outcomes. These findings provide insights into autoimmune disease clustering and support the need for proactive multidisciplinary management strategies.
Young Adult ; Humans ; Autoimmune Diseases

Achondroplasia (ACH) is a common inherited skeletal dysplasia (inherited dwarfism) that compromises quality of life across the lifespan. In 2021, vosoritide became the first approved precision therapy for ACH and is now available in more than 40 countries. Compared with prior symptomatic measures, vosoritide has demonstrated favorable efficacy and a reassuring safety profile. Nevertheless, existing international ACH guidelines largely emphasize complication management and symptomatic care, and there is no unified consensus on pharmacologic therapy. To address this gap, an international expert group developed the International Consensus Guidelines for the Implementation and Monitoring of Vosoritide Therapy in Patients with Achondroplasia providing systematic recommendations that span the continuum of care - from initial patient contact and pre-treatment assessment to medication counseling, injection training, and long-term outcome monitoring. These recommendations complement and refine current management and nursing protocols for individuals with ACH and offer practical guidance for clinicians across diverse regions. This article highlights key elements of the guideline to provide evidence-based support and clinical direction for healthcare professionals in China treating children with ACH using vosoritide.
Humans ; Achondroplasia/drug therapy* ; Consensus ; Practice Guidelines as Topic ; Child

OBJECTIVE: To explore the clinical phenotypes and genetic characteristics of five children with Lamb-Shaffer syndrome (LAMSHF). METHODS: Five children with LAMSHF diagnosed at the Department of Pediatrics, the First Medical Center of Chinese PLA General Hospital from April 2021 to December 2024 were selected as study subjects. Clinical data of the children was collected. Genomic DNA was extracted from peripheral blood samples of the children and their parents. Whole exome sequencing (WES) was carried out to screen for variants. This study was approved by the Medical Ethics Committee of the Chinese PLA General Hospital (Ethics No.: S2025-411-01). RESULTS: All five children had presented with global developmental delay. Among them, two had manifestations of autism spectrum disorder, two had abnormal electroencephalogram findings, four had abnormal MRI results, and two had ocular abnormalities. WES has detected five novel variants in the SOX5 gene. Among these, c.1771G>C (p.Gly591Arg) was unreported previously. Sanger sequencing confirmed that none of the parents had carried the same variants, suggesting that they were all de novo variants. According to the guidelines from the American College of Medical Genetics and Genomics (ACMG), two nonsense variants and one missense variant were classified as pathogenic, whilst two missense variants were classified as likely pathogenic. CONCLUSION This study has clarified the correlation between the clinical phenotypes of five children with LAMSHF and variants of the SOX5 gene, which expanded the mutational spectrum of the SOX5 gene and provided a basis for the clinical diagnosis and genetic counseling.
Humans ; Male ; Female ; Phenotype ; Child, Preschool ; Child ; SOXD Transcription Factors/genetics* ; Exome Sequencing ; Mutation ; Infant