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: The identification of a significant adrenal mass in a patient without a biopsy-confirmed malignancy poses a diagnostic challenge: Is it a metastatic lesion or an underlying adrenal condition? Adrenal metastases are the second most common site of spread for lung adenocarcinoma; approximately 3–7% of adrenal masses represent benign adenomas. Diagnosis is even harder if there are signs of primary aldosteronism (PA). Case: We present a case of a 62-year-old Chinese female with a 10-year history of hypertension, managed on dual antihypertensive therapy, who presented for evaluation of suspected PA following the discovery of hypokalemia. Biochemical screening revealed an elevated aldosteronerenin ratio (ARR, 65). The overnight dexamethasone suppression test (20 nmol/L) and testosterone (0.79 nmol/L) were both within normal limits. Saline Suppression Test (SST) showed an indeterminate post-infusion aldosterone level (202.8 pmol/L). Cross-sectional imaging via computed tomography (CT) Adrenals identified a large, 6.4 × 5.4 × 6.2 cm heterogeneous left suprarenal mass with a low mean attenuation (8.6 Hounsfield Unit [HU]). Concurrently, an incidental left upper lobe pulmonary lesion was identified, and PET-CT was performed; the SUVmax of the lung was identical to that of the adrenal lesion. An ultrasoundguided biopsy of the pulmonary lesion confirmed estimated glomerular filtration rate-mutation-positive lung adenocarcinoma. The patient started on targeted therapy with dacomitinib. Follow-up CT imaging at 9 months demonstrated disease progression within the thorax, marked by the appearance of a new pulmonary nodule. Notably, however, the adrenal mass remained stable in size and morphology. Conclusion The absence of mixed androgen/glucocorticoid hypersecretion, combined with the radiographically static nature of the mass, suggests a lower probability of adrenocortical carcinoma. This case highlights that while size is a major risk factor for adrenocortical carcinoma, it must be interpreted in conjunction with hormonal activity, HU, and growth patterns. Identifying these “mimics” helps avoid over-staging lung cancer and ensures patients receive targeted therapy instead of unnecessary adrenalectomies.

Introduction: Insulin deintensification is an emerging strategy to reduce hypoglycemia and treatment burden in patients on multiple daily injection (MDI ≥3), with potential to improve adherence and glycemic control. However, evidence in poorly controlled type 2 diabetes mellitus (T2DM) remains limited. This study evaluated its effectiveness and identified factors associated with achieving adequate glycemic control following deintensification among patients with poorly controlled T2DM attending Malaysian primary care. Methodology: A retrospective cohort study was conducted among 107 T2DM patients with hemoglobin A1c (HbA1c) >9%, attending Enhanced Diabetic Clinic at Cheras Health Clinic between 2021 and 2025. All patients on basal-bolus insulin (BBI) underwent deintensification. Multivariate logistic regression was performed to identify factors associated with achieving adequate glycemic control (HbA1c <7.5%). Changes in HbA1c following deintensification were assessed using paired t-tests. Results: Overall, 50.5% of patients achieved adequate glycemic control. Hypoglycemia events (AOR 9.5, 95% confidence interval [CI] 1.6–58.3; p = 0.015), MDI (AOR 9.6, 95% CI 1.4–67.1; p = 0.023) and Diabetes Medication Therapy Adherence Clinic (DMTAC) visits (AOR 1.1, 95% CI 1.0– 1.2; p = 0.039) were significantly associated with achieving HbA1c <7.5%. Conversely, patients transitioned from BBI to premixed regimens were less likely to achieve HbA1c <7.5% (AOR 0.22, 95% CI 0.05–0.93, p = 0.039). All insulin deintensification strategies were associated with significant HbA1c improvements with transitioned from BBI to premixed human insulin (mean difference -2.54%, 95% CI 1.77–3.31, p <0.001, Cohen’s d = 1.09), BBI to premixed analogue insulin (mean difference -3.38%, 95% CI 2.26– 4.49, p <0.001, Cohen’s d = 1.62), BBI to basal insulin (mean difference -3.67%, 95% CI 1.79–5.54, p = 0.004, Cohen’s d = 2.05). Conclusion Insulin deintensification is an effective strategy for improving glycemic control in poorly controlled T2DM. These findings highlight the importance of deintensification with careful consideration of hypoglycemia, MDI-related treatment burden, and patient engagement through regular DMTAC visits, which are integral to achieving optimal outcomes and support a personalized approach to diabetes management in primary care.
Diabetes Mellitus, Type 2 ; Glycemic Control ; Retrospective Studies ; Primary Health Care ; Insulins

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

Ascaridia galli infection compromises the health and productivity of chickens. this study aimed to determine the prevalence, pathology, and control of A. galli in backyard chickens. Four hundred and fifty-six faecal samples were tested using direct smear and concentration techniques. sixty chickens were grouped based on egg per gram into untreated control, mebendazole-treated, and derivative-treated. Key epidemiologic host based and environmental variables were recorded and analysed statistically (p < 0.05 significance level). Histopathological changes in the intestine were also assessed. Overall prevalence of A. galli was 72% (330/456). Infection was high in females (74%, 200/267) than in males (68%, 130/189). Adult chickens had a higher infection rate than young (64% vs 55%; p < 0.05). Weak chickens showed a markedly higher prevalence (96%, 150/156) than healthy chickens (60%, 180/300) (p < 0.05). Geographically, prevalence was highest in Swat (85.53%), followed by Lower Dir (72.3%) and Malakand (59.21%), with statistically significant differences (p < 0.05). Management system influenced infection: free range chickens had (63%) compared to semi-free range (37%), scavenging chickens were more infected (75%) compared to receiving supplemental feed (53%) (p < 0.05). The non-dewormed chickens had a significantly higher prevalence (92%) than the dewormed group (20%) (p < 0.05). Seasonal infection peaked during the rainy season (86%) compared to the dry season (44%) (p < 0.05). Intestinal histology revealed inflammation, epithelial necrosis, villous atrophy, and crypt hyperplasia. Treatment of the chickens nematodes using mebendazole resulted in 70% (14/20) of the treated eggs being egg-negative, and the comparison of treatment of the egg-negative derivative compound resulted in 80% (16/20) of the treated eggs being egg-negative. The A. galli infection are very common, and cause intestine damage. The mebendazole and its derivative decrease egg shedding significantly, Husbandry, management and treatment should be enhanced for effective control strategies.

Introduction: Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder that significantly affects adolescent girls, particularly those with overweight or obesity. However, data examining the determinants and metabolic profiles of PCOS among adolescents with overweight and obesity remain limited, especially in Malaysia. This protocol describes a case-control study investigating the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. Methodology: This study is designed as a case-control study involving adolescent girls aged 13–16 years with a body mass index z-score >+1 standard deviation. Cases are defined as adolescent girls with a confirmed diagnosis of PCOS based on the recommendations of the 2017 International Consortium of Paediatric Endocrinology (ICPE), while controls are those who do not meet the diagnostic criteria for PCOS. A total sample size of 440 participants is required. Participants will be recruited from 22 secondary schools selected from a list of schools in Kuala Lumpur. Data on sociodemographic characteristics, psychosocial health, physical activity, and dietary intake will be collected using structured questionnaires. Blood samples will be obtained and analyzed for diagnostic testing (free testosterone), exclusion tests (thyroid-stimulating hormone, folliclestimulating hormone, luteinizing hormone, estradiol, prolactin, and dehydroepiandrosterone sulfate), and biochemical parameters (liver function tests, lipid profile, hemoglobin A1c, fasting glucose, fasting insulin, and inflammatory markers). Results: The study is expected to generate comprehensive data on the cardiometabolic, dietary, and psychosocial determinants of PCOS among adolescents with overweight and obesity. The findings will inform early screening strategies and targeted interventions aimed at reducing long-term reproductive and cardiometabolic complications. Conclusion This protocol outlines a structured approach to investigating PCOS in adolescence and addresses current gaps in early identification and risk stratification among highrisk populations.
Adolescent ; Humans ; Case-Control Studies ; Overweight ; Polycystic Ovary Syndrome ; Obesity

Introduction: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal chromaffin cells, with an estimated incidence of 2–8 cases per million per year. These tumors originate from neural crest–derived cells of the sympathetic and parasympathetic paraganglia and may secrete catecholamines, resulting in malignant hypertension or symptoms such as headache, palpitations, and diaphoresis. They can occur anywhere along the paravertebral and para-aortic regions from the skull base to the pelvic floor. Case: We report a case of a 14-year-old male with no known premorbid conditions who presented with presyncope and a 1-month history of headache. On examination, he had severe hypertension (242/167 mmHg), tachycardia (127 bpm), and grade IV hypertensive retinopathy. Investigations showed preserved renal function with markedly elevated 24-hour urinary metanephrines (normetanephrine 90.75 µmol/L). Computed tomography revealed a lobulated, heterogeneously enhancing mass measuring 5.0 × 6.1 × 5.4 cm along the left margin of the abdominal aorta at the infrarenal level, suggestive of an extra-adrenal lesion. Gallium-68 PET scan demonstrated a somatostatin receptor–avid left peritoneal mass. The patient underwent exploratory laparotomy and tumor excision, complicated intraoperatively by blood pressure lability requiring nitroprusside and inotropic support. Postoperatively, he improved significantly and was able to wean off all antihypertensive medications. Histopathology confirmed left retroperitoneal paraganglioma. Conclusion Primary peritoneal paraganglioma is a rare but important cause of secondary hypertension, especially in young patients presenting with hypertensive emergency. High index of suspicion is essential for early diagnosis. Management requires a multidisciplinary approach with careful preoperative optimization to minimize perioperative complications. Surgical resection remains the definitive treatment and, as demonstrated in this case, can result in marked clinical improvement with resolution of hypertension.
Paraganglioma

Introduction: Brown tumors, also known as osteitis fibrosa cystica, are focal bone lesions resulting from increased osteoclastic activity and fibroblastic proliferation. They represent a rare complication of uncontrolled hyperparathyroidism (HPT) and may affect any part of the skeleton, including craniofacial bones. Case: We report a case of a 31-year-old Malay female diagnosed with primary HPT secondary to multiglandular disease, who initially presented with symptomatic hypercalcemia. Biochemical evaluation revealed elevated corrected calcium (2.84 mmol/L; reference range 2.2–2.6 mmol/L), low phosphate (0.63 mmol/L; reference range 0.8–1.6 mmol/L), and markedly elevated serum intact parathyroid hormone (iPTH) (286 pg/mL; reference range 14.9–56.9 pg/mL). Ultrasound parathyroid showed a large right extrathyroidal lesion, most likely suggestive of parathyroid adenoma, where sestamibi scan suggested multiglandular parathyroid adenomas with possible mediastinal involvement. She underwent exploratory parathyroidectomy on 19 June 2024, with excision of bilateral inferior parathyroid adenomas confirmed on histopathology. Despite surgery, she had persistent hypercalcemia (2.8–3.1 mmol/L) and rising iPTH levels (307 pg/mL on 24 June 2024, increasing to 413 pg/mL by 2 September 2024), consistent with persistent disease. Repeat imaging demonstrated hyperfunctioning parathyroid tissue in the anterior mediastinum. Subsequently, the patient developed progressive enlargement of the left upper gingiva associated with significant pain during mastication. Clinical and radiological evaluation revealed aggressive lesions with cortical expansion. Excisional biopsy of the gingival lesion confirmed the diagnosis of brown tumors involving the jaws. She later underwent a second parathyroidectomy with intraoperative parathyroid hormone monitoring at another centre. Postoperatively, normalization of serum calcium and iPTH levels was achieved, which led to marked clinical improvement and regression of the craniofacial brown tumor. Conclusion This case highlights that skeletal manifestations of HPT, including brown tumors, may regress following adequate biochemical control without additional local therapy. Early recognition and definitive surgical management of persistent or ectopic hyperfunctioning parathyroid tissue are essential to prevent progression and promote spontaneous bone healing processes.

Introduction: Atypical parathyroid adenoma is a rare cause of primary hyperparathyroidism and represents a borderline entity between benign adenoma and parathyroid carcinoma. Due to overlapping clinical, biochemical, and imaging features with carcinoma, diagnosis can be challenging and relies on histopathological evaluation to guide management and follow-up. Case: A 25-year-old male presented with a 3-month history of generalized bone pain and lethargy, with significant weight loss of 17 kg over 7 months. He denied headache, visual disturbance, or hypoglycemic episodes. There was no known family history of endocrine tumors. Examination revealed a palpable right-sided neck mass. Biochemical evaluation showed severe primary hyperparathyroidism with marked hypercalcemia (4.12 mmol/L), hypophosphatemia (0.6 mmol/L), markedly elevated intact parathyroid hormone (137 pmol/L) and alkaline phosphatase (1,958 U/L). Thyroid function was normal. Neck ultrasound demonstrated a right TIRADS 4 lesion, and fine-needle aspiration suggested parathyroid tissue. Sestamibi scan localized a hyperfunctioning right inferior parathyroid gland measuring 2.1 × 1.7 × 3.3 cm. During admission, he sustained low-impact fragility fractures of the left femur and humerus after a fall. Preoperatively, management of hypercalcemia proved challenging. Despite aggressive medical therapy and intensive intravenous hydration with up to 6 liters of normal saline per day, serum calcium levels remained persistently exceeding 3.0 mmol/L. He underwent right hemithyroidectomy with excision of the right inferior parathyroid gland. The postoperative course was complicated by hungry bone syndrome, necessitating intravenous calcium gluconate infusion for 1 week. Histopathological examination confirmed the diagnosis of an atypical parathyroid adenoma. On postoperative follow-up, serum calcium and phosphate levels normalized while he remained on calcium carbonate and calcitriol supplementation. Conclusion Severe primary hyperparathyroidism in young patients may indicate aggressive parathyroid pathology. Atypical parathyroid tumors can mimic carcinoma, and diagnosis requires histopathology with long-term follow-up due to uncertain malignant potential.
Carcinoma ; Adenoma

Introduction: Pituitary stalk interruption syndrome (PSIS) is a rare congenital disorder characterized by the neuroradiological triad of an absent or interrupted pituitary stalk, ectopic posterior pituitary, and anterior pituitary hypoplasia. It is typically diagnosed in infancy or childhood due to growth failure or delayed puberty. Diagnosis in adulthood is uncommon and may occur after decades of untreated hypopituitarism. Case: A 34-year-old Malay male with underlying physical and intellectual disability presented after a mechanical fall resulting in left slipped capital femoral epiphysis, an unusual pathological fracture in adulthood. Clinical examination revealed marked infantilism with complete absence of secondary sexual characteristics (Tanner stage I). Laboratory evaluation demonstrated combined pituitary hormone deficiency, including severe central hypothyroidism, profound hypogonadotropic hypogonadism, and central adrenal insufficiency. Growth hormone and insulin-like growth factor 1 were undetectable, while prolactin was mildly elevated, consistent with pituitary stalk disruption due to loss of hypothalamic dopaminergic inhibition. Bone age assessment showed severe delay, corresponding to 15 years. Pituitary magnetic resonance imaging demonstrated the classical PSIS triad: anterior pituitary hypoplasia with partial empty sella, a high T1 signal nodule at the median eminence representing ectopic posterior pituitary, and non-visualization of the infundibulum, consistent with an absent pituitary stalk. Birth history revealed premature breech delivery, a recognized perinatal risk factor. The patient was commenced on hormone replacement therapy, including levothyroxine, hydrocortisone, testosterone undecanoate, and calcium–vitamin D supplementation. Conclusion This case illustrates that PSIS may remain undiagnosed into adulthood, leading to severe consequences of long-standing hypopituitarism such as osteoporosis and pathological fractures. Clinicians should consider hypopituitarism in adults presenting with unexplained fractures and delayed sexual maturation, particularly when supported by a suggestive perinatal history.
Fractures, Spontaneous ; Pituitary Gland