Introduction: Multiple daily insulin injections, while effective for glycemic control, impose considerable costs on healthcare systems and carry inherent risks including hypoglycemia, weight gain, and poor treatment adherence. This study evaluates the glycemic effects of insulin regimen de-escalation from multiple daily injections in poorly controlled type 2 diabetes mellitus (T2DM) patients and explores the predictors of successful insulin de-escalation. Methodology: This is a multi-centred, prospective observational study of adult T2DM patients on multiple daily insulin injections with hemoglobin A1c (HbA1c) 7–12% who underwent de-escalation to one or two injections. Patients were reassessed at 3 months and 6 months. Primary endpoint was change in HbA1c from baseline. Secondary endpoints were changes in body weight, hypoglycemia frequency, treatment adherence and predictors of successful insulin de-escalation defined by at least a 0.3% reduction in HbA1c while on de-escalated regimen. Results: A total of 80 patients were included. HbA1c improved from 9.23 to 8.52% (p <0.001) with total daily insulin dose reduction from 0.81 + 0.35 units per kg to 0.46 + 0.24 units per kg. Symptomatic hypoglycemia decreased from 22.5 to 5.0%. Insulin adherence improved from 50.0 to 92.3%. Body weight decreased by 1.4 kg. Forty-nine patients (61.3%) were successfully de-intensified. Factors associated with successful insulin de-escalation included a high baseline HbA1c, high fasting blood glucose and higher estimated glomerular filtration rate, while increased age, disease duration and being Indian were associated with unsuccessful insulin de-escalation. After adjustment of the confounders, only HbA1c (OR 2.07, 95% CI 1.23–3.46, p = 0.006) and the status of being Indian (OR 0.21, 95% CI 0.05–0.94, p = 0.041) remained as significant positive and negative predictors respectively for successful insulin de-intensification. Conclusion Insulin regimen de-escalation, when combined with optimized oral glucose-lowering agents, improved glycemic control and treatment adherence while reducing hypoglycemia and body weight. These findings support insulin therapy deescalation as a safe, effective strategy for poorly controlled T2DM patients taking multiple daily insulin injections.
Diabetes Mellitus, Type 2 ; Prospective Studies ; Insulins

Introduction: Normotensive pheochromocytomas in Von Hippel-Lindau (VHL) syndrome present unique perioperative challenges. Standard alpha-blockade may induce intolerable orthostatic hypotension, making calcium channel blockers (CCB) a practical alternative. Furthermore, the primary intraoperative danger in these specific phenotypes may not be a hypertensive crisis, but profound vasoplegia. We report a VHL patient undergoing synchronous robotic surgery exhibiting this paradoxical hemodynamic response. Case: A 37-year-old female with VHL syndrome presented with an incidental 3.5-cm left adrenal mass and bilateral renal masses. Biochemistry confirmed a normotensive, noradrenergic pheochromocytoma (24-hour urine normetanephrines 4.2x upper limit of normal). Renal biopsy revealed a clear cell papillary renal cell tumor. Due to prior severe intolerance to Prazosin (hypotension/dizziness with low-dose Prazosin 0.5 mg ON), we utilized amlodipine for preoperative optimization. She was only able to tolerate low-dose 2.5 mg OD alongside oral sodium chloride and ample oral fluid loading. She underwent a synchronous robotic-assisted left adrenalectomy and left midpole renal tumor excision. Strikingly, tumor manipulation did not precipitate a hypertensive crisis. Instead, she developed hypotension requiring an intravenous noradrenaline infusion prior to adrenal vein ligation and tumor removal. Vasopressor support was successfully weaned 12 hours postoperatively, and she was discharged well. Conclusion Normotensive, noradrenergic pheochromocytomas in VHL are hemodynamically fragile. Chronic catecholamine excess induces homologous desensitization and downregulation of alpha-1 adrenergic receptors. This physiological adaptation explains the normotensive presentation and highlights the intraoperative vasoplegia experienced once sympathetic tone is altered by anesthesia. While CCB monotherapy with volume expansion safely facilitates prolonged, synchronous robotic surgeries, clinicians must anticipate and combat refractory hypotension rather than classical hypertensive spikes.

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 Warburg effect refers to a metabolic shift in which cells preferentially utilize aerobic glycolysis rather than oxidative phosphorylation despite adequate oxygen availability. This phenomenon is increasingly recognized as the mechanism for tumor-associated hypoglycemia, or paraneoplastic syndromes such as insulin-like growth factor-2 (IGF-2)– mediated non-islet cell tumor hypoglycemia. We present a case of Warburg effect with management challenges. Case: A 47-year-old male with advanced, treatment-naive retroviral disease presented with chronic cough, progressive right thigh swelling, constitutional symptoms over several months, followed by reduced responsiveness for 2 days prior to admission. Clinically, he was delirious, cachectic with generalized lung crepitations and right thigh mass. He was diagnosed with smear-negative disseminated tuberculosis, and thigh mass was considered either a tuberculous granuloma or sarcoma. During hospitalization, he developed recurrent hypoglycemia with lactatemia despite intravenous dextrose, optimized enteral feeding and a 1-day course of intravenous octreotide. His blood investigations showed full blood count, renal function test, liver function test, and serum ketone within normal range. His arterial blood gas analysis showed type B lactic acidosis with persistent lactatemia. At the time of hypoglycemia (RBS: 3.1 mmol/L), his serum insulin was suppressed, C-peptide was low–normal, morning cortisol was elevated, and IGF-1 was markedly reduced suggestive of non-insulin-mediated hypoglycemia secondary to Warburg effect. Conclusion In patients with retroviral disease and tuberculosis, Warburg effect may lead to poorer clinical outcomes and management may be challenging. Thus, definitive antimicrobial therapy with second generation somatostatin analogues (Pasireotide) may be considered in selected cases to modulate dysregulated hormonal and metabolic pathways. Early identification and timely targeted intervention are crucial to improving outcomes in this high-risk population.
Persistent Infection ; Hypoglycemia

Introduction: Cushing’s disease in adolescents is rare and frequently difficult to diagnose due to overlapping features with common pubertal and metabolic conditions. We present an adolescent who underwent inferior petrosal sinus sampling (IPSS) with possible cyclical Cushing’s disease, highlighting the diagnostic challenges and the interpretive value of IPSS. Case: A 16-year-old female presented with progressive weight gain, acne, hirsutism, secondary amenorrhea, proximal myopathy, violaceous striae, and facial plethora over 1 year. Her 24-hour urinary cortisol was >3,310 nmol/L with failure of suppression following a 1-mg overnight dexamethasone suppression test (701 nmol/L). Her adrenocorticotropic hormone (ACTH) was raised (77.9 pg/mL), consistent with ACTH-dependent Cushing syndrome. Her hemoglobin A1c was 5.9%, and she has low bone mass for age with a Z score of -2.9 at the Lumbar spine. Pituitary magnetic resonance imaging identified a rightsided microadenoma measuring 0.6 × 0.5 cm, while computed tomography of the thorax, abdomen, and pelvis showed no ectopic source. IPSS with desmopressin stimulation was performed to confirm the ACTH source. No steroidogenesis inhibitors were administered prior to testing. Notably, cortisol levels during IPSS were relatively low, with midnight cortisol of 91 nmol/L and morning cortisol of 200 nmol/L, suggesting testing during a trough phase of possible cyclical hypercortisolism. Despite this, IPSS demonstrated a significant central-to-peripheral ACTH gradient supporting a pituitary source. Conclusion This case highlights the diagnostic dilemma of interpreting IPSS in suspected cyclical Cushing’s disease. Fluctuating cortisol secretion may result in discordant biochemical findings and complicate localization studies. IPSS findings should be interpreted cautiously and integrated with clinical features, imaging, and serial biochemical monitoring. Recognition of cyclical disease patterns is essential to ensure appropriate management in adolescent patients.
Adolescent ; Humans ; Petrosal Sinus Sampling

Introduction: Acromegaly is an endocrine disorder caused by excess growth hormone (GH), causing somatic overgrowth, multiple comorbidities, and premature mortality. It is confirmed biochemically by an elevated GH level, which is not suppressed post oral glucose tolerance test (OGTT). The serum level of insulin-like growth factor-1 (IGF-1) is recommended for diagnosis, monitoring, and screening, and a normal level effectively excludes the disease. We report a patient with acromegaly who presented with normal IGF-1. Case: A 21-year-old female, with no known medical illness, presented with a persistent, progressive headache and amenorrhea for the past 6 months. She also noticed a change in facial appearance and an increase in the size of her hands and feet. Blood parameters revealed raised GH level of >50 ng/mL, normal IGF-1 30.3 nmol/L (12.17–44.80), mildly raised prolactin 692 mIU/L, low am cortisol 62 nmol/L (166–507), thyroid-stimulating hormone of 0.63 mIU/L (0.27–4.20), free thyroxine 4 11 pmol/L (12–22), low follicle-stimulating hormone 0.90 IU/L, luteinizing hormone <0.30 IU/L, estradiol <18.4 pmol/L, and fasting blood sugar of 17.7 mmol/L with hemoglobin A1c 9%. In view of normal IGF-1 with a high index of suspicion for acromegaly, she underwent OGTT which showed unsuppressed GH. Magnetic resonance imaging pituitary showed sellar mass 2.4 × 2.9 × 2.1 cm with suprasellar extension as well as extension into the right cavernous sinus, suggestive of pituitary macroadenoma. She was diagnosed with acromegaly with secondary adrenal insufficiency and central hypothyroidism with hypogonadotropic hypogonadism, complicated with poorly controlled diabetes. She was started on thyroxine and hydrocortisone replacement and required basal bolus insulin of 1.3 u/kg/day. Repeated IGF-1 showed a raised value, 85.4 nmol/L, after optimization of diabetes. She underwent endoscopic transsphenoidal surgery with normalization of blood sugar post-surgery. Blood pressure was normal throughout. Conclusion False negative or normal IGF-1 levels may result in patients with hepatic or renal failure, hypothyroidism, malnutrition, use of oral estrogen, severe infection, and poorly controlled diabetes mellitus. Hence, a low or normal IGF1 does not exclude acromegaly in patients with a high index of suspicion and warrants further investigation.
Acromegaly ; Insulin-Like Growth Factor I

Introduction: Polycystic ovary syndrome (PCOS) is the most common cause of hyperandrogenism in women of reproductive age. However, several endocrine disorders, particularly Cushing disease (CD), can closely mimic the clinical, biochemical, and radiological features of PCOS. This overlap may lead to misdiagnosis and delayed recognition of hypercortisolism, with significant metabolic and reproductive consequences. Case: We report a 24-year-old female with young-onset diabetes mellitus who was referred for endocrine co-management during admission for recurrent mons pubis and labial abscesses with poorly controlled glycemia. She had a 5-year history of progressive hirsutism, oligomenorrhoea, scalp hair loss, significant weight gain, and insulin resistance, and had previously been labelled as having PCOS during adolescence, with subsequent default of follow-up. On examination, she was obese (body mass index 33 kg/ m²) with plethoric facies, acanthosis nigricans, proximal myopathy, and hirsutism (Ferriman–Gallwey score 10), without overt virilization or acromegalic features. Biochemical evaluation demonstrated severe hyperandrogenism with markedly elevated total testosterone (7.05 nmol/L), suppressed gonadotropins, and adrenocorticotropic hormone (ACTH)-dependent hypercortisolism. Cortisol failed to suppress on low-dose dexamethasone testing, and 24-hour urinary free cortisol was markedly elevated (>4,900 nmol/24 h). Pelvic ultrasonography and computed tomography imaging showed polycystic ovarian morphology without evidence of an ovarian mass. Pituitary magnetic resonance imaging revealed a small right-sided pituitary microadenoma measuring 2.6 × 3.7 mm. Inferior petrosal sinus sampling demonstrated a central-to-peripheral ACTH gradient with adequate prolactin ratios, confirming pituitary CD. Conclusion This case highlights how Cushing disease can closely mimic PCOS, including polycystic ovarian morphology and hyperandrogenism. Progressive symptoms, severe biochemical androgen excess, and marked insulin resistance should prompt evaluation for secondary causes of hyperandrogenism, particularly hypercortisolism, to avoid delayed diagnosis and prolonged morbidity.
Female ; Hyperandrogenism ; Pituitary ACTH Hypersecretion ; Polycystic Ovary Syndrome

Introduction: Acromegaly is usually diagnosed by elevated age- and sex-adjusted insulin-like growth factor-1 (IGF-1) levels reflecting chronic growth hormone (GH) excess. IGF-1 is preferred as a screening biomarker due to its longer half-life and reduced pulsatility compared with GH. However, IGF1 levels may be disproportionately low or only modestly elevated in certain clinical contexts, leading to diagnostic uncertainty. Pituitary apoplexy is one such condition in which acute tumor hemorrhage or infarction may disrupt sustained GH secretion and attenuate IGF-1 production Case: A 48-year-old female with hypertension, type 2 diabetes mellitus, and dyslipidemia presented with a 2-day history of severe headache, vomiting, and visual disturbance, on a background of progressive acral enlargement over 2 years. Examination revealed coarse facial features, prognathism, enlarged hands, and cranial nerve involvement. Magnetic resonance imaging demonstrated an invasive sellar– suprasellar pituitary macroadenoma with optic chiasmal compression and cavernous sinus encasement. Intravenous dexamethasone was initiated pre-operatively due to a significant mass effect. Biochemical evaluation showed markedly elevated random GH levels (>50 ng/mL) with only mildly elevated IGF-1 at 1.19 times the upper limit of normal, below the threshold at which confirmatory oral glucose tolerance testing may be omitted according to current guidelines. Other pituitary axes suggested evolving hypopituitarism. During admission, she developed severe hyperglycemia with marked insulin resistance, requiring high-dose insulin therapy (approximately 1.5 U/kg/day). She underwent urgent transsphenoidal surgery, with histopathology confirming a pituitary neuroendocrine tumor with extensive hemorrhage and infarction, consistent with pituitary apoplexy. Postoperatively, GH levels were suppressed to <5 ng/mL, insulin requirements decreased markedly, and hormone replacement was initiated for secondary adrenal insufficiency and central hypothyroidism. Conclusion This case highlights that IGF-1 levels below conventional diagnostic thresholds do not exclude clinically significant acromegaly, particularly in the setting of pituitary apoplexy. Integration of clinical phenotype, GH levels, and imaging findings is essential to avoid diagnostic delay and ensure timely management.
Acromegaly ; Insulin Resistance ; Pituitary Apoplexy

Objective: The primary objective was to assess beta-cell function of recently-diagnosed young-onset type 2 diabetes mellitus (T2DM) individuals using basal and stimulated C-peptide levels. The secondary objective was to examine the association between C-peptide with metabolic factors and diabetes complications. Methodology: A cross-sectional study was conducted for young-onset T2DM individuals aged 18-35 years with a disease duration of not more than 5 years. Plasma C-peptide was measured before and after intravenous glucagon injection. Demographic data, medical history and complications were obtained from medical records and clinical assessment. Continuous data were expressed as median and interquartile range (IQR). Categorical variables were described as frequency or percentage. Multivariable linear regression analysis was used to determine factors associated with C-peptide levels. Results: 113 participants with young-onset T2DM with a median (IQR) age of 29.0 (9.5) years and 24 (36) months were included in this study. The median (IQR) basal and stimulated C-peptide was 619 (655) pmol/L and 1231 (1024) pmol/L. Adequate beta-cell function was present in 78-86% of the participants based on the basal and stimulated C-peptide levels. We found hypertension, obesity and diabetic kidney disease (DKD) to be independently associated with higher C–peptide levels. In contrast, females, smokers, those on insulin therapy and with longer duration of disease had lower C–peptide levels. Conclusion Most recently diagnosed young-onset T2DM have adequate beta-cell function. Elevated C-peptide levels associated with obesity, hypertension and diabetic kidney disease suggest insulin resistance as the key driving factor for complications.
Diabetes Mellitus, Type 2 ; C-Peptide

Ganglioneuromas (GNs) are benign tumors that originate from neural crest cells, composed mainly of mature ganglion cells. These tumors, which are usually hormonally silent, tend to be discovered incidentally on imaging tests and occur along the paravertebral sympathetic chain, from the neck to the pelvis and occasionally in the adrenal medulla. Rarely, GNs secrete catecholamines.1 Adrenal GNs occur most frequently in the fourth and fifth decades of life, whereas GNs of the retroperitoneum and posterior mediastinum are usually encountered in younger adults.2 Adrenal GNs are commonly hormonally silent and asymptomatic; even when the lesion is of substantial size.3We report an incidentally detected asymptomatic case of an adrenal ganglioneuroma with mildly elevated urinary catecholamine levels in an elderly male. After preoperative alpha blockade, the patient underwent open right adrenalectomy. Upon microscopic examination, the right adrenal mass proved to be a ganglioneuroma, maturing type and the immunohistochemistry examination showed immunoreactivity to synaptophysin, chromogranin, and CD 56, while S100 was strongly positive at the Schwannian stroma. Following resection, catecholamine levels normalized, confirming the resected right adrenal ganglioneuroma as the source of the catecholamine excess. This case represents a rare presentation of catecholamine-secreting adrenal ganglioneuroma in the elderly.
Adrenal Glands ; Catecholamines ; Ganglioneuroma