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: Adrenocortical carcinoma (ACC) is an aggressive malignancy with high rates of recurrence even after surgical resection. Surgery remains the mainstay of treatment, while adjuvant options are limited. Mitotane is the only approved systemic therapy. Current guidelines recommend stereotactic body radiotherapy (SBRT) alongside adjuvant mitotane therapy in Rx, R1, R2 resections and in locally advanced disease. Case: We present a case of a 40-year-old female who presented with abdominal pain and was found to have a large heterogeneous left adrenal mass measuring 8.2 × 8.5 × 9.5 cm (Hounsfield Unit 63) on computed tomography (CT) imaging. Clinically, she was obese with a body mass index of 33.7 kg/m². No discriminatory feature of Cushing’s was present. Hormonal evaluation demonstrated autonomous cortisol secretion with failure of suppression on both overnight and low-dose dexamethasone suppression tests at 301 nmol/L and 313.6 nmol/L, respectively. DHEA, testosterone, and urinary metanephrine were within range. Hemoglobin A1c was 6.6%. She underwent open left adrenalectomy. Intra-operatively, a 12 × 10 cm adrenal tumor was identified with multiple areas of tumor rupture and spillage during mobilization. HPE confirmed high-grade ACC with high Weiss score of 8, Ki-67 index 60–80%, and mitotic count 54/50 hpf (pT2Nx). Post-operative CT imaging demonstrated a residual soft tissue lesion in the left adrenal bed (largest diameter 3.8 cm) with fluorodeoxyglucose avidity. We commenced adjuvant mitotane therapy, titrated to 2 g TDS with supraphysiological hydrocortisone replacement. Mitotane level was within therapeutic range (16 mcg/mL). She was deemed unsuitable for repeat surgery due to the proximity of the residual mass to the adjacent vessel and was planned for SBRT therapy after a multidisciplinary team discussion. Conclusion High-risk ACC with suspected residual disease remains a therapeutic challenge. While mitotane remains the cornerstone of adjuvant therapy, SBRT may represent a promising adjunctive local treatment modality in carefully selected patients. Further studies are required to define its role in improving local control and outcomes in ACC.
Adrenocortical Carcinoma ; Mitotane

Introduction: Permanent hypoparathyroidism is a recognized complication of total thyroidectomy, with an estimated incidence of 10.47%. Standard treatment involves supplementation with calcium and activated vitamin D. However, some patients remain refractory to conventional therapy and fail to achieve normocalcemia. During pregnancy, significant physiological changes occur in calcium-regulating hormones. Notably, the placenta increases the production of parathyroid hormone-related peptide (PTHrP), which acts as a calcitropic hormone, mimicking the effects of parathyroid hormone. Case: A 38-year-old female with a history of total thyroidectomy 14 years ago for follicular thyroid carcinoma presented with permanent hypoparathyroidism. Her condition was refractory to high-dose replacement therapy, which included calcium carbonate 3 g BD, alfacalcidol 4 mcg ON, calcitriol 1 mcg BD, and cholecalciferol 100,000 IU OD. Despite compliance, her serum calcium levels fluctuated between 1.7 and 1.93 mmol/L, necessitating intermittent intravenous calcium infusions. Laboratory investigations showed a phosphate level of 1.63 mmol/L and 24-hour urine calcium of 4.81 mmol/L. Her thyroid function remained stable on levothyroxine 150 mcg daily (T4: 12.0 pmol/L; thyroid-stimulating hormone: 2.93 mIU/L). While off-label use of teriparatide was being considered, she became pregnant. As the pregnancy progressed, her calcium levels stabilized. Calcitriol was discontinued at 26 weeks’ gestation when her calcium reached 2.5 mmol/L. By 30 weeks, the alfacalcidol dose was reduced to 3.5 mcg daily, with cholecalciferol dosing reduced to 50,000 IU OD. Her corrected calcium levels remained between 2.4 and 2.6 mmol/L until delivery. Similar reduction in supplementation requirements was noted during her previous pregnancy. Conclusion Elevated PTHrP during pregnancy likely contributed to improved calcium homeostasis by increasing maternal bone resorption and enhancing placental calcium transfer. This case underscores the necessity of individualized, dynamic adjustments to calcium and vitamin D therapy based on rigorous biochemical monitoring for pregnant patients with hypoparathyroidism.
Female ; Pregnancy ; Hypoparathyroidism ; Placenta

Introduction: Immunoglobulin G4-related hypophysitis (IgG4-RH) is a rare fibro-inflammatory disorder affecting the pituitary gland. Glucocorticoids remain the first-line therapy, but their use may be complicated in patients with significant metabolic comorbidities. We report a case of suspected IgG4-RH presenting with hyperosmolar hyperglycemic state (HHS), highlighting the challenges of balancing disease control against glucocorticoid metabolic toxicity adverse effects. Case: A 32-year-old female with obesity and newly diagnosed diabetes mellitus was admitted with HHS. Prior to admission, she reported weight fluctuations, episodic headaches, progressive visual disturbance, and secondary amenorrhea. Following resolution of HHS, persistent polyuria of 10–16 L/day prompted further evaluation and led to a diagnosis of arginine vasopressin deficiency. Anterior pituitary hormonal work-up revealed hypogonadotropic hypogonadism. Pituitary magnetic resonance imaging demonstrated infundibular thickening measuring 0.5 cm, with concomitant marked bilateral parotid enlargement. Serum IgG4 was elevated at 2.26 g/L (0.63–2.01), raising strong suspicion for IgG4-RH with systemic involvement. Histopathological confirmation from the parotid gland biopsy was consistent with sialadenosis. She was commenced on sublingual desmopressin and cyclical sex hormone replacement therapy. Given the provisional diagnosis of IgG4-RH, oral prednisolone 40 mg daily was initiated as a reduced induction regimen. However, treatment was poorly tolerated, with rapid weight gain from 93 to 100 kg and worsening glycemic control. Prednisolone was therefore tapered rapidly to 10 mg daily. Repeat imaging demonstrated interval improvement in infundibular thickening, but no functional endocrine recovery was observed. Conclusion This case illustrates the therapeutic challenge of managing IgG4-RH in the setting of pre-existing metabolic syndrome. Although glucocorticoids are effective for induction, their metabolic adverse effects may significantly restrict treatment tolerability. Early consideration of steroidsparing agents, such as rituximab or azathioprine, may be important to achieve remission while minimizing glucocorticoid-related adverse effects.
Autoimmune Hypophysitis

Introduction: Short stature and delayed puberty characterize Turner syndrome (TS). The 2024 international clinical practice guidelines recommend growth hormone (GH) for latediagnosed patients if epiphyses remain open. For patients with remaining growth potential, initiating GH alongside low-dose estrogen effectively balances linear growth with the need for timely pubertal induction. Case: A 15-year-old female, born prematurely at 6 months gestation, presented with delayed puberty, primary amenorrhea, and short stature. Examination revealed a height of 122 cm (<5th percentile), weight of 26 kg, with no syndromic facies, and Tanner stage 1. Investigations confirmed hypergonadotropic hypogonadism. Metabolic screening, including thyroid, renal, and liver profile, was normal. Her baseline insulin-like growth factor 1 (IGF-1) was low at 117.5 ng/mL (127.5–541.5). Karyotyping confirmed mosaic TS (45,X/46,Xr). Her skeletal bone age was delayed at 12 years, indicating a viable window for linear growth prior to complete epiphyseal fusion. Subcutaneous GH was initiated at 0.3 mg up titrated to 1.2 mg (0.45 µg/kg) daily over 4 weeks, then 1.35 mg (50 µg/kg) daily at month 5. Low-dose oral estradiol (0.5 mg three times weekly) was introduced for pubertal induction at month 4. After 9 months of combined GH and estrogen therapy, the patient achieved a height increment of 6 cm, reaching 128 cm without an adverse event. To achieve the clinical target of a 10–15 cm increment in the first year, her GH dose was further increased to 1.50 mg (55 µg/kg) daily. She showed an appropriate biochemical response with IGF-1 increased to 40.2 nmol/L (16.4–67.8) with a total height gain of 6 cm over the first 9 months of GH therapy. Conclusion Concomitant GH and estrogen therapy in late-diagnosed TS successfully induced clinically significant height gain. This dual approach maximized the limited window for linear growth, without delaying pubertal induction and compromising patient’s psychosocial well-being.
Turner Syndrome

Purpose: Total neoadjuvant therapy (TNT) is becoming the standard of care for locally advanced rectal cancer. However, surgery is deferred for months after completion, which may lead to fibrosis and increased surgical difficulty. The aim of this study was to assess whether TNT (TNT-RAPIDO) is associated with increased difficulty of total mesorectal excision (TME) compared with long-course chemoradiotherapy (LCRT) and upfront surgery. Methods: Twelve laparoscopic videos of low anterior resection with TME for rectal cancer were prospectively collected from January 2020 to October 2021, with 4 videos in each arm. Seven colorectal surgeons assessed the videos independently, graded the difficulty of TME using a visual analog scale and attempted to identify which category the videos belonged to. Results: The median age was 67 years, and 10 patients were male. The median interval to surgery from radiotherapy was 13 weeks in the LCRT group and 24 weeks in the TNT-RAPIDO group. There was no significant difference in the visual analog scale for difficulty in TME between the 3 groups (LCRT, 3.2; TNT-RAPIDO, 4.6; upfront, 4.1; P=0.12). A subgroup analysis showed similar difficulty between groups (LCRT 3.2 vs. TNT-RAPIDO 4.6, P=0.05; TNT-RAPIDO 4.6 vs. upfront 4.1, P=0.54). During video assessments, surgeons correctly identified the prior treatment modality in 42% of the cases. TNT-RAPIDO videos had the highest recognition rate (71%), significantly outperforming both LCRT (29%) and upfront surgery (25%, P=0.01). Conclusion TNT does not appear to increase the surgical difficulty of TME.

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

Levothyroxine remains the standard therapy for patients with hypothyroidism worldwide. Levothyroxine allergy is rarely seen and alternative therapies are less efficacious and scarcely available. The use of liothyronine (LT3) monotherapy is less favoured due to its short half-life and unpredictable pharmacological profile. We report a 59-year-old male with a hypersensitivity reaction to levothyroxine who was successfully desensitized with oral levothyroxine within a day using a 14-step protocol.
Thyroxine ; Hypersensitivity ; Hypothyroidism

Introduction: Prediabetes, typically defined as blood glucose levels above normal but below diabetes thresholds, denotes a risk state that confers a high chance of developing diabetes. Asians, particularly the Southeast Asian population, may have a higher genetic predisposition to diabetes and increased exposure to environmental and social risk factors. Malaysia alone was home to 3.4 million people with diabetes in 2017; the figure is estimated to reach 6.1 million by 2045. Developing strategies for early interventions to treat prediabetes and preventing the development of overt diabetes and subsequent cardiovascular and microvascular complications are therefore important. Methods: An expert panel comprising regional experts was convened in Kuala Lumpur, for a one-day meeting, to develop a document on prediabetes management in Malaysia. The expert panel comprised renowned subject-matter experts and specialists in diabetes and endocrinology, primary-care physicians, as well as academicians with relevant expertise. Results: Fifteen key clinical statements were proposed. The expert panel reached agreements on several important issues related to the management of prediabetes providing recommendations on the screening, diagnosis, lifestyle and pharmacological management of prediabetes. The expert panel also proposed changes in forthcoming clinical practice guidelines and suggested that the government should advocate early screening, detection, and intensive management of prediabetes. Conclusion: This document provides a comprehensive approach to the management of prediabetes in Malaysia in their daily activities and offer help in improving government policies and the decision-making process.

Thyroid crisis is a life-threatening form of thyrotoxicosis characterized by multi-system dysfunction. Therapeutic plasma exchange has been reported to be effective in removing excessive circulating thyroid hormones. We present a 46-year-old female with recently diagnosed Graves’ disease associated with thyrotoxic cardiomyopathy admitted for thyroid crisis complicated by propranolol-induced circulatory collapse, acute kidney injury and ischemic hepatitis. The tachyarrhythmia was refractory to conventional therapy. Initiation of TPE resulted in rapid clinical and biochemical stabilization.
Thyroid Crisiscirculatory collapse ; Shock ; Cardiomyopathies ; Propranolol