Introduction: 3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency and lipoid congenital adrenal hyperplasia (CAH) are rare disorders of steroidogenesis that result in impaired synthesis of all adrenal and gonadal hormones. Affected males typically present with ambiguous genitalia and concurrent mineralocorticoid and glucocorticoid deficiency. Distinguishing between these two conditions is crucial, as their management strategies differ. Case: We report a 24-year-old male, born to non-consanguineous parents, who was clinically diagnosed with 3β-HSD deficiency during infancy. He presented at day 40 of life with ambiguous genitalia, bilateral undescended testes, and generalized hyperpigmentation. His family history was significant for an elder brother with salt-losing CAH. Initial biochemical evaluation confirmed primary adrenal insufficiency and primary hypogonadism. Notably, his steroid precursors, dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxyprogesterone, were suppressed. A karyotype confirmed 46,XY. In the absence of genetic testing at that time, a clinical diagnosis of 3β-HSD deficiency was made, and he was commenced on mineralocorticoid and supraphysiological glucocorticoid replacement. He underwent bilateral orchidopexy and hypospadias repair in childhood. Pubertal induction was required, followed by maintenance testosterone therapy. Upon transitioning to adult care, a review of his biochemical profile, particularly suppressed DHEAS, which is inconsistent with 3β-HSD deficiency, raised the suspicion of a more proximal defect, such as lipoid CAH. Differentiation is imperative, as lipoid CAH requires only physiological glucocorticoid replacement, whereas 3β-HSD deficiency often needs higher doses to suppress adrenocorticotropic hormone and DHEAS. To resolve this diagnostic uncertainty and guide longterm therapy, the patient was referred for genetic studies. Conclusion Differentiating 3β-HSD deficiency from lipoid CAH is important, as both have similar clinical presentation. The absence of elevated steroid precursors, particularly DHEAS, should raise suspicion of a more proximal defect. Given the different aims of glucocorticoid therapy, establishing a precise diagnosis through genetic studies is essential to guide clinical management and minimize the morbidity associated with supraphysiological corticosteroid dosing.
Pheochromocytoma ; Mutation

Introduction: Non-diabetic hypoglycemia in older adults warrants careful evaluation across insulin-mediated and noninsulin-mediated causes. We present a challenging case of insulin autoimmune syndrome (IAS; Hirata’s syndrome). Case: An 85-year-old female presented with severe hypoglycemia (capillary blood glucose [CBG] 1.8 mmol/L) with reduced consciousness, preceded by 2 months of recurrent dizziness relieved by food intake. Appetite and weight were stable. Past medical history included stage 3 chronic kidney disease and osteoporosis, but no diabetes. Medication review revealed a recent 2-week course of traditional supplement, long-term Neurobion®, but no agents with recognized hypoglycemic potential. Physical examination showed a moderately built elderly female with a body mass index of 24.3 kg/m² and no Cushingoid features. Recurrent hypoglycemia (CBG nadir 1.5 mmol/L) occurred in both fasting and postprandial states, fulfilling Whipple’s triad. Baseline investigations showed an estimated glomerular filtration rate of 42 mL/min/1.73 m², AM cortisol of 700 mmol/L, and unremarkable liver and thyroid function tests. During a hypoglycemic episode (CBG 2.3 mmol/L), plasma insulin and C-peptide were inappropriately raised at 203.6 mU/L (reference interval [RI]: 3.0– 25.0) and 33 ng/mL (RI: 0.9–7.1), respectively, confirming endogenous hyperinsulinemic hypoglycemia. Polyethylene glycol precipitation showed 21% insulin recovery, raising suspicion for an autoimmune cause. Elevated insulin autoantibodies (175 AU/mL; RI <20) confirmed IAS. Computed tomography of the abdomen and endoscopic ultrasound excluded a pancreatic neuro-endocrine tumor. Nutritional management comprising frequent low glycemic index feeds and uncooked cornstarch was commenced. Diazoxide 100 mg TDS caused fluid overload and severe hyponatremia, while hypoglycemia persisted at lower doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia. Prednisolone 30 mg BD improved glycemic stability. Insulin autoantibodies titer remained 175 AU/mL at 2 weeks; reassessment was conducted at 4 weeks with consideration for biologics if persistent. : doses, necessitating discontinuation. Subcutaneous octreotide 100 mg QID was required to control hypoglycemia. Prednisolone 30 mg BD improved glycemic stability. Insulin autoantibodies titer remained 175 AU/mL at 2 weeks; reassessment was conducted at 4 weeks with consideration for biologics if persistent. Conclusion Endogenous hyperinsulinemic hypoglycemia, after excluding insulinoma, should raise suspicion for IAS. Management includes removing triggers, supportive care, and immunomodulatory therapy in severe cases.

People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.