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.

Introduction: Gender-affirming hormone therapy (GAHT) for transgender women utilizes estrogen and an anti-androgen like cyproterone acetate (CPA) which can both lead to hyperprolactinemia. Although mild prolactin elevations are common, the development of prolactinomas in transgender women on GAHT is rare. Case: A 23-year-old trans-woman on self-purchased estradiol hemihydrate (17β-estradiol) 4 mg and CPA 12.5 mg daily for GAHT presented with galactorrhea. Investigations revealed markedly elevated prolactin at 2,369 mIU/L and elevated estradiol at 848 pmol/L. A pituitary magnetic resonance imaging (MRI) identified a 0.4 × 0.5 cm microprolactinoma. She declined clinical advice to reduce her medication dose and continued on the same treatment. In the subsequent year, her peak prolactin was 1,383 mIU/L, and a repeat MRI showed the microprolactinoma remained stable. She continues to be on close clinical monitoring. Transgender females experience approximately a fourfold higher rate of developing prolactinomas. The patient’s choice to persist with GAHT reflects the challenges in managing gender dysphoria alongside medical complications. A recent paper by BJ Nolan et al. suggests using prolactin levels exceeding 2,000–3,000 mIU/L to guide further investigations including a pituitary MRI to rule out a prolactinoma. In most cases, the serum prolactin levels will return to the normal range with a reduction or discontinuation of the GAHT. Normalization of prolactin levels have been reported after gonadectomy and CPA cessation in transgender females on GAHT, which suggests that CPA usage may be associated with higher risk of hyperprolactinemia compared to estrogen therapy. Conclusion This case highlights that GAHT can lead to development of prolactinomas. Prolactin monitoring and MRI investigations should be reserved for symptomatic patients, and for those with significantly elevated or increasing prolactin levels. While treatment using dopamine agonists have been reported, this case demonstrates that conservative management and close monitoring can be a viable approach for structurally stable microprolactinomas.
Female ; Prolactinoma ; Transgender Persons

Introduction: Hurthle cell adenoma is a rare benign thyroid neoplasm that can only be diagnosed through histopathological examination. Hurthle cell neoplasm typically presents as nonfunctioning cold nodule on thyroid scintigraphy. We report a rare case of Hurthle cell adenoma presenting with thyroid storm, with unusual findings of “cold” within “hot” thyroid nodule on scintigraphy. Case: A 73-year-old male with hypertension, chronic kidney disease, coronary artery disease, and Parkinson’s disease presented to the emergency department with fever and diarrhea. His temperature was 38.4°C, heart rate 106 bpm, and blood pressure 138/75 mmHg, with atrial fibrillation and signs of heart failure. The Burch-Wartofsky score was 50, consistent with thyroid storm. Laboratory tests revealed free thyroxine 4 37.8 pmol/L (NR 11.5–22.7), free thyroxine 3 5.6 pmol/L (NR 3.5–6.5), and thyroid-stimulating hormone <0.01 mIU/L (NR 0.55– 4.78). Thyroid autoantibodies, including anti-thyroid peroxidase, anti-thyroglobulin, and thyroid-stimulating immunoglobulins, were negative (<0.10 IU/L). The thyroid storm was precipitated by invasive Klebsiella syndrome with endophthalmitis and lung and liver abscess. He was treated with Lugol’s iodine, corticosteroid, antibiotics, and carbimazole. Ultrasound thyroid revealed a mixed cystic-solid nodule in the left thyroid lobe, measuring 2.3 × 3.3 × 4.3 cm (TIRADS category 3). Technetium-99m thyroid scintigraphy demonstrated a hyperfunctioning left thyroid nodule with a focal intranodular cold spot measuring 5.0 × 3.7 cm. Fine needle aspiration cytology of the nodule was benign follicular cells. Following stabilization with anti-thyroid treatment, he underwent left hemithyroidectomy. Histopathology examination revealed a Hurthle cell adenoma without capsular or vascular invasion. Postoperatively, he remained clinically euthyroid. Surveillance ultrasound performed 8 months later showed a normal right thyroid lobe, and lifelong surveillance was planned. Conclusion This case illustrates a rare and unusual presentation of thyroid storm caused by a toxic Hurthle cell adenoma containing an intranodular cold spot on scintigraphy. To our knowledge, only one similar case has been reported in the literature, and our case is the first to present with thyroid storm.
Oxyphil Cells ; Thyroid Crisis ; Adenoma

Introduction: Long-term antithyroid drug (LT-ATD) has emerged as a feasible treatment strategy for patients who decline radioactive iodine (RAI) or thyroidectomy for relapsed or refractory Graves’ disease (GD). Benefits include faster achievement of euthyroidism, lower risk of hypothyroidism, a more favorable cardiovascular profile, and avoidance of surgical risks. Although fluctuations in thyroid status may occur despite good compliance, thyroid storm is exceedingly rare in patients on LT-ATD. While there is no specific data on the incidence of thyroid storm in this cohort, surveys suggest an overall low incidence (0.2–0.76 cases per 100,000 annually). We report a patient with stable GD who developed a thyroid storm despite more than 10 years of LT-ATD. Case: A 40-year-old female was diagnosed with GD 11 years earlier during pregnancy. Treatment was stopped at 25 weeks’ gestation, but she relapsed at 7 months postpartum and was started on carbimazole. She declined RAI or surgery following a relapse and remained on carbimazole 5–10 mg daily, with good compliance. She presented with a 1-day history of fever, cough, rhinorrhea, diarrhea, and palpitations. She was compliant with carbimazole 5 mg daily. On presentation, BP was 132/70 mmHg, HR 140 bpm, temperature 38.5°C, and SpO2 98% on air. She was alert without agitation, had a diffuse goiter, mild proptosis, and conjunctival injection, with otherwise normal findings. Electrocardiogram showed sinus tachycardia. Laboratory investigations demonstrated mild transaminitis, leukocytosis, markedly elevated free T4 (>154 pmol/L), suppressed thyroid-stimulating hormone (<0.008 mIU/L), and elevated thyroid-stimulating immunoglobulin (2.25 IU/L, reference <0.55). Thyroid function tests 1 month ago was normal. Her Burch-Wartofsky score was 60, consistent with thyroid storm, likely precipitated by upper respiratory tract infection. She improved with treatment and was discharged with carbimazole 30 mg daily with planned tapering, subsequently agreeing to RAI as definitive treatment. Conclusion Infection may trigger thyroid storm despite good compliance with LT-ATD. Patients should be counselled regarding this risk and advised to seek early medical attention if thyrotoxic symptoms recur.
Antithyroid Agents ; Thyroid Crisis

Introduction: Macro-thyroid-stimulating hormone (macro-TSH) is a rare complex formed by monomeric TSH with anti-TSH autoantibodies. Macromolecules of TSH are not renally excreted due to its large size, leading to elevated TSH measurements without clinical consequences. This rare condition frequently mimics subclinical hypothyroidism, often leading to misdiagnosis and inappropriate levothyroxine therapy. Case: A 17-year-old female with major depressive disorder was biochemically diagnosed with subclinical hypothyroidism (TSH 39.06 mIU/L, free thyroxine 4 12.9 pmol/L, antithyroid peroxidase negative) and commenced on levothyroxine. Over 5 years, her TSH levels heavily fluctuated (0.48–82.59 mIU/L) and remained persistently elevated with high-normal free T4 levels despite treatment adherence. An endocrinology consult was obtained, and clinical evaluation revealed a clinically asymptomatic and euthyroid patient, with no family history of thyroid disease or supplement use, and there was no goiter. Assay interference was excluded by analyzing her thyroid function tests on a different platform, which yielded similar biochemical results. Subsequently, a polyethylene glycol (PEG) precipitation test was performed. Her pre-PEG TSH of 29.24 mIU/L decreased significantly to 2.78 mIU/L post-PEG. This yielded a remarkably low TSH recovery rate of 9.5%, strongly indicating the presence of macroTSH. Levothyroxine was then stopped, and she remained clinically euthyroid. Conclusion While gel filtration chromatography remains the gold standard for diagnosing this condition, PEG precipitation is a more accessible, cost-effective, and reliable screening method in clinical practice. A TSH recovery rate below 20% is considered highly suggestive of macro-TSH. Clinicians should maintain a high index of suspicion for macro-TSH in asymptomatic patients presenting with isolated TSH elevations that do not respond to thyroxine therapy. Prompt recognition prevents misdiagnosis and avoids the potential risks of unnecessary thyroid hormone replacement.
Hypothyroidism ; Thyrotropin

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.