Introduction: Skeletal disease in transfusion-dependent thalassemia is commonly attributed to reduced bone mineral density and managed with anti-resorptive therapy. However, chronic iron overload can induce progressive endocrine siderosis, disrupting anabolic pathways essential for bone homeostasis. This mechanism remains under-recognized and may underlie treatment failure in severe cases. Case: We describe a 34-year-old female with transfusiondependent HbE β-thalassemia, post-splenectomy, receiving regular transfusions and iron chelation, who sustained multiple pathological fractures following a trivial fall, including bilateral supracondylar femur fractures and a distal radius fracture. She had severe systemic iron overload (ferritin 2,621 ng/mL) complicated by hepatic cirrhosis, insulin-dependent diabetes, and hypogonadotropic hypogonadism. Bone mineral density assessment demonstrated severe osteoporosis (hip T-score −5.4) despite prolonged bisphosphonate therapy, with prior vertebral compression fracture. Endocrine evaluation revealed multiaxis dysfunction, including gonadal failure and probable growth hormone deficiency, consistent with pituitary and peripheral endocrine siderosis. Conclusion This case demonstrates that skeletal fragility in transfusiondependent thalassemia reflects an endocrine-driven failure of bone formation rather than isolated loss of bone mineral density. Iron overload–induced endocrine siderosis impairs osteoblast function and suppresses anabolic signaling, leading to profound skeletal vulnerability. The progression of osteoporosis despite anti-resorptive therapy highlights the limitation of conventional approaches and supports reframing thalassemia-associated bone disease as an endocrine disorder. Severe osteoporosis should prompt systematic endocrine evaluation, with early hormonal replacement and consideration of anabolic therapy to prevent catastrophic fractures and long-term disability.
Siderosis ; Thalassemia

Introduction: Autoimmune thyroid disease is frequently associated with other immune-mediated disorders; however, clinically significant pancytopenia is rare. In patients with Graves’ disease receiving antithyroid therapy, leukopenia raises concern for drug-induced agranulocytosis, a rare but potentially life-threatening complication characterized by severe neutropenia requiring immediate drug withdrawal. The coexistence of hemolytic anemia and thrombocytopenia may instead suggest Evans syndrome, defined by autoimmune hemolytic anemia with immune thrombocytopenia, with or without neutropenia. Importantly, uncontrolled thyrotoxicosis itself may cause immunemediated cytopenias, creating a diagnostic challenge. Case: We report a 55-year-old female with thyroid receptor antibody-positive Graves’ disease who presented with jaundice and pancytopenia while receiving carbimazole therapy. Laboratory evaluation demonstrated anemia with reticulocytosis and a positive direct antiglobulin test, thrombocytopenia and leukopenia. Complement testing revealed reduced C3 with normal C4, consistent with immune-mediated hemolysis. Peripheral blood film showed no blast cells or marrow infiltration, and autoimmune screening, including antinuclear antibodies and anti–double stranded DNA, was negative. The coexistence of Coombs-positive hemolysis and thrombocytopenia initially raised suspicion for Evans syndrome, while leukopenia during carbimazole therapy prompted concern for drug-induced agranulocytosis. However, neutropenia was not severe, and the absence of marrow infiltration or systemic autoimmune disease made alternative causes of pancytopenia less likely. Importantly, blood counts progressively improved following the optimization of thyroid control despite continuation of carbimazole at a reduced dose, without the use of immunosuppressive therapy. This clinical course supported the interpretation of thyrotoxicosis-associated immune cytopenia rather than primary Evans syndrome or carbimazole-induced agranulocytosis. Conclusion This case highlights thyrotoxicosis-associated immune cytopenia as an important mimic of Evans syndrome and carbimazole-related hematological toxicity. Recognizing this entity is essential to avoid unnecessary discontinuation of antithyroid therapy or inappropriate immunosuppressive treatment.
Evans Syndrome ; Carbimazole ; Pancytopenia ; Agranulocytosis ; Graves Disease

Introduction: Thyroid stimulating hormone (TSH) suppression following differentiated thyroid carcinoma is widely recommended to reduce recurrence risk. However, this strategy assumes cardiovascular tolerance to supraphysiologic thyroid hormone exposure. In patients with advanced structural heart disease, this assumption may fail, exposing a critical limitation of guideline-directed TSH suppression. Case: We report a 71-year-old male with end-stage renal failure on hemodialysis and severe ischemic cardiomyopathy (ejection fraction 23%) who presented with acute decompensation characterized by dyspnea, rapid atrial fibrillation, and non–ST-elevation myocardial infarction. He had a history of papillary thyroid carcinoma treated with total thyroidectomy and radioactive iodine over 20 years prior and was maintained on levothyroxine 200 mcg daily for TSH suppression. Despite biochemically euthyroid indices (TSH 1.8 mIU/L, free thyroxine 4 17 pmol/L), he developed recurrent arrhythmia with heart failure decompensation. This case highlights a dissociation between biochemical euthyroidism and tissue-level thyrotoxicity in a structurally compromised myocardium. Papillary thyroid carcinoma after definitive therapy typically follows an indolent course with low short-term mortality. In contrast, in severe left ventricular dysfunction, excess thyroid hormone increases adrenergic sensitivity and myocardial oxygen demand, precipitating arrhythmia and ischemia. This risk is amplified in end-stage renal disease, where altered hormone handling renders biochemical indices less reliable. Conclusion Biochemical euthyroidism does not equate to physiological safety. In patients with advanced cardiovascular disease, thyroid hormone therapy should be titrated to cardiovascular tolerance rather than oncologic targets alone, and routine TSH suppression may be inappropriate.
Thyroxine ; Heart Failure ; Thyrotropin

Introduction: Thyrotoxicosis following neck surgery is typically attributed to transient destructive thyroiditis from follicular disruption. In end-stage renal failure (ESRF), however, altered thyroid hormone kinetics, including reduced protein binding, impaired peripheral metabolism, and decreased clearance, can distort biochemical interpretation. This creates a high-risk scenario where laboratory values overestimate tissue thyrotoxicity, predisposing to inappropriate antithyroid therapy. We present a case demonstrating marked clinical–biochemical dissociation, reframing postoperative thyrotoxicosis in ESRF as a disorder of hormone handling rather than hormone overproduction. Case: A 45-year-old female with ESRF on maintenance hemodialysis and tertiary hyperparathyroidism underwent total parathyroidectomy. Preoperative thyroid function was consistently euthyroid. Within 48 hours postoperatively, she developed severe biochemical thyrotoxicosis (thyroidstimulating hormone 0.28 mIU/L, free thyroxine 4 [FT4] 68 pmol/L). Despite this, she remained clinically euthyroid, with stable hemodynamics, absence of adrenergic or neuropsychiatric features, and no evidence of thyroid eye disease. The temporal relationship strongly suggested destructive thyroiditis secondary to surgical manipulation, with passive release of preformed thyroid hormone. In the context of ESRF, impaired hormone clearance and altered binding likely amplified circulating free hormone levels without proportional end-organ effect, resulting in striking clinical–biochemical dissociation. A conservative strategy was adopted. Antithyroid drugs were withheld, given the non-synthetic mechanism of hormone excess, and the patient was managed with close monitoring and symptom-guided beta-blockade. Serial thyroid function demonstrated spontaneous improvement without complications. Conclusion Post-parathyroidectomy thyrotoxicosis in ESRF represents exaggerated biochemical derangement without true tissue toxicity. Management must prioritize physiology over laboratory values, as misclassification risks iatrogenic harm. This case demonstrates that in ESRF, elevated FT4 may not reflect true tissue thyrotoxicity, and reliance on biochemical severity alone can lead to inappropriate antithyroid therapy and iatrogenic harm.
Parathyroidectomy ; Hyperthyroidism ; Thyrotoxicosis