SUN-758 - Refractory Hypocalcemia in Transfusion-Dependent β-Thalassemia: A Case of Iron Overload–Induced Hypoparathyroidism

Refractory Hypocalcemia in Transfusion-Dependent β-Thalassemia: A Case of Iron Overload–Induced Hypoparathyroidism

Background:
Hypoparathyroidism (HypoPT) affects 10.5–13.5% of transfusion-dependent β-thalassemia patients due to iron overload. Chronic transfusions, lead to oxidative damage and functional impairment of endocrine glands, including the parathyroids. Coexisting endocrinopathies are common, including hypogonadotropic hypogonadism (25.9- 44.5%), diabetes mellitus (6.5-15.9 %), and hypothyroidism (6.3-10.7%). Basal ganglia calcification (BGC) occurs in 54.2% of thalassemia patients with HypoPT, compared to 25.4% in chronic HypoPT from other causes, with some cohorts exceeding 50%.

Results:
A 29-year-old female with transfusion-dependent β-thalassemia, requiring regular transfusions since 3 months of age, was diagnosed with non-surgical HypoPT at age 18-years-old following symptomatic hypocalcemia. The clinical course was complicated by other endocrinopathies, including central hypogonadism and type 2 diabetes. There were no features suggestive of autoimmune polyglandular syndrome or genetic syndromes. Genetic testing is pending. No history of nephrolithiasis or fractures.
Initial management of HypoPT with calcium and alphacalcidol resulted in partial improvement. However, the disease course was marked by recurrent episodes of severe hypocalcemia, requiring emergency care, with documented ionized calcium levels as low as 0.6 mmol/L (NR 1.15-1.35).
Her treatment was optimized: elemental calcium increased to 5 g (three times/day) and alphacalcidol was switched to calcitriol 0.5 mcg (three times/day). Despite this, she continued to experience symptomatic hypocalcemia necessitating IV calcium infusions approximately every two weeks, especially after blood transfusions.
Given persistent symptoms and biochemical instability despite conventional therapy, calcitriol was increased to 1 µg (three times/day), with plans for considering PTH replacement therapy.
Lab investigations in the table demonstrate persistent hypocalcemia, low PTH, hyperphosphatemia, and normal renal function. Vitamin D levels were elevated due to supplementation.
Neuroimaging revealed bilateral BGC, consistent with chronic hypocalcemia.

Conclusion:
HypoPT due to iron overload is a potentially underrecognized cause of non-surgical HypoPT in patients with transfusion-dependent β-thalassemia. The coexistence of multiple endocrinopathies and complications such as BGC highlights the systemic impact of iron toxicity. Early screening, aggressive management of iron overload, and timely consideration of advanced therapies such as PTH replacement in patients with poor response to conventional therapy are essential to reduce morbidity and improve long-term outcomes in this population.

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