Endocrine Abstracts

Introduction: Thalassaemia syndromes are a group of inherited haemolytic disorders determining chronic anaemia, iron overload and organ damage (through the production of ROS), necessitating of iron chelation therapy. Nowadays, there is scant knowledge on hypercalciuria in thalassaemic Western patients. Therefore, aim of our study was evaluating the prevalence of hypercalciuria and identifying risk factors and clinical consequences associated with its development.

Methods: We enrolled 184 patients with β thalassaemia major (TM) aged ≥18 years old, regularly transfused and chelated, and followed up at the Day Hospital of Thalassemia of Ferrara. We excluded patients with severe renal failure, severe hepatopathy, primary hyperparathyroidism, hypoparathyroidism, genetic renal tubular diseases and neoplastic hypercalcemia. Females were not pregnant or breastfeeding. Hypercalciuria was defined by calciuria ≥ 4 mg/kg/day.

Results: The prevalence of hypercalciuria was 69.3% (females 52.5%, mean age 45±7 years old). Hypercalciuric patients had lower ferritin as compared to normocalciuric patients (663,9±766,9 vs 913,2±1151,89 ng/ml, P<0.05). Deferasirox was used mostly in hypercalciuric group (49.2%) rather than in normocalciuric one (28.6%) (P<0.05). Plasma PTH, phosphate and uricemia were lower (P<0,05) in hypercalciuric as compared to normocalciuric patients (PTH 24,1±10,3 vs. 31,4±16,1 pg/ml; phosphoremia 3,6±0,5 vs. 3,8±0,7 mg/dl; uricemia 4±1,3 vs. 4,4±1,4 mg/dl), whereas phosphaturia/24h was higher (0,9±0,4 vs. 0,6±0,3 g/day, P<0,05) (iron mediated subclinical hypoparathyroidism associated with FGF-23 erythropoietin induced hyperphosphaturia?). Supplementation with oral calcium and cholecalciferol was similar in the two groups. Hypercalciuria was associated with a higher frequency of renal lithiasis, vertebral fractures and use of anti-osteoporotic therapy as compared to patients with normocalciuria. Bilateral renal lithiasis, hydronephrosis and nephrocalcinosis were found only in hypercalciuric patients.

Conclusions: Hypercalciuria is a frequent complication in TM. Deferasirox may cause hypercalciuria (through proximal renal tubulopathy) whereas supplementation with oral calcium/cholecalciferol was not associated with this complication. Our study hypothesize a role of ‘FGF23 erythropoietin induced hyperphosphaturia’ and ‘subclinical hypoparathyroidism’ in the pathogenesis of hypercalciuria. Hypercalciuric TM patients have to be monitored for the development of renal damage and osteoporosis.