Transfusion-dependent patients typically develop iron-induced cardiomyopathy, liver disease, and endocrine complications. We aimed to estimate the incidence of endocrine disorders in transfusion-dependent thalassemia (TDT) patients during long-term iron-chelation therapy with deferasirox (DFX).We developed a multicentre follow-up study of 426 TDT patients treated with once-daily DFX for a median duration of 8 years, up to 18.5 years. At baseline, 118, 121, and 187 patients had 0, 1, or ≥2 endocrine diseases respectively. 104 additional endocrine diseases were developed during the follow-up. The overall risk of developing a new endocrine complication within 5 years was 9.7% (95%CI=6.3–13.1). Multiple Cox regression analysis identified 3 key predictors: age showed a positive log-linear effect (adjusted HR for 50% increase=1.2, 95%CI=1.1–1.3, P=0.005), the serum concentration of thyrotropin (TSH) showed a positive linear effect (adjusted HR for 1 mIU/L increase=1.3, 95%CI=1.1–1.4, P

Summary Cognitive involvement in beta‐thalassaemia is strikingly controversial and poorly studied in adulthood. This multicentre prospective study investigated 74 adult neurologically‐asymptomatic beta‐thalassaemia patients (mean‐age 34·5 ± 10·3 years; 53 transfusion‐dependent [TDT], 21 non‐transfusion dependent [NTDT]) and 45 healthy volunteers (mean‐age 33·9 ± 10·7 years). Participants underwent testing with Wechsler Adult Intelligence Scale‐Fourth Edition (WAIS‐IV), Brief Psychiatric Rating Scale (BPRS) and multiparametric brain 3T‐magnetic resonance imaging (MRI) for parenchymal, vascular and iron content evaluation. Patients had lower Full‐Scale Intelligence Quotient (FSIQ) than controls (75·5 ± 17·9 vs. 97·4 ± 18·1, P < 0·0001) even after correction for education level. Compared to TDT, NTDT showed a trend of higher FSIQ (P = 0·08) but a similar cognitive profile at WAIS‐subtests. FSIQ correlated with total and indirect bilirubin (P < 0·0001 and P = 0·002, respectively); no correlation was found with splenectomy, intracranial MRI/magnetic resonance‐angiography findings, brain tissue iron content or other disease‐related clinical/laboratory/treatment data. FSIQ did not correlate with BPRS scores, although the latter were higher among patients (28·74 ± 3·1 vs. 27·29 ± 4·8, P = 0·01) mainly because of increased depression and anxiety levels. Occupation rate was higher among controls (84·4% vs. 64·9%, P = 0·004) and correlated with higher FSIQ (P = 0·001) and education level (P = 0·001). In conclusion, Italian adult beta‐thalassaemia patients seem to present a characteristic cognitive profile impairment and an increased rate of psychological disorders with possible profound long‐term socio‐economic consequences.

HighlightsIron overload is a life-threatening condition in beta-thalassemia.Data on brain involvement in systemic iron overload are conflicting.MRI quantification of brain tissue iron content is feasible in a voxel-based approach.No iron tissue excess is evident in beta-thalassemia but in the choroid plexuses.

Lipid abnormalities, including low levels of all fractions of serum lipids, have been repeatedly reported in all phenotypes of beta-thalassemia. Unexpectedly, in more recent studies, the concentration of total cholesterol (TC) and high- and/or low-density lipoprotein cholesterol (HDL-C and LDL-C) has been found in beta-thalassemia intermedia (TI) patients even lower than in thalassemia major, without a clear explanation of pathophysiology of these findings. This lack of information prompted us to evaluate the plasma lipids and lipoproteins pattern in the TI patients followed in our department; the data were compared with those found in hereditary spherocytosis patients. Furthermore, in both groups of patients, the erythroid bone marrow activity was evaluated, utilizing the level of soluble transferrin receptors (sTfR) in the plasma. Both groups of patients showed similar lipid abnormalities (low-TC, HDL-C and LDL-C) and the same increase of sTfR, with significantly lower hemoglobin levels in TI patients. Data analysis of our study shows that the lipid profile in TI patients is not influenced by age, sex, liver injury, hemoglobin or ferritin levels; the higher erythroid bone marrow activity with the enhanced cholesterol consumption could be the dominant mechanism implicated in the lipid abnormalities of TI patients.

Summary Multi‐factorial causes jeopardize brain integrity in β‐thalassaemia. Intracranial parenchymal and vascular changes have been reported among young β‐thalassaemia patients but conventional magnetic resonance imaging (MRI) findings are contradictory making early MRI and magnetic resonance angiography (MRA)/venography monitoring a matter of debate. This study prospectively investigated 75 neurologically asymptomatic β‐thalassaemia patients (mean‐age 35·2 ± 10·7 years; 52/75 transfusion‐dependent; 41/75 splenectomised) using a 3T magnetic resonance scanner; clinical, laboratory and treatment data were also collected. White matter ischaemic‐like abnormalities, intracranial artery stenoses, aneurysms and sinus venous thrombosis were compared between patients and 56 healthy controls (mean‐age 33·9 ± 10·8 years). No patient or control showed silent territorial or lacunar strokes, intracranial artery stenoses or signs of sinus thrombosis. White matter lesions were found both in patients (35/75, 46·7%) and controls (28/56, 50·0%), without differences in terms of number (4·0 ± 10·6 vs. 4·6 ± 9·1, P = 0·63), size and Fazekas’ Score. Intracranial aneurysms did not differ between patients and controls for incidence rate (7/75, 9·3% vs. 5/56, 8·9%), size and site. Vascular and parenchymal abnormality rate did not differ according to treatments or clinical phenotype. According to this study, asymptomatic β‐thalassaemia patients treated according to current guidelines do not seem to carry an increased risk of brain and intracranial vascular changes, thus weakening recommendations for regular brain MRI monitoring.