Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy

Objective: Endocrine complications characterised patients with b thalassaemia (bT). In particular,
thyroid dysfunction occurs frequently in bT major, but its long-term natural history is poorly
understood.
Design: A total of 72 bT patients were followed for 8 years. The incidence of thyreopathies, defined as
the primary study endpoint, was assessed. The aim of this study was to analyse the prognostic role of
ferritin for thyreopathies in patients with major and intermedia bT. The power of different iron
chelators to treat iron overload and to prevent or reverse thyreopathies was also assessed.
Methods: Patients were treated with chelators with different chelation strategies during the study.
Receiver operating characteristics analysis was employed to calculate the area under the curve for
serum ferritin to find the best cutoff values capable of identifying thyroid dysfunction in thalassaemic
patients. Kaplan–Meier curves were generated to assess incidence of thyreopathy. Adjusted risk
estimates for thyreopathy were calculated using univariate followed by multivariate Cox proportional
hazard regression analysis.
Results: Patients with thyroid dysfunction were characterised by higher ferritin when compared with
patients without thyreopathies (1500 (872–2336) vs 513 (370–698) mg/l; P!0.0001). Patients with
ferritin values above 1800 mg/l experienced a significantly faster evolution to endpoint (log-rank (c2):
7.7; PZ0.005). Ferritin predicted high risk of thyroid dysfunction independently of confounding
factors (hazard ratio: 1.20; P!0.0001). The intensification of chelation therapy led to an amelioration
of thyroid function.
Conclusions: Ferritin represents a prognostic marker for bT patients and a predictive factor for
progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility
of thyroid complications.