title: Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy.
abstract: OBJECTIVE
  Endocrine complications characterised patients with β thalassaemia (βT). In particular, thyroid dysfunction occurs frequently in βT major, but its long-term natural history is poorly understood.
  
  
  METHODS
  A total of 72 βT 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 βT. 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 (8722336) VS 513 (370698) G/L; P0.0001). PATIENTS WITH FERRITIN VALUES ABOVE 1800G/L EXPERIENCED A SIGNIFICANTLY FASTER EVOLUTION TO ENDPOINT (LOG-RANK ((2)): 7.7; P=0.005). 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 βT patients and a predictive factor for progression to thyroid dysfunction. Intensive chelation therapy allows the prevention and reversibility of thyroid complications.
authors.forename: Valeria
authors.initials: V
authors.lastname: Chirico
authors.forename: Chirico
authors.initials: C
authors.lastname: Valeria
authors.forename: Antonio
authors.initials: A
authors.lastname: Lacquaniti
authors.forename: Lacquaniti
authors.initials: L
authors.lastname: Antonio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Salpietro
authors.forename: Salpietro
authors.initials: S
authors.lastname: Vincenzo
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Luca
authors.forename: Luca
authors.initials: L
authors.lastname: Nicoletta
authors.forename: Valeria
authors.initials: V
authors.lastname: Ferraù
authors.forename: Ferraù
authors.initials: F
authors.lastname: Valeria
authors.forename: Basilia
authors.initials: B
authors.lastname: Piraino
authors.forename: Piraino
authors.initials: P
authors.lastname: Basilia
authors.forename: Luciana
authors.initials: L
authors.lastname: Rigoli
authors.forename: Rigoli
authors.initials: R
authors.lastname: Luciana
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
authors.forename: Salpietro
authors.initials: S
authors.lastname: Carmelo
authors.forename: Teresa
authors.initials: T
authors.lastname: Arrigo
authors.forename: Arrigo
authors.initials: A
authors.lastname: Teresa
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015913:Chelation Therapy / Q000379:methods*; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005293:Ferritins / Q000097:blood*; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013959:Thyroid Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D016896:Treatment Outcome; D017086:beta-Thalassemia / Q000097:blood* / Q000150:complications* / Q000188:drug therapy
chemical_list: D015415:Biomarkers; D007502:Iron Chelating Agents; D005293:Ferritins