Abstract / Summary
Abstract Background: Thalassemia patients with iron overload often develop a "mixed" hypothyroidism involving both primary thyroid and pituitary failure, but no widely accepted method exists to assess the pituitary component.
Objectives: To evaluate whether TT4RI and TSHI provide insights into early pituitary dysfunction in thalassemia patients, particularly those with subclinical hypothyroidism(SCH) and those with apparently normal thyroid function.
Methods: In this retrospective case-control study, we enrolled 335 thalassemia patients (209 transfusion-dependent [TDT] and 126 non-transfusion-dependent [NTDT]) and 124 healthy controls. TT4RI and TSHI were calculated from thyroid function tests, including hyroid stimulating hormone(TSH), free thyroxine(FT4) and free triiodothyronine(FT3). Elevated TT4RI (>66.52, 95th percentile of controls) and TSHI (>3.71) were compared between SCH and euthyroid patients.
Results: In euthyroid TDT patients, TT4RI and FT3/FT4 ratio were significantly higher than in controls, and this elevation was significant only in those aged ≥10 years. Among SCH patients (n=32, TSH <10 µIU/mL, normal FT4), TT4RI and TSHI were elevated in 81.3% (26/32) and 53.1% (17/32), respectively, versus 3.9% (8/206) and 7.3% (15/206) in euthyroid patients (both P<0.001). No correlation was found with ferritin levels.
Conclusions: TT4RI and TSHI are frequently elevated in thalassemia patients with SCH, suggesting that altered pituitary sensitivity to thyroid hormone feedback may be common in this population. Among euthyroid patients aged ≥10 years, TT4RI was higher in TDT patients than in controls, suggesting pituitary dysfunction may occur before thyroid function is within the normal range.