Abstract
Recently introduced chelation regimens that combine deferoxamine (DFO) and deferiprone (DFP) have been shown to have greater efficacy in promoting iron excretion than either chelator alone and have been associated with rapid reduction of the iron load in the heart and liver, and with reversal of cardiac dysfunction. It is unclear whether this combined therapy could be associated with a decline in the severity of iron-induced endocrinopathies. The primary endpoint of the present study was to investigate the effects of this therapy on the thyroid function in thalassemic patients with subclinical hypothyroidism (SH) or normal thyroid function. Starting in January 2001, 42 patients with b-tlalassaemia major, previously maintained on subcutaneous DFO only, were switched to combined treatment with DFO and DFP. Before the initiation of combined therapy 14 patients had overt hypothyroidism and were treated with thyroxin substitution. The thyroid function of the remaining patients with normal fasting levels of both FT4 and FT3 was further assessed with TRH test. TSH was measured at 0, 30, 60 and 90 minutes after IV injection of 200 mcg of TRH. 15 patients with normal TSH responses (7 males, 8 females, age 28.86 ± 2.20 years, mean ± SEM), and 13 patients (6 males, 7 females, age 31.15 ± 1.85 years), who were considered suffering from SH were finally enrolled. Criteria for the diagnosis of SH was an elevated basal TSH concentration (>5 TSH μIU/ml) or an increment of the TSH levels during the test more than 20 μIU/ml from the basal value. Combination therapy markedly decreased ferritin levels (585 ± 457 vs. 2124 ± 456 μg/l, P < 0.001 in SH group and 868 ± 339 vs. 2877 ± 552 μg/l, P < 0.001 in eythyroidal group). At the time of reassessment (June 2006), the levels of TSH were decreased at all times during the second TRH test in patients with SH: Basal TSH: 4.12 ± 0.63 vs. 6.27 ± 1.08, P=0.01. TSH At 30′ mins: 22.13 ± 2.18 vs. 34.06 ± 4.75, P=0.005. TSH At 60′ mins: 15.89 ± 1.13 vs. 25.69 ± 3.72, P=0.002. TSH At 90′ mins: 11.83±1.26 vs. 19.44±3.27, P=0.001. TSH quantitative secretion, calculated as the area under the curve, was also significantly decreased with combined therapy (1380±118) compared with the initial assessment (2178±312, P=0.004), while no change occurred in basal FT4 (1.06 ± 0.04 vs. 1.15 ± 0.08 in 2001, normal range 0.71–1.85 ng/ml) and FT3 levels (1.55± 0.07 vs. 1.59± 0.08 in 2001, normal range 1.45–3.48 pg/ml). Nevertheless, 7 patients with previous SH exhibited normal results in the reassessment. In patients with previous normal thyroid function TSH response to TRH stimulus was significantly improved only at 60′ mins (9.78±0.73 vs. 11.49±1.28, P=0.03). This study showed that the combination of DFO and DFP followed by an intensive iron chelation might be associated with an improvement in thyroid function in the early stages of hypothyroidism.
Nephrotic Syndrome as a Cause of Transient Clinical Hypothyroidism