the Effects of Deferasirox on Iron in Pituitary, Pancreas and Thyroid Glands: An Observational Case-Control Study
Authors: Unal Sule , Bas Munevver , Hazirolan Tuncay , Tuncer A. Murat , Cetin Mualla , Gumruk Fatma 
Published: October 2019

Abstract
In the absence of adequate chelation therapy, cardiomyopathy caused by iron overload is the leading cause of death in patients with β-thalassemia major (BTM). Additionally, more than half of the adult patients with BTM suffer from hypogonadism (HG), osteoporosis, diabetes mellitus (DM) or hypothyroidism. The use of iron chelators is the mainstay of treatment in patients with BTM to ameliorate these complications. In this study, we aimed to compare the chelation effects of deferasirox (DFX) and other iron chelators on iron in heart, liver, in addition to pituitary, pancreas and thyroid glands.
The study included a total of 37 patients with BTM, who were on the same iron chelator for at least 1 year of duration and above 7 years of age. All of the patients were on iron chelation therapies with either monotherapy with DFX (n=29), desferrioxamine (n=4), deferiprone (n=1) or combination therapy of desferrioxamine and deferiprone (n=3). The mean dose of DFX was 30.8 ± 6.3 mg/kg/day (20-40), the mean dose of desferrioxamine 43.1 ± 5.3 mg/kg/day (39-50) and mean dose of deferiprone was 73.26 ± 9.45 mg/kg/day (70-90). All of the patients were compliant to chelation treatment.
Cardiac T2*, hepatic T2*, thyroid T2 and R2, pituitary T2 and R2, pancreas T2* and R2* MRI were ordered twice to the patients in order to measure the accumulation of iron. The median time interval between the two MRI was 6 months (range 6-11 months). The effect of DFX (n=29) on iron measurements in different organs were compared to the effects of other chelators group (OCG) (n=8).
The mean age of patients participating in the study was 20.8 ± 6.3 years (7.1-36.8). Of the study group, 7.1% of the patients had DM, 8.1% had hypothyroidism and 13.5% had HG at enrollment. According to our previous study for the cut-off value determinations for iron accumulation in BTM with comparison to healthy controls (data unpublished), all of the patients in both groups were found to have pituitary iron accumulation at initial MRI. The changes in iron measures in various organs were summarized in Table 1, indicating a decrease in cardiac, pituitary and pancreas iron loading in both drug groups in follow-up MRI’s (p>0.05). On the other hand δ Liver T2* was negative direction indicating a decrease in hepatic iron loading in DFX group, wheras positive in OCG indicating an increase in follow-up, although insignificant (Table 1, p=0.9). In both groups iron loading in thyroid was found to increase in follow-up and there was no difference between drug groups (Table 1).
In conclusion, DFX is as effective as other drugs in chelation of iron from cardiac, hepatic, pituitary, pancreas and thyroid. The increase in iron in thyroid gland during follow-up in both groups may indicate that iron chelation may not be as efficient in thyroid as it is in other organs. Although, all patients had pituitary iron accumulation, only 13.5% were found to have HG, indicating that patients become symptomatic only occur after a threshold of accumulation was achieved. Our study is initiative for the measurements of iron accumulation with MRI in thyroid.
Table 1. δT2* and δR2 change values between first and second MRI assessments Chelation type Mean±SD Median Range p δ Liver T2 * a (ms) Deferasirox -0.06 -8.5-7.20 0.90 Other chelators 0.79 -0.98-4.40 δ Cardiac T2 * b (ms) Deferasirox -3.83±9.5 0.88 Other chelators -3.2±8.82 δ Pituitary T2 b (ms) Deferasirox -0.7±11.3 0.09 Other chelators -1.4±6.4 δ Pituitary R2 a (Hz) Deferasirox 0.10 -6,20-3,10 0.25 Other chelators 0.20 -4,60-1,30 δ Thyroid R2 a (Hz) Deferasirox -1.4 -6,1-12,7 0.06 Other chelators -0.1 -3,80-8,1 δ Thyroid T2 a (ms) Deferasirox 4.8 -59,8-14,6 0.08 Other chelators 0.4 -20,6-20,1 δ Pancreas T2* b (ms) Deferasirox -7.46±21.6 0.99 Other chelators -7.52±9.63 δ Pancreas R2 * b (Hz) Deferasirox 9.24±45.23 0.11 Other chelators 56.4±73.3
SD: Standard Deviation; aNon-parametric variable, median values were provided; bParametric variables, mean±SD were provided.

Disclosures
No relevant conflicts of interest to declare.