Soliman Ashraf T, Yassin Mohamed A, De Sanctis Vincenzo
University of Alexandria, Alexandria, Egypt.
Acta Biomed. 2018 Feb 16;89(2-S):27-32. doi: 10.23750/abm.v89i2-S.7084.
Relatively little is known about endocrine function, bone mineral health, and growth during oral iron chelation therapy in β-thalassemia major patients (TM) on treatment with deferasirox.
To study the frequency of endocrine complications, IGF-1 levels and final adult standing height (FA-Ht) in patients with BTM in two groups of adult patients.
The first group (Group A; 15 patients, 6 females and 9 males) received oral iron chelation therapy (OIC) with deferasirox for 6 years before puberty; the second group (Group B;40 patients) attained the FA-Ht before the use of OIC (iron chelation therapy with deferoxamine (DFO) given subcutaneously, since the age of 2 years). In both groups liver iron concentration was measured using FerriScan ® R2-MRI method. Furthermore, the FA-Ht, bode mass index (BMI), and insulin growth factor-1 (IGF-1) in a selected group of adult patients [9 with normal growth hormone (GH) secretion (GHN) and 8 with GH deficiency (GHD; peak GH response to provocative test with clonidine: < 7 ng/ml), who were on iron chelation therapy with DFO given subcutaneously that was changed to oral deferasirox during the last 5-6 years. These 15 patients were not treated with rhGH.
Adults with BTM who received OIC for 6 years or more before attaining their FA-Ht, had lower liver iron concentration (LIC) assessed by FerriScan® R2-MRI, fasting glucose level (FBG) and liver enzymes (ALT and AST), and a better FA-Ht expressed in standard deviation score (FA-Ht-SDS), and higher IGF-1 SDS versus those who did not receive OIC before attaining FA-Ht. The prevalence of endocrinopathies, including hypothyroidism and hypogonadism were significantly lower in Group A versus Group B. Comparison between the group with normal GHN and those with GHD showed that the FA-Ht-SDS of those with GHD (159.1± 6.42 cm). Ht-SDS = -2.5 ± 0.9) was significantly decreased compared to the group with NGH (Ht = 163.5 ± 5.2 cm, Ht-SDS = -1.74 ± 0.83). The IGF-1-SDS did not differ between the two groups. Neither ferritin level nor IGF-1 concentrations were correlated with the Ht-SDS. The final FA-Ht-SDS correlated significantly with the peak GH secretion (r = 0.788, p = 0.0008). The FA-Ht-SDS were positively related to their mid-parental height (r=0.58, P <0.01).
The use of OIC years before the end of puberty was associated with a significantly lower prevalence of endocrinopathies, improvement of LIC and FA-Ht. The final adult height of patients with BTM and GHD was significantly shorter compared to their pears with NGH. rhGH therapy can be recommended for the treatment of thalassemic children and adolescents with GHD in addition to proper blood transfusion and intensive chelation to improve their final height.
对于接受地拉罗司治疗的重型β地中海贫血（TM）患者，在口服铁螯合治疗期间的内分泌功能、骨矿物质健康和生长情况，我们了解得相对较少。
研究两组成年BTM患者内分泌并发症的发生频率、胰岛素样生长因子-1（IGF-1）水平和最终成人身高（FA-Ht）。
第一组（A组；15例患者，6例女性和9例男性）在青春期前接受地拉罗司口服铁螯合治疗（OIC）6年；第二组（B组；40例患者）在开始OIC治疗（自2岁起皮下注射去铁胺（DFO）进行铁螯合治疗）之前达到FA-Ht。两组均使用FerriScan® R2-MRI方法测量肝脏铁浓度。此外，在一组成年患者中[9例生长激素（GH）分泌正常（GHN）和8例GH缺乏（GHD；可乐定激发试验的GH峰值反应：<7 ng/ml）]测量FA-Ht、体重指数（BMI）和胰岛素样生长因子-1（IGF-1），这些患者接受皮下注射DFO的铁螯合治疗，并在过去5 - 6年改为口服地拉罗司。这15例患者未接受重组人生长激素（rhGH）治疗。
在达到FA-Ht之前接受OIC治疗6年或更长时间的成年BTM患者，通过FerriScan® R2-MRI评估的肝脏铁浓度（LIC）、空腹血糖水平（FBG）和肝酶（ALT和AST）较低，以标准差评分（FA-Ht-SDS）表示的FA-Ht更好，且与在达到FA-Ht之前未接受OIC治疗的患者相比，IGF-1 SDS更高。A组内分泌疾病（包括甲状腺功能减退和性腺功能减退）的患病率明显低于B组。正常GHN组和GHD组之间的比较表明，GHD组的FA-Ht-SDS（身高=159.1±6.42 cm，Ht-SDS=-2.5±0.9）与NGH组（身高=163.5±5.2 cm，Ht-SDS=-1.74±0.83）相比明显降低。两组之间的IGF-1-SDS没有差异。铁蛋白水平和IGF-1浓度均与Ht-SDS无关。最终的FA-Ht-SDS与GH峰值分泌显著相关（r = 0.788，p = 0.0008）。FA-Ht-SDS与其父母平均身高呈正相关（r = 0.58，P <0.01）。
青春期结束前数年使用OIC与内分泌疾病的患病率显著降低、LIC改善和FA-Ht改善相关。与GHN正常的患者相比，BTM和GHD患者的最终成人身高明显更矮。除了适当的输血和强化螯合治疗以改善其最终身高外，建议对患有GHD的地中海贫血儿童和青少年使用rhGH治疗。
