The life expectancy of patients with TM has increased due to improved therapeutic options . However various complications such as endocrinopathies, cardiomyopathies, and bone disorders are still obstacles to treatment in these patients [4,5,6]. In the present study, we noted that endocrinopathies appear early in approximately one fourth of TM patients at the age of 12 years or younger. A high serum ferritin level is usually associated with increased endocrinopathies. Combined iron-chelating agents were associated with a decreased prevalence of endocrine disorders when compared with monotherapy.
In the present study, we report that an increased serum ferritin level is associated with increased endocrine disorders in TM patients. A high prevalence of endocrine abnormalities in TM patients associated with increased iron overload was previously reported [3, 5, 10, 20]. However, other reports did not find a significant relationship between endocrine disorders and serum ferritin level [21, 22].. The serum ferritin level could estimate the liver iron concentration in TM . Moreover, Sobhani et al.  found that higher serum ferritin strongly predicted the severity of cardiac and liver iron overload.
In this study, two thirds of the cases had malnutrition. We defined malnutrition according to WHO definition by Z score for BMI if < − 2, which was the most accepted definition worldwide . Our cases’ BMIs were compatible with those reported by Biswas et al. , who studied 328 TM patients, approximately 37.2% of which were between 11 and 12 years of age. They found that 48.2% were malnourished with a mean BMI of 13.9 ± 1.6 kg/m2. TM has a significant impact on the growth process of children, and hence early intervention is needed to reduce the prevalence of malnutrition as good nutrition with adequate vitamin and trace element intake, along with calcium and vitamin D supplementation, side by side with optimal iron chelating therapy .
Early diagnosis and treatment of TM complications are essential to ensure a good quality of life and to reduce early morbidity and mortality. In TM patients with endocrine disorders, sometime early therapy is recommended in the form of thyroxine therapy. An improvement of subclinical hypothyroidism and primary hypothyroidism has been observed after intensive iron chelation therapy . Therefore, from these data, periodic assessment of iron overload and follow-up of endocrine functions beside improved adherence to chelation therapy should be strongly considered in hospitals in which there are no electronic files or routine follow up of these patients, in order to improve their quality of life and life expectancy.
Iron chelation therapy is the only method of iron overload control in transfusion-dependent patients. In the present study, we found that oral deferasirox is not superior to deferoxamine when used as monotherapy. These data not agree with other reports [27, 28] showing that long-term oral deferasirox therapy may decrease the prevalence of endocrinopathies in TM. The main explanation for this may be the short duration of therapy in our study and the different age groups. However, in our study, combined therapy was associated with a decreased incidence of endocrine disorders, similar to data previously reported by Farmaki et al. . Moreover, Ho et al.  found that combined therapy with deferoxamine and oral deferasirox improved clinical outcomes and quality of life in terms of iron chelation in transfusion-dependent patients with TM at a reasonable cost from a healthcare perspective. The TM patients in the present study had poor compliance to iron-chelating medication; this could explain the occurrence of early endocrine disorders. A similar result was previously reported by Sobhani et al. , who found that irregular use of chelating drugs was associated with a higher risk of iron tissue damage, regardless of the type of chelating agent.
In young children and adults, type 2 diabetes develops over a long period of time, often presenting initially as a pre-diabetic state such as impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). Prediabetes raises the short-term absolute risk of type 2 diabetes by 3-to 10-fold, with some populations exhibiting greater risk than others . Furthermore, pre-diabetic states are also at increased risk of cardiovascular disease . Endocrine abnormalities should be monitored carefully, and a thorough endocrine evaluation should be carried out yearly in every patient with TM to detect subclinical endocrinopathies . Early identification and treatment of persons with prediabetes has the potential to reduce or delay the progression to diabetes .
The total prevalence of abnormal glucose homeostasis in the present study was 7.50%, which could be divided into impaired glucose tolerance (IGT), impaired fasting glucose (IFG), and DM of 5 (4.17%), 4 (3.33%), and 0 (00%), respectively. In previous reports, the prevalence of DM was reported to vary between 0.00%  and 26.70% . In a meta-analysis conducted by He LN et al.  including 35 studies, it was revealed that the prevalence of IGT, IFG, and DM in TM were 12.46, 17.21%, and 6.54, respectively, in patients aged from 2 to 28 years. The increased prevalence of abnormal glucose homeostasis in the previous meta-analysis  could be due to the different age groups. The prevalence of abnormal glucose homeostasis in TM was higher compared to that in non-TM children and young adults, which was 8–17 per 100,000 per year in one cohort .
We reported thyroid disorder in the present study at a rate of 9.17%. However, the overall prevalence of hypothyroidism in TM is variable between studies with different age groups; it was (14.6%) in Iran  and 21.6% in Italy . Different results could be due to genetic, geographical, cultural, and economic factors and also due to the quality of blood transfusions and chelators. Our data demonstrated that the prevalence of hypothyroidism (9.17%) increased in TM patients when compared with non-TM children with sufficient dietary iodine, in which only 0.3–0.4% of children had hypothyroidism, and approximately 4.3–8.5% had subclinical hypothyroidism . Moreover, the prevalence of hypoparathyroidism in our study was (6.6%) which is comparable with that in other studies with different age groups. In Saffari et al.  in TM patients with a mean (SD) age 21.26 ± 4.53 years, the prevalence of hypoparathyroidism was 7.79%, and in De Sanctis et al.  in TM patients with the mean age less than 16 years, the prevalence of hypoparathyroidism was 6.9%.
In our study, we tried to detect endocrine disorders in young age children with TM. However, we did not find any relationship between the duration of TM and endocrine disorders. This could be explained by other factor such as serum ferritin level and patient compliance with cheating therapy having a greater role than disease duration. Furthermore, we did not find a relationship between children with and without endocrine disorders in relation to family history of TM, family history of endocrine disorders, splenectomy, gender, or hemoglobin level before transfusion, in agreement with previously published studies [10, 20].
The presented study had some limitations; liver iron concentration determined by noninvasive magnetic resonance imaging relaxation time techniques was used to estimate body iron load and has been shown to predict total body iron stores more accurately than the serum ferritin level in some reports [39,40,41]. In this study, we measured iron overload from the serum ferritin level as liver iron concentration measurement was not available in our unit. We did not perform a follow up for the cases, as the purpose of this cross-sectional study was to take a picture of the prevalence of endocrinopathies and the risk factors associated with them in this population. We selected this age group because older age groups had already been studied extensively. Serial measurements of other endocrine functions such as growth hormone, reproductive hormones, and adrenal hormones in TM patients, needed in further studies.