1. Presented by : Fawziya Alyafei ped endocrine fellow ped endocrine fellow Department of Pediatrics Endocrinology and Hematology Hamad Medical Center, Qatar

2. Prof Ashraf Soliman Pediatric endocrine senior consultant Dr Lolwa Al-Naimi General pediatric fellow Dr Noora Almarri Pediatric cardiology fellow Dr Aml Sabt Pediatric endocrine specialist Dr Mohamed Yassin Adult Hematology specialist

3. Introduction Thalassemia is one of the most common genetic disorders world wide Thalassemia is one of the most common genetic disorders world wide caused by a reduction of the globin chains leading to chronic hemolytic anemia caused by a reduction of the globin chains leading to chronic hemolytic anemia The mainstay of treatment is blood transfusion to maintain adequate levels of hemoglobin. The mainstay of treatment is blood transfusion to maintain adequate levels of hemoglobin.

4. Introduction Iron overload in β-thalassemia major (TM) patients is a well known complication Iron overload in β-thalassemia major (TM) patients is a well known complication iron overload causes impairment in cellular function and integrity leading to iron-induced injury to varies systems including the endocrine system. iron overload causes impairment in cellular function and integrity leading to iron-induced injury to varies systems including the endocrine system.

5. Introduction Even in carefully managed patients endocrine disturbances still develop including.. Even in carefully managed patients endocrine disturbances still develop including.. 1. Stunted growth, 2. Delayed puberty / hypogonadism, 3. Hypothyroidism 4. Hypoparathyroidism 5. Diabetes mellitus

6. Introduction Hypothyroidism is one of the common endocrine complication (13% and 60%) Hypothyroidism is one of the common endocrine complication (13% and 60%) The symptoms of hypothyroidism are non- specific. But the consequences affect every organ system in the body. The symptoms of hypothyroidism are non- specific. But the consequences affect every organ system in the body. Studies have revealed a wide spectrum of severity varying from primary, subclinical and secondary hypothyroidism Studies have revealed a wide spectrum of severity varying from primary, subclinical and secondary hypothyroidism

9. Aim of the study Determine the prevalence and type of hypothyroidism in all TM patients treated in Hamad Medical Center (HMC) for 12 years Determine the prevalence and type of hypothyroidism in all TM patients treated in Hamad Medical Center (HMC) for 12 years Correlate thyroid function with the degree of iron overload over a 12-year period. Correlate thyroid function with the degree of iron overload over a 12-year period.

10. Patients and Methods 48 patients with BTM (26 F, 22 M) 48 patients with BTM (26 F, 22 M) Age 5-18 years Age 5-18 years Over a 12-year period. Over a 12-year period. On Bld Trx / 3-5 weeks and desferal therapy changed to oral Deferasirox for the past 3 years. On Bld Trx / 3-5 weeks and desferal therapy changed to oral Deferasirox for the past 3 years. No family history of hypothyroidism. No family history of hypothyroidism.

11. Patients and Methods All had complete sexual maturation either spontaneously (n = 44) orthrough sex steroid replacement (n = 4). All had complete sexual maturation either spontaneously (n = 44) orthrough sex steroid replacement (n = 4). All were non-splenectomized All were non-splenectomized Free thyroxine (FT4) and thyrotrophic hormone (TSH)were determined yearly Free thyroxine (FT4) and thyrotrophic hormone (TSH)were determined yearly Serum ferritin concentrations were followed 3 times yearly for 12 years Serum ferritin concentrations were followed 3 times yearly for 12 years

12. Definition of thyroid dysfunction Primary hypothyroidism Primary hypothyroidism FT4 is 5 mIU/ml FT4 is 5 mIU/ml Subclinical hypothyroidism Subclinical hypothyroidism T4 is normal and TSH is > 5 mIU/ml. T4 is normal and TSH is > 5 mIU/ml. Central hypothyroidism Central hypothyroidism FT4 is < 12 pmol/l and TSH is low or normal FT4 is < 12 pmol/l and TSH is low or normal

13. Results

14. Results High prevalence of HT in BTM patients during their second decade of their life (35% at the age of 18 years) High prevalence of HT in BTM patients during their second decade of their life (35% at the age of 18 years) Sixteen of the patients had hypothyroidism after the age of 10 years (94%). Sixteen of the patients had hypothyroidism after the age of 10 years (94%). No significant difference in prevalence in males7/22 (32%) versus females 10/26 (38%) No significant difference in prevalence in males7/22 (32%) versus females 10/26 (38%) None of the patients had high anti thyroperoxidase antibodytiters None of the patients had high anti thyroperoxidase antibodytiters

15. Results

16. Results

17. Results 13 (93.6%)out of the 17 patients with hypothyroidism had normal or low TSH and low FT4 (central hypothyroidism). 13 (93.6%)out of the 17 patients with hypothyroidism had normal or low TSH and low FT4 (central hypothyroidism). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4). Three patients (6.3%) had subclinical hypothyroidism (TSH between 5 uIU/ml and 10 uIU/ml and normal FT4).

18. Results

19. The mean serum ferritin was (2758 ± 592 ug/L) denoted improper iron chelation. The mean serum ferritin was (2758 ± 592 ug/L) denoted improper iron chelation. Ferritin level did not differ between hypothyroid and euthyroid thalassemic patients Ferritin level did not differ between hypothyroid and euthyroid thalassemic patients Results

20. Results

21. Results

22. All patients with TM showed progressive decrease of Ht SDS and BMISDS All patients with TM showed progressive decrease of Ht SDS and BMISDS The HtSDS and BMI of TM patients with hypothyroidism (−1.49 ± 0.55 )did not differ significantly compared to patients with normal thyroid function (−1.38 ± 0.62) The HtSDS and BMI of TM patients with hypothyroidism (−1.49 ± 0.55 )did not differ significantly compared to patients with normal thyroid function (−1.38 ± 0.62) Results

23. Results

24. * Results Results

25. Results Correlation between FT4, TSH and ferritin concentrations AgeTSHT4Ferritin Age 1 TSH -0.271 T4 - 0.59* 0.271 Ferritin 0.33*-0.04 - 0.4* 1

26. Worsening of thyroid function was observed in 35 % of the studied thalassemic patients by the age of 18 years, with a relatively high incidence of defective pituitary thyrotrophic function in these patients. Worsening of thyroid function was observed in 35 % of the studied thalassemic patients by the age of 18 years, with a relatively high incidence of defective pituitary thyrotrophic function in these patients.