Endocrinopathy in thalassemia patients..

Endocrinopathy in thalassemia patients..

1. Dr.Yassin M Alsaleh ENDOCRINOPATHY IN THALASSEMIA ALLPPT.com _ Free PowerPoint Templates, Diagrams and Charts

2. قال تعالى:

3. Endocrine complications

4. Endocrine complications prevalence Abdelhadi M. Habeb , Endocrinopathies in beta- thalassemia major.Prevalence , risk factors, and age at diagnosis in Northwest Saudi Arabia. Saudi Med J 2013. (82%) Naouel Guirat Dhouib,Growth and Endocrine Function in Tunisian Thalassemia Major Patients.Mediterr J Hematol Infect Dis 2018

5. Endocrine complications Abdelhadi M. Habeb , Endocrinopathies in beta- thalassemia major.Prevalence , risk factors, and age at diagnosis in Northwest Saudi Arabia. Saudi Med J 2013.

6. Endocrine complications The severity of the clinical manifestation and laboratory findings in thalassaemia largely depends on the genotype.

7. Mousa A. Alaithan , A comprehensive review of the prevalence of beta globin gene variations and the co-inheritance of related gene variants in Saudi Arabians with beta- thalassemia . Saudi Med J 2018;

8. Growth failure Thalassaemic children show retardation of growth in the foetal , infantile, the pre-pubertal and the pubertal periods. Prevalence of short stature/growth failure: 30-50% KSA : 20.9% Belma Haliloğlu.Endocrinopathies in Turkish Children with Thalassemia Major. J Pediatr Res 2017.

9. Pathophysiology : Chronic Anaemia . iron overload. free radical toxicity . Chelating toxicity zinc deficiency, delayed puberty. hypothyroidism liver impirment . defect in (GH-IGF-1) axis Psychosocial stress Growth failure

10. Chelating agents: at the growth plate may have deleterious effects on local IGF-1 production and paracrine growth regulation inhibits cell proliferation,protein synthesis and mineral deposition. lowering the activity of alkaline phosphatase Growth failure Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017)

11. Defect in the Growth Hormone-Insulin-like Growth Factor-1 (GH-IGF-1) axis: Approximately 20% -30% of such patients have growth hormone (GH) deficiency. The remaining found to have border line result . relative GH resistance (Low serum IGF-1 and normal GH) Growth failure D A Lubis . Endocrinopathies in thalassemia major patient. Series: Earth and Environmental Science (2018)

12. monitoring: for children between 8 and 10 years . weight and height at six monthly interval. insulin-like growth factor (IGF ), and IGF-binding protein-3. GH stimulation. Growth failure

13. Management: Treatment of anaemia and optimizing chelation therapy. Correction of nutritional deficiencies Treatment of other endocrinopathies . recombinant human GH . The response is poor when compared with that of children with GH deficiency. Growth failure

14. most common endocrine abnormality. 70-80% in some studies and may approach even 100%. KSA (52%) Hypogonadism Sasima Srisukh.Hypogonadism in thalassemia major patients. Journal of Clinical & Translational Endocrinology 5 (2016)

15. Hypogonadism

16. lack, delay, and/or block of pubertal sexual maturation Delayed menarche. Oligomenorrhoea . secondary amennorhoea . attenuated breast size. Hypogonadism Presentation: lack, delay, and/or block of pubertal sexual maturation decreased libido erectile dysfunction. Spermatogenesis is impaired the volume of ejaculate is decreased

17. Management: Tanner staging every 6 months . annual evaluation of LH,FSH testosterone,estradiol . Hypogonadism

18. pubertal induction : Hypogonadism For girls: bone age of >11 years low dose oral estrogen cyclic progestogen For boys: Bone age: >12 years testosterone Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017)

19. low dose sex steroids during adolescence (80% reached pubertal maturation) Gross iron overload in the pituitary, hypothalamus and gonads is progressive even with chelation therapy . also post transplant. Hypogonadism Sasima Srisukh.Hypogonadism in thalassemia major patients. Journal of Clinical & Translational Endocrinology 5 (2016) .

20. Vincenzo De Sanctis . Review and Recommendations on Management of Adult Female Thalassemia Patients with Hypogonadism based on Literature Review and Experience of ICET-A Network Specialists . Mediterr J Hematol Infect Dis 2017 Hypogonadism

21. Diabetes Mellitus and glucose intolerance

22. Diabetes Mellitus and glucose intolerance Prevalence DM: 20-30% 6 % in Saudi Arabia. Prevalence pre-DM : 42% Naouel Guirat Dhouib,Growth and Endocrine Function in Tunisian Thalassemia Major Patients.Mediterr J Hematol Infect Dis 2018

23. Pathophysiology : iron induced pancreas cytotoxicity . (inadequate insulin release) . hyperinsulinaemia and decreased insulin sensitivity. No relationship between serum ferritin and development of diabetes was noted. Diabetes Mellitus and glucose intolerance Prevalence of diabetes, impaired fasting glucose and impaired glucose tolerance in patients with thalassemia major in Iran: A meta-analysis study Caspian J Intern Med 2017; 8(1):1-15 2 Azami M, et al

24. Risk factor: higher age. genotype of the individual. volume of blood transfused per occasion. Splenectomy chronic liver disease. viral hepatic infections like Hepatitis C. Diabetes Mellitus and glucose intolerance Ali Bazi . Diabetes Mellitus in Thalassaemia Major Patients: A Report from the Southeast of Iran. Journal of Clinical and Diagnostic Research. 2017

25. Monitoring: TIF guidelines: ≥ 10 years should undergo annual fasting blood sugar And if indicated oral glucose tolerance test. The HbA1c levels are unsuitable. Fructosamine monthly. Diabetes Mellitus and glucose intolerance

26. Management: intensive iron chelation therapy is associated with an improvement in glucose intolerance DFO and (DFP) Management of DM should be individualised Diabetes Mellitus and glucose intolerance Vincenzo De Sanctis.Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy . Mediterr J Hematol Infect Dis 2016.

27. Diabetes Mellitus and glucose intolerance Vincenzo De Sanctis .The ICET-A Recommendations for the Diagnosis and Management of Disturbances of Glucose Homeostasis in Thalassemia Major Patients . Mediterr J Hematol Infect Dis 2016;

28. Thyroid Disorder

29. prevalence of primary hypothyroidism range from 0 - 18% . Thyroid Disorder Zari Tahannejad Asad.Evaluation of serum levels in T3, T4 and TSH in beta- thalassemic patients referred to th Abuzar hospital in Ahwaz. July 2016.

30. Thyroid Disorder Pathophysiology : Autoimmunity has no role in the pathogenesis. ferritin levels correlate with both TSH and thyroid volume and may predict progression of thyroid disease. Benli AR, Yildiz SS, Cikrikcioglu MA. An evaluation of thyroid autoimmunity in patients with beta thalassemia minor.Pak J Med Sci. 2017.

31. monitoring: annual evaluation of TFT beginning at the age of 10 years Treatment: Subclinical hypothyroidism: Optimize chelation . primary or central hypothyroidism : Levothyroxine . Thyroid Disorder Vincenzo De Sanctis.Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy . Mediterr J Hematol Infect Dis 2016.

32. Hypoparathyroidism The prevalence (10-14%) It has a higher incidence in males Usually evident after 10 years of age principally due to iron overload. Increased bone resorption can suppress the PTH secretion from parathyroid Ali Bazi.Hypothyroidism and Hypoparathyroidism in Thalassemia Major Patients: A Study in Sistan and Baluchestan Province, Iran. Int J Endocrinol Metab . 2018 .

33. Tetany , seizures or cardiac failure . Lab: low serum calcium along with high phosphorous (fasting), low/normal PTH Hypoparathyroidism

34. Management: Serum Ca/PO4/ALP 6 monthly PTH annually Treatment: Vitamin D ,one alpha or calcitriol cacium . Hypoparathyroidism Vincenzo De Sanctis.Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy . Mediterr J Hematol Infect Dis 2016.

35. Osteopenia /Osteoporosis WHO definition: decrease in the bone mineral density and disruption of the bone architecture. overall prevalence of “low” bone mass to be 45-51%. Sadia Sultan, Biochemical Markers of Bone Turnover in Patients with 𝛽- Thalasemia Major: A Single Center Study from Southern Pakistan, Advances in Hematology. Volume 2016,

36. Beta- thalassemia is associated with Chronic anaemia , osteopaenia , cortical thickening, trabecular coarsening and bone deformity Osteopenia /Osteoporosis Adlette Inati , Endocrine and Bone Complications in 𝛽-Thalassemia Intermedia : Current Understanding and Treatment. BioMed Research International. Volume 2015,

37. Risk factors: iron overload chelating agent DFO female gender Hypogonadism . Hypoparathyroidism . Vitamin D deficiency diabetes mellitus. Hypothyroidism. Osteopenia/Osteoporosis Parathyroid hormone in pediatric patients with b- thalassemia major and its relation to bone mineral density; a case control study, Mostafa El- Nashar .The Egyptian Journal of Medical Human Genetics (2017)

38. prevalence (78%). Pathophysiolgy : inadequate dietary intake Inadequate sun exposure. malabsorption . hepatic dysfunctions Vitamin D deficiency/ insufficiency Sadia Sultan, Biochemical Markers of Bone Turnover in Patients with 𝛽- Thalasemia Major: A Single Center Study from Southern Pakistan, Advances in Hematology. Volume 2016,

39. AHSA region Deficient below 20 Insufficient below 30

40. Management: Assessment of BMC : Dual energy X-ray absorptiometry (DXA) A baseline DXA evaluation should be done at 10-12 years for girls and boys annually and every 2 years thereafter. Osteopenia/Osteoporosis Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017)

41. In pediatric patients, BMC or aBMD values of < 2 SD are considered as having low bone mass for age. The diagnosis of osteoporosis in pediatrics is based upon : 1-vertebral fractures alone 2- low bone density and multiple long bone fractures (two or more long bone fractures by age the 10 years 3- three or more long bone fractures before age 19 years) Osteopenia/Osteoporosis

42. Management: Early diagnosis and effective chelation therapy is most effective therapy to slow the progression. Diet and exercise calcium and Vitamin D Bisphosphonates Patients with hypogonadism should be treated with HRT. Adult GHD with GH Osteopenia/Osteoporosis

43. Adrenal insufficiency Histological and imaging studies have shown that iron deposits in the adrenal cortex are mainly confined to the zona glomerulosa . Contradictory data exist regarding the pituitary-adrenal dysfunction

44. Patients usually have low serum cortisol . Those with chronic liver disease may have falsely low serum cortisol levels. Adrenal insufficiency Adlette Inati , Endocrine and Bone Complications in 𝛽- Thalassemia Intermedia : Current Understanding and Treatment. BioMed Research International. Volume 2015 .

45. Adrenal function is assessed every 1-2 years beginning from the age of 9 years A morning cortisol levels (8 a.m.) . ACTH stimulation test . Recommendation: glucocorticoid replacement therapy might be advised only for stressful conditions. Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017) Adrenal insufficiency

46. Protocol every 6 months Height and weight growth every 6 months SMR staging. Delayed/Arrested Puberty Annual Blood Glucose (fasting/post prandial ). OGTT if indicated Blood glucose DM/ preDM Annual/Biennial DEXA BMD Osteoporosis 6 monthly Annual PTH Ca/PO4/ALP Hypoparathyroidism Annual Vitamin 25 (OH)D VIT D deficiency Annual FT4/TSH Hypothyroidism Annual morning cortisol Adrenal insufficiency Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017)

47. prevalence of endocrinal complications of patients with TM tunis North west KSA Oman Indonesia Sri lanka UAE India TIF Iran Italy Cyprus 28 81 30 67 95 382 89 3817 220 1861 435 number 42 52.7 73.3 21 52.7 54.1 40.5 22.9 49 32.5 Hypogonadism 57 20.9 65 57.8 55 30.8 39.3 35 Short Stature 14.8 3.3 41 25 6.5 8.9 3.2 7.7 6.2 5.9 HT/SCH 11.1 10 37.8 10.5 10.1 6.9 7.6 3.6 1.2 hypopara 25 26.7 13.2 10.5 13 6,5 8.7 4.9 9.4 DM/IGT Preeti Singh. Growth and endocrine issues in children with thalassemia.Pediatric Hematology Oncology Journal 2 (2017) (modified)

48. Ziad A. Memish . Marked regional variations in the prevalence of sickle cell disease and b- thalassemia in Saudi Arabia: Findings from the premarital screening and genetic counseling program .Journal of Epidemiology and Global Health (2011) 1, 61– 68

49. Nutrients Fatimah Sharif Modawi ., et al. “ Thalassemia Diagnoses and Management”. EC Microbiology 11.1 (2017)

50. Home messages prevention is better than treatment. early and regular chelation therapy is a mandatory for improving the quality of life and psychological outcome .

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