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Zhongyan SHAN

The Benefit and Concern for Universal Salt Iodination. Zhongyan SHAN. Department of Endocrinology, The First Affiliated Hospital of China Medical University. Content. The reason for USI The benefit about USI The concern about USI.

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Zhongyan SHAN

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  1. The Benefit and Concern for Universal Salt Iodination Zhongyan SHAN Department of Endocrinology, The First Affiliated Hospital of China Medical University

  2. Content • The reason for USI • The benefit about USI • The concern about USI

  3. Distribution of Iodine Deficiency Worldwide IDD Disorders in Developing Countries Iodine deficiency WHO86819 Source: ACC/SCN, 1987

  4. Iodine Status in China Iodine deficiency Distribution of endemic goiter in China before 1979 Ma Tai et al. People's Health Publishing House 1980

  5. Spectrum of IDD across the Life-span Fetus • Abortions • Stillbirths • Congenital • anomalies • Increased • perinatal • mortality • Endemic • cretinism • Deaf • mutism Neonate Child and adolescent Adult • Goiter • hypothyroidism • hyperthyroidism • Impaired mental • function • Retarded • physical • development • Increased • susceptibility of • thyroid gland to • nuclear radiation • Neonatal goiter • Neonatal hypothyroidism • Endemic mental retardation • Increased susceptibility of the thyroid gland to nuclear • radiation • Goiter, with its complications • Hypothyroidism • Impaired mental function • Spontaneous hyperthyroidism in the elderly • Iodine-induced hyperthyroidism Iodine status worldwide WHO Global Database on Iodine Deficiency

  6. Characteristic Features of IDD M. B Zimmermann et al. Lancet 2008; 372: 1251–62. ACC/SCN State-of -the-art series nutrition policy discussion paper No 3.1988

  7. Strategy for Iodine Supplementation

  8. Content • The reason for USI • The benefit about USI • The concern about USI

  9. Benefit in Infant and Childhood After IS

  10. Prevalence of ID Decreased after IS In 2003 In 2007 In 2012 There were 32 countries with ID in total 150 WHO countries. Iodine status worldwide, WHO Global Database on Iodine Deficiency, 2004 M. B Zimmermann et al. Lancet 2008; 372: 1251–62 . Zimmermann M B, and Andersson M Curr Opin Endocrinol Diabetes Obes 2012, 19:382–387

  11. Prevalence of Cretinism Reduced after IS In an severe iodine deficient area in Papua New Guinea Alternate families received saline (control) or iodized oil injection. Design The primary outcome was the prevalence of cretinism at 4- and 10-yr follow-up 0.27(0.12-0.60) Results RR(95%CI) 0.17(0.05-0.58) at 4 yrs at 10 yrs 1.0 1.1 1.2 0.2 0.1 0.05 0.3 0.6 0.5 0.4 Reduction of endemic cretinism Pharoah POD et al. Lancet. 1971, 13;1(7694):308-10. Pharoah PO, Connolly KJ. Int J Epidemiol 1987, 16:68–73

  12. Iodine Supplementation Reduced Cretinism in Severe Iodine Deficient Areas Developmental Quotient Increased after IS Design • In a severe iodine deficient area in western China • Intervention was oral iodized oil at each trimester of pregnancy • Children were divided into • Untreated children: 1–3 yr of age • Treated children born to treated • women were followed for 2 yr. • The main outcomes: • neurological examination • head circumference • Development quotient Cao XY, et al. N Engl J Med 1994,331:1739–1744

  13. Cognition at School Age Improved After IS • A placebo-controlled, double-blind, 6-month intervention trial • Moderately iodine-deficient area in Albania • 10- to 12-yr-old children (n= 310) were randomized • Receive either 400 mg of iodine as oral iodized oil or placebo. • Children were given a serial of seven cognitive and motor tests • Median UI in the treated group was 172μ g/liter at 24 wks • Mean T4 increased approximately 40% compared with placebo Zimmermann MB, et al.Am J Clin Nutr2006 83:108–114

  14. Cognition at School Age Improved After IS 4.7(3.8-5.8) 2.8(1.6-4.0) Rapid target marking RR(95%CI) 2.8(1.9-3.6) Ravens matrices Symbol search 4.5(2.3-6.6) Rapid naming 4.0 4.5 5.0 5.5 6.0 cognitive impairment 0.5 1.0 1.5 2.0 2.5 3.0 3.5 Cognitive Improvement Zimmermann MB, et al.Am J Clin Nutr2006 83:108–114

  15. Infant Mortality Reduced after IS • In three areas of severe iodine deficiency in Xinjiang, China • Potassium iodate for women of childbearing age over a 2- to 4-wk period • Observe neonatal and infant mortality in the following 2–3 yr. the infant mortality rate (/1000 births) The odds of neonatal death were reduced by 65% in iodine treated groups DeLong GR, et al. Lancet, 1997, 350:771–773.

  16. Somatic Growth of Childhood Improved After IS • Aim: to determine whether iodine repletion improves growth in school-age children • Design: Three prospective, double-blind intervention studies in severely, moderately , and mildly iodine-deficient areas. • Intervention: receiving either 400mg of oral iodized oil or placebo for 6 months Zimmermann MB, et al. J Clin Endocrinol Metab 2007, 92:437–442

  17. Somatic Growth of Childhood Improved After IS Height-for-age z-score Weight-for-age z-score Zimmermann MB, et al. J Clin Endocrinol Metab 2007, 92:437–442

  18. Controlled Studies in Mild-to-Moderate ID TV: thyroid volume

  19. Controlled Studies in Mild-to-Moderate ID TV: thyroid volume

  20. Controlled Studies in Mild-to-Moderate ID A Summary • mild-to-moderate iodine deficiency：37-70μg/L • After iodine supplementation of 150~300μg/d • UI concentration increased • Maternal thyroid volume decreased • Neonatal thyroid volume decreased • No effect on maternal FT4, FT3, TSH, and Tg • No long-term follow-up data potential benefit of iodine supplementation in mild-to-moderate iodine deficiency during pregnancy remain unclear Zimmermann M: Thyroid, 2007, 17: 829-835

  21. Benefit about USI in Adulthood

  22. Prevalence of Thyroid Goiter in China Before and After USI (1995–2005)

  23. Changes of Type of Thyroid Cancer after USI

  24. Content • The reason for USI • The benefit about USI • The concern about USI

  25. Recommended Dietary Allowance and Upper Limit of Iodine Intake (μg/d) Recommendation by the U.S. National Academy of Sciences Jean Vanderpas. Annu. Rev. Nutr. 2006. 26:293–322

  26. U-Shaped Curve between Iodine Intake and Thyroid Diseases Thyroid Disease Iodine Intake Level Laurberg P et al: Thyroid 2001,11(5):457

  27. Criteria for Assessing Iodine Nutrition Based on Median of urinary iodine concentrations In school-aged children WHO, UNICEF,ICCIDD, 2007. Geneva: WHO

  28. Optimal Iodine Nutrition and Corresponding Iodine Intake WHO, UNICEF, ICCIDD 2001 A guide for programme managers. WHO publ., Geneva.

  29. Spectrum of Disorders Depends on UIC MUI P LaurbergBest. Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27

  30. Prevalence of Hypothyroidism Increased after USI * *:compared with another area,P<0.05 Prevalence(%)] * MUI Denmarkn=523 the elderly *:compatred with other two areas,P<0.05 #:Compared with area with the lowest UI,P<0.05 * Prevalence(%)] # * # Hungaryn=346 the elderly Laurberg：J ClinEndocrinolMeatb, 1998,83:765. Szabolcs，Clin Endocrinol,97,47:87.

  31. Incidence of Hypothyroidism Increase after USI Aalborg P Laurberg, Best Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27

  32. Incidence of Hyperthyroidism Increased after USI % ppm ppm /100,000 Zimbabwe，1995 Austria，1998 Lancet 1995, 346:1563 Eur J Nucl Med 1998, 25:367

  33. Types of hyperthyroidism in populations with different iodine intake levels Iodine intake level 50-60 μg/day Iodine intake level 250-350 μg/day P Laurberg, Best Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27

  34. Prevalence of AIT and Thyroid Cancer after USI P=0.03 P=0.04 Prevalence of AIT in Poland Prevalence of Thyroid Cancer in Australia Thyroid, 1997, 7: 733-741. Euro J Endocrinol,2002,146:19-26.

  35. Iodine Nutrition of Population in China From 1995 to 2005 330 Excessive 306 241 246 MUI(mcg/L) More than Adequate 165 Adequate Deficient USI Salt iodine was adjusted

  36. Epidemiologic Studies about Iodine and Thyroid Diseases in China IITD: iodine-induced thyroid diseases; PPT: postpartum thyroiditis;

  37. IITD-1, IITD-2 Teng WP, Shan ZY, et al: New Engl J Med 354: 2783-2793

  38. IITD-1, IITD-2 Study Design • Three communities with iodine- : • Mild deficiency (84μg/L) • More than adequacy (243μg/L) • Excess (614μg/L) Zhangwu Panshan Huanghua • Baseline study in 1999 and follow-up in 2004 • To obtain prevalence and incidence of thyroid diseases and an association with iodine intake Teng WP, Shan ZY, et al: New Engl J Med 354: 2783-2793

  39. IITD-1, IITD-2 HYPERTHYROIDISM, Prevalence Zhangwu 375μg/L Huanghua 615μg/L Panshan 103μg/L 4.8 3.9 3.7 4 3.2 2 Prevalence rate[%] 2.4 1.6 1.2 1.1 1.6 0.8 * 0 Overt hyperthyroidism Subclinical hyperthyroidism *:Compared with Panshan and Zhangwu，P<0.05

  40. 1.97 2 1.36 1.36 1.5 1.04 0.94 0.81 1 0.5 0 IITD-1, IITD-2 HYPERTHYROIDISM, Incidence Zhangwu 375μg/L Huanghua 615μg/L Panshan 103μg/L Cumulative incidence[%] Subclinical hyperthyroidism Overt hyperthyroidism

  41. IITD-1, IITD-2 HYPOTHYROIDISM, Prevalence 6.1 # 2.9 2.0 * 0.9 0.9 # * 0.3 *: Compared with Panshan, P<0.05 #: Compared with Panshan and Zhangwu, P<0.05 Teng WP, Shan ZY, et al: New Engl J Med 354: 2783-2793

  42. IITD-1, IITD-2 HYPOTHYROIDISM, Incidence *: Compared with Panshan，P<0.05 2.9 2.6 * * 0.5 0.3 0.2 0.2 Teng WP, Shan ZY, et al: New Engl J Med 354: 2783-2793

  43. IITD-1, IITD-2 THYROID GOITER, Prevalence 19.5 20 20 15 15 * 13.6 Prevalence rat (%) 10 10 * 5.1 # 5 5 3.7 3.5 2.5 0 0 Zhangwu Zhangwu Panshan Panshan Huanghua Huanghua Diffuse goiter Nodular goiter *:Compared with Huanghua,P<0.05 #: Compared with Huanghua and Panshan,P<0.05

  44. IITD-1, IITD-2 THYROID GOITER, Incidence 10 10 7.5 7.08 7.5 6.9 5.01 4.4 Incidence rate(‰/year) * * 5 5 * 2.41 # 2.5 2.5 0.85 * 0 0 Zhangwu Panshan Zhangwu Panshan Huanghua Huanghua Diffuse goiter Nodular goiter *:Compared with Huanghua,P<0.05 #: Compared with Huanghua and Zhangwu,P<0.05 *:Compared with Zhangwu,P<0.05

  45. IITD-3 Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950

  46. IITD-3 Compare difference of thyroid diseases between adequate iodine intake and more than adequate iodine intake • Study Design • Two communities with iodine- : • Adequate (145μg/L) • More than adequate (261μg/L) • A cross-sectional study in 2007 Rongxing Chengshan Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950

  47. IITD-3 Characteristics of Two Communities Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950

  48. IITD-3 HYPOTHYROIDISM prevalence # # * #: Compared with Chengshan, P<0.01 *: Compared with Chengshan, P<0.05 Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950

  49. IITD-3 ANTI-THYROID ANTIBODIES prevalence * * *: Compared with Chengshan, P<0.05 Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950

  50. IITD-4 A survey of iodine status and thyroid diseases in ten cities in China National Cooperation Group of IITD-4 Study

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