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10 th AOTA CONGRESS Zhongyan SHAN Department of Endocrinology, The First Affiliated Hospital of China Medical University The Benefit and Concern for Universal.

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Presentation on theme: "10 th AOTA CONGRESS Zhongyan SHAN Department of Endocrinology, The First Affiliated Hospital of China Medical University The Benefit and Concern for Universal."— Presentation transcript:

1 10 th AOTA CONGRESS Zhongyan SHAN Department of Endocrinology, The First Affiliated Hospital of China Medical University The Benefit and Concern for Universal Salt Iodination

2 10 th AOTA CONGRESS The reason for USI The benefit about USI The concern about USI Content

3 10 th AOTA CONGRESS IDD Disorders in Developing Countries WHO86819 Source: ACC/SCN, 1987 Distribution of Iodine Deficiency Worldwide Iodine deficiency

4 10 th AOTA CONGRESS Distribution of endemic goiter in China before 1979 Ma Tai et al. People's Health Publishing House 1980 Iodine Status in China Iodine deficiency

5 10 th AOTA CONGRESS Neonate Neonatal goiter Neonatal hypothyroidism Endemic mental retardation Increased susceptibility of the thyroid gland to nuclear radiation Child and adolescent Goiter hypothyroidism hyperthyroidism Impaired mental function Retarded physical development Increased susceptibility of thyroid gland to nuclear radiation Adult Goiter, with its complications Hypothyroidism Impaired mental function Spontaneous hyperthyroidism in the elderly Iodine-induced hyperthyroidism Abortions Stillbirths Congenital anomalies Increased perinatal mortality Endemic cretinism Deaf mutism Fetus Iodine status worldwide WHO Global Database on Iodine Deficiency Spectrum of IDD across the Life-span

6 10 th AOTA CONGRESS M. B Zimmermann et al. Lancet 2008; 372: 1251–62. ACC/SCN State-of -the-art series nutrition policy discussion paper No Characteristic Features of IDD

7 10 th AOTA CONGRESS Safe, feasible and highly cost- effective strategy USI Iodine supplementation of foods and water for human consumption Iodine medications (notably oral administration of iodized oil) to directly supplement the inhabitants at risk of IDD in endemic areas. Active prophylaxis of domestic animals; use of iodine materials for plants or iodine deficient soils. Others Strategy for Iodine Supplementation

8 10 th AOTA CONGRESS The reason for USI The benefit about USI The concern about USI Content

9 10 th AOTA CONGRESS Benefit in Infant and Childhood After IS in moderate-to-severe iodine deficient area Prevalence of iodine deficiency decreased Prevalence of Cretinism reduced Mean developmental quotient increased Infant mortality reduced Cognition of childhood increased Somatic growth of childhood improved in mild-to-moderate iodine deficient area Potential benefit during pregnancy remain unclear

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

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

12 10 th AOTA CONGRESS Cao XY, et al. N Engl J Med 1994,331:1739–1744 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 Iodine Supplementation Reduced Cretinism in Severe Iodine Deficient Areas Developmental Quotient Increased after IS

13 10 th AOTA CONGRESS 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 Nutr :108–114 Cognition at School Age Improved After IS

14 10 th AOTA CONGRESS Zimmermann MB, et al.Am J Clin Nutr :108– Cognitive Improvement Ravens matrices 4.7 ( ) 2.8 ( ) 3.5 RR(95%CI) Rapid target marking Symbol search 2.8 ( ) Rapid naming 4.5 ( ) cognitive impairment Cognition at School Age Improved After IS

15 10 th AOTA CONGRESS DeLong GR, et al. Lancet, 1997, 350:771–773. 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 Infant Mortality Reduced after IS

16 10 th AOTA CONGRESS 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 Somatic Growth of Childhood Improved After IS

17 10 th AOTA CONGRESS Height-for-age z-scoreWeight-for-age z-score Zimmermann MB, et al. J Clin Endocrinol Metab 2007, 92:437–442 Somatic Growth of Childhood Improved After IS

18 10 th AOTA CONGRESS AuthorUITimeNumberAmountMain Results Romano (1991) Italy 31–37 μg/L T1SI N=17 Con N= μg iodized salt In controls, a 16% increase in TV. Treatment had no effect on maternal TSH Pedersen (1993) Denmark 55 μg/L G17 to term SI N=28 Con N=26 200μg KIMaternal TV increased 16% in the treated group vs. 30% in controls. Maternal Tg and TSH were lower in the treated group. Glinoer (1995) Belgium 36 μg/L G14 to- term SI N=36 Con N=36 100μg KIThe treated women had smaller TV, and lower TSH and Tg, compared with controls. TV: thyroid volume Controlled Studies in Mild-to-Moderate ID

19 10 th AOTA CONGRESS AuthorUITimeNumberAmountMain Results Liesenkotteer (1996) Germany 53 g/g Cr G11 to term SI N=38 Con N=70 300μg KITreatment had no significant effect on maternal TSH, T3, T4, TV, or Tg. Antonangeli (2002) Italy 74g/ g Cr G18– 26 to G29– 33 wk. SI-1 N=32 SI-2 N=35 200μg KI 50μg KI no differences in maternal FT4, FT3, TSH, Tg, or TV between groups. TV: thyroid volume Controlled Studies in Mild-to-Moderate ID

20 10 th AOTA CONGRESS mild-to-moderate iodine deficiency 37-70μg/L After iodine supplementation of 150 ~3 00μg/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 Zimmermann M: Thyroid, 2007, 17: potential benefit of iodine supplementation in mild-to- moderate iodine deficiency during pregnancy remain unclear Controlled Studies in Mild-to-Moderate ID A Summary

21 10 th AOTA CONGRESS In adults, iodine supplementation can change the subtype of thyroid cancer decrease the risk of diffuse goiter Benefit about USI in Adulthood

22 10 th AOTA CONGRESS Time SIC (mg/kg) UIC (μg/L) TGR(%) palpation TGR(%) B ultrasound Rate of qualified iodized salt Prevalence of Thyroid Goiter in China Before and After USI (1995–2005)

23 10 th AOTA CONGRESS Type of Thyroid cancer Iodine deficiency Iodine sufficiency Undifferentiated thyroid cancer follicular thyroid cancer papillary thyroid cancer Changes of Type of Thyroid Cancer after USI

24 10 th AOTA CONGRESS Content The reason for USI The benefit about USI The concern about USI

25 10 th AOTA CONGRESS Recommendation by the U.S. National Academy of Sciences Jean Vanderpas. Annu. Rev. Nutr :293–322 Recommended Dietary Allowance and Upper Limit of Iodine Intake (μg/d)

26 10 th AOTA CONGRESS Laurberg P et al: Thyroid 2001,11(5):457 Iodine Intake Level Thyroid Disease U-Shaped Curve between Iodine Intake and Thyroid Diseases

27 10 th AOTA CONGRESS WHO, UNICEF,ICCIDD, Geneva: WHO Criteria for Assessing Iodine Nutrition Based on Median of urinary iodine concentrations In school-aged children

28 10 th AOTA CONGRESS WHO, UNICEF, ICCIDD 2001 A guide for programme managers. WHO publ., Geneva. Optimal Iodine Nutrition and Corresponding Iodine Intake

29 10 th AOTA CONGRESS P LaurbergBest. Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27 Spectrum of Disorders Depends on UIC MUI

30 10 th AOTA CONGRESS Prevalence(%)] *:compared with another area,P<0.05 Denmark n=523 the elderly MUI Laurberg J Clin Endocrinol Meatb, 1998,83:765. Szabolcs Clin Endocrinol,97,47:87. * * # # *:compatred with other two areas,P<0.05 #:Compared with area with the lowest UI,P<0.05 Hungary n=346 the elderly Prevalence(%)] Prevalence of Hypothyroidism Increased after USI * *

31 10 th AOTA CONGRESS P Laurberg, Best Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27 Incidence of Hypothyroidism Increase after USI Aalborg

32 10 th AOTA CONGRESS ppm /100,000 ppm % Zimbabwe 1995Austria 1998 Lancet 1995, 346:1563 Eur J Nucl Med 1998, 25:367 Incidence of Hyperthyroidism Increased after USI

33 10 th AOTA CONGRESS P Laurberg, Best Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27 Types of hyperthyroidism in populations with different iodine intake levels Iodine intake level μg/day Iodine intake level μg/day

34 10 th AOTA CONGRESS Prevalence of AIT in Poland Prevalence of Thyroid Cancer in Australia Thyroid, 1997, 7: Euro J Endocrinol,2002,146: Prevalence of AIT and Thyroid Cancer after USI P=0.03 P=0.04

35 10 th AOTA CONGRESS From 1995 to 2005 Excessive More than Adequate Adequate Deficient MUI(mcg/L) USISalt iodine was adjusted Iodine Nutrition of Population in China

36 10 th AOTA CONGRESS DateSubject Contentspopulation 1999IITD-13 rural communities with MUI 84μg/L, 243 μg/L and 651 μg/L. 3, IITD-2IITD-1 follow-up ( 5 years) 3, IITD-32 rural communities with MUI 145 μg/L and 261μg/L 3, IITD-46 cities with more than adequate iodine intake and 4 cities with adequate iodine intake 15, PPTScreening pregnant women and followed-up for 12 months 610 IITD: iodine-induced thyroid diseases; PPT: postpartum thyroiditis; Epidemiologic Studies about Iodine and Thyroid Diseases in China

37 10 th AOTA CONGRESS Teng WP, Shan ZY, et al: New Engl J Med 354: IITD-1, IITD-2

38 10 th AOTA CONGRESS Zhangwu Panshan Huanghua Three communities with iodine- : –Mild deficiency (84μg/L) –More than adequacy (243μg/L) –Excess (614μg/L) Study Design Baseline study in 1999 and follow-up in 2004 To obtain prevalence and incidence of thyroid diseases and an association with iodine intake IITD-1, IITD-2 Teng WP, Shan ZY, et al: New Engl J Med 354:

39 10 th AOTA CONGRESS Prevalence rate[%] *:Compared with Panshan and Zhangwu P<0.05 * Overt hyperthyroidism Subclinical hyperthyroidism Panshan 103μg/L Zhangwu 375μg/L Huanghua 615μg/L HYPERTHYROIDISM, Prevalence IITD-1, IITD-2

40 10 th AOTA CONGRESS Overt hyperthyroidism Subclinical hyperthyroidism Cumulative incidence[%] HYPERTHYROIDISM, Incidence IITD-1, IITD-2 Panshan 103μg/L Zhangwu 375μg/L Huanghua 615μg/L

41 10 th AOTA CONGRESS * * # # *: Compared with Panshan, P<0.05 #: Compared with Panshan and Zhangwu, P<0.05 HYPOTHYROIDISM, Prevalence IITD-1, IITD-2 Teng WP, Shan ZY, et al: New Engl J Med 354:

42 10 th AOTA CONGRESS *: Compared with Panshan P<0.05 HYPOTHYROIDISM, Incidence * * IITD-1, IITD-2 Teng WP, Shan ZY, et al: New Engl J Med 354:

43 10 th AOTA CONGRESS Panshan Zhangwu Huanghua Prevalence rat (%) Panshan Zhangwu Huanghua Diffuse goiter Nodular goiter # * * *:Compared with Huanghua,P<0.05 #: Compared with Huanghua and Panshan,P<0.05 THYROID GOITER, Prevalence IITD-1, IITD-2

44 10 th AOTA CONGRESS Panshan Zhangwu Huanghua Incidence rate(/year) Panshan Zhangwu Huanghua Diffuse goiter Nodular goiter * * * *:Compared with Zhangwu,P<0.05 *:Compared with Huanghua,P<0.05 #: Compared with Huanghua and Zhangwu,P<0.05 # * THYROID GOITER, Incidence IITD-1, IITD-2

45 10 th AOTA CONGRESS Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: IITD-3

46 10 th AOTA CONGRESS Study Design Two communities with iodine- : –Adequate (145μg/L) –More than adequate (261μg/L) A cross-sectional study in 2007 Compare difference of thyroid diseases between adequate iodine intake and more than adequate iodine intake Rongxing Chengshan Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: IITD-3

47 10 th AOTA CONGRESS Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: Characteristics of Two Communities IITD-3

48 10 th AOTA CONGRESS * # # #: Compared with Chengshan, P<0.01 *: Compared with Chengshan, P<0.05 HYPOTHYROIDISM prevalence Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: IITD-3

49 10 th AOTA CONGRESS ANTI-THYROID ANTIBODIES prevalence * *: Compared with Chengshan, P<0.05 * Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: IITD-3

50 10 th AOTA CONGRESS National Cooperation Group of IITD-4 Study Weiping TengLulu ChenChao Liu Binyin ShiLixin ShiZhongyan Shan Nanwei TongShu WangJianping Weng Xiaoping XingJiajun Zhao A survey of iodine status and thyroid diseases in ten cities in China IITD-4

51 10 th AOTA CONGRESS Distribution of Samples – 10 Cities Chengdu Guangzhou Shanghai Jinan Nanjing Beijing Guiyang Xian Shenyang Wuhan IITD-4

52 10 th AOTA CONGRESS Cityn Gender (M F) Average of AgeRange of Age Beijing ± Chengdu ± Guangzhou ± Guiyang ± Jinan ± Nanjing ± Shanghai ± Shenyang ± Wuhan ± Xian ± Total ± Demographic Characteristics of 10 Cities IITD-4

53 10 th AOTA CONGRESS Excessive Iodine Nutrition Status in 10 Cities More than Adequate Adequate Deficient Total BeijingChengdu Guangzhou GuiyangJinanNanjingShanghai Shenyang XianWuhan Total BeijingChengdu Total Beijing Guangzhou Chengdu Total BeijingGuiyang Guangzhou Chengdu Total BeijingJinanGuiyang Guangzhou Chengdu Total BeijingNanjingJinanGuiyang Guangzhou Chengdu Total BeijingShanghaiNanjingJinanGuiyang Guangzhou Chengdu Total Beijing Shenyang ShanghaiNanjingJinanGuiyang Guangzhou Chengdu Total BeijingWuhan Shenyang ShanghaiNanjingJinanGuiyang Guangzhou Chengdu Total Beijing XianWuhan Shenyang ShanghaiNanjingJinanGuiyang Guangzhou Chengdu Total Beijing 6 cities with adequate iodine intake 4 cities with more than adequate iodine intake IITD-4

54 10 th AOTA CONGRESS * P= % 3.2% 1.2% 1.0% N=15,177 HYPERTHYROIDISM - Prevalence IITD-4 Prevalence (%) Clinical HyperthyroidismSubclinical Hyperthyroidism

55 10 th AOTA CONGRESS * P= % 3.8% 0.8% 2.1% * P=0.043 N=15,181 Subclinical Hypothyroidism Overt Hypothyroidism Prevalence (%) HYPOTHYROIDISM - Prevalence IITD-4

56 10 th AOTA CONGRESS 11.0% 12.4% * P= % 13.4% * P=0.008 N=15,181 ANTITHYROID ANTIBODIES - Prevalence IITD-4

57 10 th AOTA CONGRESS * P= % 4.5% N=15,181 GOITER - Prevalence IITD-4

58 10 th AOTA CONGRESS 12.4% 9.3% * P= % 3.4% * P=0.000 N=15,181 THYROID NODULE - Prevalence IITD-4

59 10 th AOTA CONGRESS Postpartum Thyroiditis

60 10 th AOTA CONGRESS Effect of Iodine Intake on Post-partum Thyroiditis Effect of Iodine Intake on Post-partum Thyroiditis Guan HX, Li CY, Teng WP J Endocrinol Invest. 2005, 2 : 876 Study Design 610 pregnant women enrolled from an iodine- sufficient area The patients with thyroid dysfunction were followed for 12 months after delivery TSH, thyroid hormones and urinary iodine were tested every 3 months Iodine and Postpartum Thyroiditis

61 10 th AOTA CONGRESS * * Guan HX, Li CY, Teng WP J Endocrinol Invest. 2005, 2 : 876 PPT prevalence Iodine and Postpartum Thyroiditis

62 10 th AOTA CONGRESS Sang Zhongna et al. J Clin Endocrinol Metab E Iodine and Thyroid Dysfunction during Pregnancy Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women

63 10 th AOTA CONGRESS Excessive Iodine Intake Increase Thyroid Dysfunction during late Gestation Sang Zhongna et al. J Clin Endocrinol Metab E

64 10 th AOTA CONGRESS Summary USI is a feasible and highly cost-effective strategy Iodine supplementation (IS) can prevent and treat iodine-deficiency disorders Iodine levels that are more than adequate or excessive could increased risk of subclinical hypothyroidism and autoimmune thyroiditis Iodine intake should be maintained at a safe level, MUI between 100 and 200µg/L is a optimal range

65 10 th AOTA CONGRESS China Medical University The First Hospital of CMU


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