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

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. Distribution of endemic goiter in China before 1979
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
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
perinatal
mortality
Endemic
cretinism
Deaf
mutism
Fetus
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

7. Strategy for Iodine Supplementation
USI
Safe, feasible and highly cost-effective strategy
Others
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.

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

9. 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. 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.
The primary outcome was the prevalence of cretinism at 4- and 10-yr follow-up
Design
at 10 yrs
1.0
1.1
1.2
0.05
0.1
Reduction of endemic cretinism
at 4 yrs
0.17( )
RR(95%CI)
0.2
0.3
0.4
0.5
0.6
0.27( )
Results
Pharoah POD et al. Lancet. 1971, 13;1(7694):
Pharoah PO, Connolly KJ. Int J Epidemiol 1987, 16:68–73

12. Developmental Quotient Increased after IS
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 Nutr :108–114 13

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

15. Infant Mortality Reduced after IS the infant mortality rate
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. Zimmermann MB, et al. J Clin Endocrinol Metab 2007, 92:437–442
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. Zimmermann MB, et al. J Clin Endocrinol Metab 2007, 92:437–442
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
Author UI
Time
Number
Amount
Main Results
Romano
(1991)
Italy
31–37
μg/L T1
SI N=17
Con N=18
μg iodized
salt
In controls, a 16% increase in TV. Treatment had no effect on maternal TSH
Pedersen (1993)
Denmark 55
G17 to term
SI N=28
Con N=26
200μg KI
Maternal 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
G14 to-term
SI N=36
Con N=36
100μg KI
The treated women had smaller TV, and lower TSH and Tg , compared with controls.
TV: thyroid volume

19. Controlled Studies in Mild-to-Moderate ID
Author UI
Time
Number
Amount
Main Results
Liesenkotteer
(1996)
Germany
53 g/g Cr
G11 to term
SI N=38
Con N=70
300μg KI
Treatment 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

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:

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

22. Prevalence of Thyroid Goiter in China Before and After USI (1995–2005)
Time
SIC
(mg/kg)
UIC
(μg/L)
TGR(%)
palpation
B ultrasound
Rate of qualified iodized salt
1995
16.2
164
20.4 -
39.9
1997
37.0
330
10.9
9.6
81.1
1999
42.3
306
8.8
8.0
88.9
2002
31.4
241
5.8
5.1
2005
30.8
246
5.0
4.0
90.2

23. Changes of Type of Thyroid Cancer after USI
Iodine
deficiency
sufficiency
Undifferentiated thyroid cancer
follicular thyroid cancer
papillary thyroid cancer

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 :293–322

26. between Iodine Intake and Thyroid Diseases
U-Shaped Curve
between Iodine Intake and Thyroid Diseases
Iodine Intake Level
Thyroid Disease
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, 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
Denmark n=523 the elderly
*:compatred with other two areas,P<0.05
#:Compared with area with the lowest UI,P<0.05 *
Prevalence(%)] # * #
Hungary n=346 the elderly
Laurberg：J Clin Endocrinol Meatb, 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: 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
μg/day
P Laurberg, Best Practice & Research Clinical Endocrinology & Metabolism 24 (2010) 13–27

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

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

36. Epidemiologic Studies about Iodine and Thyroid Diseases in China
Date
Subject
Contents
population
1999
IITD-1
3 rural communities with MUI 84μg/L, 243 μg/L and 651 μg/L.
3,761
2004
IITD-2
IITD-1 follow-up ( 5 years)
3,018
2007
IITD-3
2 rural communities with MUI 145 μg/L and 261μg/L
3,813
2010
IITD-4
6 cities with more than adequate iodine intake and 4 cities with adequate iodine intake
15,181
2002
PPT
Screening pregnant women and followed-up for 12 months
610
IITD: iodine-induced thyroid diseases;
PPT: postpartum thyroiditis; 36

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

38. IITD-1, IITD-2 Study Design
Zhangwu
Panshan
Huanghua
Study Design
Three communities with iodine- :
Mild deficiency (84μg/L)
More than adequacy (243μg/L)
Excess (614μg/L)
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: 38

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

40. Subclinical hyperthyroidism
IITD-1, IITD-2
HYPERTHYROIDISM, Incidence
Panshan 103μg/L
Zhangwu 375μg/L
Huanghua 615μg/L
1.36
0.94
1.97
0.81
1.04
0.5 1
1.5 2
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#
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:

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

43. IITD-1, IITD-2 THYROID GOITER, Prevalence Prevalence rat (%) * *
19.5 20 20 15 *
13.6 15
Prevalence rat (%) 10 10 *
5.1 # 5 5
3.7
3.5
2.5
Panshan
Zhangwu
Huanghua
Panshan
Zhangwu
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 Incidence rate(‰/year)10 10
7.5
7.08
7.5
6.9
5.01
Incidence rate(‰/year) *
4.4 * 5 5 *
2.41 #
2.5
2.5
0.85 *
Panshan
Zhangwu
Huanghua
Panshan
Zhangwu
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. Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 943-950
IITD-3
Teng XC, Shan ZY, Teng WP: Euro J Endocrinol, 2011,164: 45

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

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

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

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

50. A survey of iodine status and thyroid diseases in ten cities in China
IITD-4
A survey of iodine status and thyroid
diseases in ten cities in China
National Cooperation Group of IITD-4 Study
Weiping Teng
Lulu Chen
Chao Liu
Binyin Shi
Lixin Shi
Zhongyan Shan
Nanwei Tong
Shu Wang
Jianping Weng
Xiaoping Xing
Jiajun Zhao 50 50

51. IITD-4 Distribution of Samples – 10 Cities Shenyang Beijing Jinan
Guangzhou
Shanghai
Jinan
Nanjing
Beijing
Guiyang
Xi’an
Shenyang
Wuhan
Chengdu 51 51

52. IITD-4 Demographic Characteristics of 10 Cities City n Gender (M：F)
Average of Age
Range of Age
Beijing
1539
1：1.9
47.3±13.4
20-88
Chengdu
1500
1：1.2
45.8±15.2
15-82
Guangzhou
1505
1：1.4
45.0±15.2
18-83
Guiyang
1512
45.2±14.8
20-78
Jinan
1：1.5
45.3±14.9
20-82
Nanjing
1572
44.7±15.4
17-92
Shanghai
45.1±14.9
17-82
Shenyang
1549
45.1±15.1
20-84
Wuhan
17-85
Xi’an
46.1±14.8
20-83
Total
15181
45.5±14.9
15-92 52 52

53. IITD-4 Iodine Nutrition Status in 10 Cities
6 cities with adequate iodine intake
4 cities with more than adequate iodine intake
Excessive
282
241
More than Adequate
228
207
196
184
185
174
169
169
156
Adequate
Deficient
Xi’an
Wuhan
Shenyang
Shanghai
Nanjing
Jinan
Guiyang
Guangzhou
Chengdu
Total
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Beijing
Chengdu
Chengdu
Chengdu
Chengdu
Chengdu
Chengdu
Chengdu
Chengdu
Chengdu
Guiyang
Guiyang
Guiyang
Guiyang
Guiyang
Guiyang
Guiyang
Jinan
Jinan
Jinan
Jinan
Jinan
Jinan
Nanjing
Nanjing
Nanjing
Nanjing
Nanjing
Shanghai
Shanghai
Shanghai
Shanghai
Shenyang
Shenyang
Shenyang
Wuhan
Wuhan
Xi’an
Total
Total
Total
Total
Total
Total
Total
Total
Total
Total
Guangzhou
Guangzhou
Guangzhou
Guangzhou
Guangzhou
Guangzhou
Guangzhou
Guangzhou 53 53

54. IITD-4 HYPERTHYROIDISM - Prevalence * N=15,177 Prevalence (%)
3.2%
Prevalence (%)
P=0.000
1.6%
1.2%
1.0%
Clinical Hyperthyroidism
Subclinical Hyperthyroidism 54

55. IITD-4 HYPOTHYROIDISM - Prevalence * * N=15,181 Prevalence (%)
8.2%
P=0.000
Prevalence (%) *
3.8%
P=0.043
2.1%
0.8%
Overt Hypothyroidism
Subclinical Hypothyroidism 55 55

56. IITD-4 ANTITHYROID ANTIBODIES - Prevalence * * N=15,181 P=0.008
13.4%
12.4%
12.0%
11.0% 56 56

57. IITD-4
GOITER - Prevalence
N=15,181 *
P=0.000
1.4%
4.5% 57 57

58. IITD-4 THYROID NODULE - Prevalence * N=15,181 12.4% P=0.000 9.3% 8.4%
3.4% 58 58

59. Postpartum Thyroiditis59

60. Iodine and Postpartum Thyroiditis
Effect of Iodine Intake on
Post-partum Thyroiditis
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
Guan HX, Li CY, Teng WP J Endocrinol Invest. 2005, 2 : 876

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

62. Iodine and Thyroid Dysfunction during Pregnancy
Thyroid dysfunction during late gestation is associated with excessive iodine intake in pregnant women
Sang Zhongna et al. J Clin Endocrinol Metab 2012，97：E

63. Excessive Iodine Intake Increase Thyroid Dysfunction during late Gestation
Sang Zhongna et al. J Clin Endocrinol Metab 2012，97：E

64. 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 64

65. China Medical University
The First Hospital
of CMU 65