H Delshad M D Endocrinologist Research Institute For

H. Delshad M. D Endocrinologist Research Institute For Endocrine Sciences

TSH T 3 T 4 Iodine Thyroid Hormone Synthesis

Iodine nutrition and thyroid function • Iodine is an essential component of thyroid hormone. • In turn, thyroid hormone is critical for neurological development both in utero and in early life. • Sever iodine deficiency results in a spectrum of disorders ……… • Correction of sever iodine deficiency has resulted in better clinical outcomes , worldwide.

• The adverse effects of iodine deficiency in populations (decreased IQ, goiter, hypothyroidism, and hyper-thyroidism) are easily corrected with salt iodisation. • Adequate iodine nutrition in the general population is shown by a median urinary iodine concentration for school-age children (aged 6– 12 years) of 100– 299 μg/L • Adequate iodine nutrition in pregnant women is shown by a median urinary iodine concentration between 150 and 499 μg/L

Iodine nutrition and thyroid function • Mild –moderate iodine deficiency has reemerged in countries previously believed to be iodine sufficient. • Lately, there has been increasing concern that even mild-to-moderate iodine deficiency has adverse clinical outcomes. • Iodine nutrition during pregnancy has become an important public health concern

Author Country pregnant women ( n) Median UIC µg/L Katz PM 2013 Canada Toronto 142 221 ( 142 – 397 ) 29. 6 Lindorfer H 2015 Austria Viena 246 87 86. 2 Granfors M 2015 Sweden 459 98 ( 57 – 148) 100 Fuse Y 2011 Japan 934 219 16. 1 Bath SC 2015 UK 230 56. 8 98 Bath SC 2014 South East UK 100 85. 3 86 Knight BA 2016 South West UK 308 88 ( 54. 3 – 157. 5) 73 Kirkegeard 2016 Denmark 240 Iodine user : 118 ( 79 – 196 ) Non-users: 82 ( 41 – 122) ( IQR ) % UIC < 150 µg/L

Author Country pregnant women ( n) Median UIC µg/L Kasap B 2016 Turkey 135 222 ( 141 – 397 ) 28. 1 Ferreiya SM 2014 Brazil 191 137. 7 (132. 9 – 155. 9 ) 92 Bilek R 2016 Czech Republic 532 82 71. 2 De Zoysa E 2016 Sri Lanka 425 105 (67 – 153) 98 Konrad I 2015 Latvia 696 69. 4 (53. 9 – 92. 6 ) 100 Raverot V 2012 French Lyon 228 81 ( 8 – 832 ) 77 Choyy 2016 Korea 344 427. 3 - ( IQR ) % UIC < 150 µg/L

Mean ±SD age of the cohort : 27 ± 7. 2 years. Mean ±SD gestational age: 20. 7 ± 10. 0 weeks. Min. Max. ﻧﺘﺎﻳﺞ کﻠی UIE (µg /L) ( ) ﻣیﺎﻧﻪ یﺪ ﺍﺩﺭﺍﺭ T 4 (µg/dl) TSH m. IU/L 20 4. 92 0. 01 Preliminary : 400 Results 23. 92 Mean Median 114 87. 3 14. 05 11. 19 2. 20 10. 88 1. 95

Conclusion • Pregnant women living in mild-moderate iodine deficient areas are at particularly high risk of being iodine deficient. Clinical question Iodine supplementation in pregnancyis it time?

How big is the problem? • 32 countries ( 1/3 of the global population) still have inadequate iodine intake. • In Europe: ► 21 countries are iodine deficient in pregnancy ► 10 countries are iodine sufficient ►In 23 countries no data are available

What is the evidence for benefit from iodine supplementation in pregnancy in mild-moderate iodine deficiency? • Avon Longitudinal Study of Parents and Children ( ALSPAC) study in UK • 1040 mother-child pairs • mild-to-moderate iodine deficiency (UIC < 150 µg/l ) in the first trimester of pregnancy : odds of offspring IQ being in the lowest quartile OR = 1. 43; 95%CI 1. 04 -1. 98; P=0. 03

• Hynes et al. from Australia Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9 -year follow-up of the gestational iodine cohort. JCEM 2013

• These studies imply there are potentially substantial benefits from correcting/ preventing even mild iodine deficiency in pregnancy.

• Taylor et al. Impact of iodine supplementation in mild-tomoderate iodine deficiency: systematic review and meta-analysis. Eur J Endo. 2014 Correction of maternal mild-moderate iodine deficiency is likely to improve neurological development of offspring.

Summary of relevant national and societal guidelines Guideline Guidance ATA Australian Department of Health ETA US Teratology Society Endocrine Society All women who are planning to be pregnant or are pregnant or breastfeeding should supplement their diet with a daily oral American Academy of Pediatrics Spanish Endocrine Society World Health Organization UK Department of Health British Thyroid Association supplement of 150 µg of iodine (Endocrine Society : 150 - 200µg ) Pregnant and lactating women should take a supplement containing adequate iodine to achieve a total of 250 µg iodine / day. No specific guidance on iodine intake

Key message • It is probable that, in mild-moderate iodine deficient countries, iodine supplementation during pregnancy and lactation may have substantial obstetric and offspring benefits and is economically advantageous.