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Mild to Moderate Iodine Deficiency

  • Creswell J. EastmanEmail author
  • Mu Li
Chapter

Abstract

Measurement of iodine excretion in urine is the accepted surrogate marker for dietary iodine intake. Results of these measurements are used to classify and report the spectrum of iodine deficiency in a population as mild, moderate or severe, but the evidence supporting these definitions is imprecise and questionable. The current practice of describing a population as being iodine deficient is based on single spot urine iodine excretion measurements, rather than measuring habitual iodine intake. We examine and question current practices of extrapolating spot urine iodine results, obtained in school-age children, to other segments of a population as being representative of iodine deficiency in the population as a whole. We suggest that the time has come for a review of definitions and a revised classification system for iodine deficiency rather than repeating the historical imprecise descriptors of mild, moderate and severe iodine deficiency.

While the crippling, adverse consequences of severe iodine deficiency are indisputable, the frequency and extent of damage – the iodine deficiency disorders (IDD) – caused by the currently accepted definitions of mild to moderate iodine deficiency remains uncertain. Enlargement of the thyroid gland in response to continuing iodine deficiency is a normal physiological adaptation designed to maintain normal secretion of thyroid hormones and prevent deficiency disorders. It only becomes a pathological entity when the body can no longer compensate for inadequate iodine intake and irreversible pathological changes occur. Underpinning our understanding of IDD is the assumption that all of the damage to the central nervous system and other organs occurring in association with iodine deficiency is a consequence of deficient thyroid hormone secretion and action. There is evidence for this assumption in populations suffering from severe iodine deficiency but a paucity of good evidence for any significant effect in mild to moderate iodine deficiency. Of particular interest is the recent findings, in the United Kingdom and Tasmania Australia, of neurocognitive impairment in the offspring of children born to mothers who were documented to have mild iodine deficiency during pregnancy. While we cannot readily explain these findings as no data was collected on maternal and fetal thyroid function, good clinical practice should ensure that iodine intake during pregnancy is optimised while we await the outcome of randomised controlled trials of iodine supplementation during pregnancy.

Keywords

Iodine Neurodevelopment Goiter Thyrotropin Iodine deficiency 

Abbreviations

ADHD

Attention-deficit hyperactivity disorders

ALSPAC

Avon Longitudinal Study of Parents and Children

EAR

Estimated Average Requirement

IDD

Iodine deficiency disorders

IQ

Intelligence quotient

RCT

Randomized clinical trial

RDI

Recommended dietary intake

SAC

School-aged children

TSH

Thyroid stimulating hormone

UIC

Urinary iodine concentration

WHO

World Health Organization

References

  1. 1.
    Hetzel BS. Iodine deficiency disorders (IDD) and their eradication. Lancet. 1983;2:1126–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Hays MT. Estimation of total body iodine content in normal young men. Thyroid. 2001;11:671–5.CrossRefPubMedGoogle Scholar
  3. 3.
    Fisher DA, Oddie TH. Thyroid iodine content and turnover in euthyroid subjects; validity of estimation of thyroid iodine accumulation from short term clearance studies. J Clin Endocrinol Metab. 1969;29:721–7.CrossRefPubMedGoogle Scholar
  4. 4.
    Boyages SC, Halpern JP, Maberly GF, Eastman CJ, Morris JG, Collins JK, et al. A comparative study of neurological and myxedematous endemic cretinism in western China. J Clin Endocrinol Metab. 1988;67:1262–8.CrossRefPubMedGoogle Scholar
  5. 5.
    World Health Organisation. Assessment of iodine deficiency disorders and monitoring their elimination – a guide for programme managers. 3rd ed. Geneva. WHO. 2007.Google Scholar
  6. 6.
    Gaitan E. Goitrogens in food and water. Ann Rev Nutr. 1990;10:21–39.CrossRefGoogle Scholar
  7. 7.
    Brauer VF, Below H, Kramer A, Fuhrer D, Paschke R. The role of thiocyanate in the aetiology of goiter in an industrial metropolitan area. Eur J Endocrinol. 2006;54:229–35.CrossRefGoogle Scholar
  8. 8.
    Institute of Medicine – Food and Nutrition Board. Dietary reference intakes for Vitamins A and K, iodine and other minerals. Washington DC: National Academic Press; 2001.Google Scholar
  9. 9.
    National Health and Medical Research Council, Australia. Nutrient reference values for Australia and New Zealand. 2006. Available from https://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/n35.pdf
  10. 10.
    DeGroot L. Kinetic analysis of iodine metabolism. J Clin Endocrinol Metab. 1966;26:149–73.CrossRefPubMedGoogle Scholar
  11. 11.
    Malvaux P, Beckers C, De Visscher M. Iodine balance in non-goitrous children and in adolescents on a low iodine intake. J Clin Endocrinol Metab. 1969;29:79–84.CrossRefPubMedGoogle Scholar
  12. 12.
    Trumbo P. Evidence to inform the next dietary reference intakes for iodine. Adv Nutr. 2013;4:718–22.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Ristic-Medic D, Novakovic R, Glibetic M, Gurinovic M. EURRECA- estimating iodine requirements for deriving dietary reference values. Crit Rev Food Sci Nutr. 2013;53:1051–63.CrossRefPubMedGoogle Scholar
  14. 14.
    Gunnarsdotir I, Dahl L. Iodine intake in human nutrition; as systematic review. Food Nutr Res. 2012;56:19–31.CrossRefGoogle Scholar
  15. 15.
    Zimmermann MB, Hussein I, Al Ghannami S, El Badawi S, Al Hamad NM, Abbas Hajj B, et al. Estimation of the prevalence of inadequate and excessive iodine intakes in school-age children from the adjusted distribution of urinary iodine concentrations from population surveys. J Nutr. 2016;146:1204–11.CrossRefPubMedGoogle Scholar
  16. 16.
    Mackerras D, Eastman CJ. Estimating the iodine supplementation level to recommend for pregnant and breastfeeding women in Australia. Med J Aust. 2012;197:238–42.CrossRefPubMedGoogle Scholar
  17. 17.
    Li M, Eastman CJ. The changing epidemiology of iodine deficiency. Nat Rev Endocrinol. 2012;8:434–40.CrossRefPubMedGoogle Scholar
  18. 18.
    Mattsson S, Lindstrom S. Diuresis and voiding patterns in healthy schoolchildren. Br J Urol. 1995;76:783–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Als C, Minder C, Willems D, Van Thi HV, Gerber H, Bourdoux P. Quantification of urinary iodine: a need for revised thresholds. Eur J Clin Nutr. 2003;57:1181–8.CrossRefPubMedGoogle Scholar
  20. 20.
    Bourdoux P. Evaluation of the iodine intake; problems of the iodine/creatinine ratio- comparison with iodine excretion and daily fluctuations of iodine concentration. Exp.Clin.Endocrinol Diabetes. 1998;106:S17–20.Google Scholar
  21. 21.
    Li C, Peng S, Zhang X, Wang D, Mao J, Teng X, et al. The urine iodine to creatinine ratio as an optimal index of iodine during pregnancy in an iodine adequate area of China. J Clin Endocrinol Metab. 2016;101:1290–8.Google Scholar
  22. 22.
    Konig F, Andersson M, Hotz K, Aeberli I, Zimmermann M. Ten repeat samples for urinary iodine from spot samples or 24 hour samples are required to reliably estimate individual status in women. J Nutr. 2011;141:2049–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Andersen S, Karmisholt J, Pedersen KM, Laurberg P. Reliability of studies of iodine intake and recommendations for number of samples in groups and individuals. Br J Nutr. 2008;99:813–8.PubMedGoogle Scholar
  24. 24.
    Rasmussen LB, Emmett P, Christiansen E. Day to day and within day variation in urinary iodine excretion. Eur J Clin Nutr. 1999;53:401–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Perrine CG, Cogswell ME, Swanson CA, Sullivan KM, Chen TC, Carriquiry AL, et al. Comparison of population iodine estimates from 24 hour urine and timed spot urine samples. Thyroid. 2014;24:748–57.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Ristic-Medic D, Dullmeijer C, Petrovic-Oggiano G, Popovic T, Arsic A, Glibetic M, et al. Systematic review using meta-analyses to estimate dose-response biomarkers of iodine status in different population groups. Nutr Rev. 2014;214(72):143–61.CrossRefGoogle Scholar
  27. 27.
    Laurberg P, Cerqueira C, Ovesen L, Rasmussen LB, Perrild H, et al. Iodine intake as a determinant of thyroid disorders in populations. Best Pract Res Clin Endocrinol Metab. 2010;24:13–27.CrossRefPubMedGoogle Scholar
  28. 28.
    Rasmussen LB, Schomburg L, Kohrle J, Pedersen IB, Hollenbach B, Hog A, Ovesen L, Perrild H, Lauerberg P. Selenium status, thyroid volume and multiple nodule formation in an area of mild iodine deficiency. Eur J Endocrinol. 2011;164:585–90.CrossRefPubMedGoogle Scholar
  29. 29.
    Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol. 2014;10:136–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Halpern JP, Boyages SC, Maberly GF, Collins JK, Eastman CJ, Morris JG. The neurology of endemic cretinism. Brain. 1991;114:825–41.CrossRefPubMedGoogle Scholar
  31. 31.
    Boyages SC, Halpern JP, Maberly GF, Eastman CJ, Morris JG, Collins JK. Iodine deficiency impairs intellectual and neuromotor development in apparently normal persons: a study of rural inhabitants in north-central China. Med J Aust. 1989;150:676–82.PubMedGoogle Scholar
  32. 32.
    Qian M, Wang D, Watkins WE, Gebski V, Yan YQ, Li M, et al. The effects of iodine on intelligence in children: a meta-analysis of studies conducted in China. Asia Pac J Clin Nutr. 2005;14:32–42.PubMedGoogle Scholar
  33. 33.
    Haddow JE, Pallomake GE, Allan WC, Williams JR, Knight GJ, Gagnon J, et al. Maternal thyroid hormone deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549–55.CrossRefPubMedGoogle Scholar
  34. 34.
    Velasco L, Carreira M, Santiago P. Effect of iodine prophylaxis during pregnancy on neurocognitive development of children during the first two years of life. J Clin Endocrinol Metab. 2009;94:3234–41.CrossRefPubMedGoogle Scholar
  35. 35.
    van Mil NH, Tiemeier H, Bongers-Schokking JJ, Ghassabian A, Hofman A, Hooijkaas H, et al. Low urinary iodine excretion during early pregnancy is associated with alterations in executive functioning in children. J Nutr. 2012;142:2167–74.CrossRefPubMedGoogle Scholar
  36. 36.
    Vermiglio F, LoPresti VP, Moleti M, Sidoti M, Tortorello G, Trimarchi F. Attention deficit hyperactivity disorders in the offspring of mothers exposed to mild to moderate iodine deficiency disorders in developed countries. J Clin Endocrinol Metab. 2004;89:6054–60.CrossRefPubMedGoogle Scholar
  37. 37.
    Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr. 2009;89:668S–72S.CrossRefPubMedGoogle Scholar
  38. 38.
    Zhou SJ, Anderson AJ, Gibson RA, Makrides M. Effect of iodine supplementation in pregnancy on child development and other clinical outcomes: a systematic review of randomized controlled trials. Am J Clin Nutr. 2013;98:1241–54.CrossRefPubMedGoogle Scholar
  39. 39.
    Taylor PN, Okosieme OE, Dayan CM, Lazarus JH. Therapy of endocrine disease: impact of iodine supplementation in mild-to-moderate iodine deficiency: a systematic review and meta-analysis. Eur J Endocrinol. 2013;170:R1–15.Google Scholar
  40. 40.
    Bath SC, Steer CD, Golding J, Emmett P, Rayman MP. Effect of inadequate iodine status in UK pregnant women on cognitive outcomes in their children: results from the Avon Longitudinal Study of Parents and Children (ALSPAC). Lancet. 2013;382:331–7.CrossRefPubMedGoogle Scholar
  41. 41.
    Hynes K, Otahal P, Hay I, Burgess JR. Mild iodine deficiency during pregnancy is associated with reduced educational outcomes in the offspring: 9-year follow up of the Gestational Iodine Cohort. J Clin Endocrinol Metab. 2013;98:1954–62.CrossRefPubMedGoogle Scholar
  42. 42.
    Stagnaro Green A, Pearce E. Iodine and pregnancy: a call to action. Lancet. 2013;382:292–3.CrossRefPubMedGoogle Scholar
  43. 43.
    Johner SA, Thamm M, Schmitz R, Remer T. Examination of iodine status in the German population: an example for methodological pitfalls of the current approach of iodine status. Eur J Nutr. 2016;55:1275–82.CrossRefPubMedGoogle Scholar
  44. 44.
    Zimmerman MB, Anderson M. Assessment of Iodine nutrition in populations; past present and future. Nutr Rev. 2012;70:553–70.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Sydney Medical SchoolUniversity of SydneySydneyAustralia
  2. 2.Board Member Iodine Global Network (IGN)Australian Centre for Control of Iodine Deficiency Disorders (ACCIDD)St LeonardsAustralia

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