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Assessment of the UK Iodine Status


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Assessment of the UK Iodine Status

  1. 1. Assessment of the UK Iodine Status Application to the Clinical Endocrinology Trust A Sub-Committee of the British Thyroid Association Mark Vanderpump (Chair) Peter Smyth John Lazarus Margaret Eggo Jayne Franklyn British Thyroid Foundation Correspondence: Mark Vanderpump MD FRCP Consultant Physician/Honorary Senior Lecturer in Diabetes and Endocrinology Department of Endocrinology Royal Free Hampstead NHS Trust London NW3 2QG Tel: 0207 472 6280 Fax: 0207 472 6487 Email: 1
  2. 2. Introduction The ideal dietary allowance of iodine recommended by World Health Organisation (WHO) is 150μg of iodine per day, which increases to 250μg in pregnancy and 290μg when lactating. Worldwide many people are still deficient in iodine, despite major national and international efforts to increase iodine intake, primarily through the voluntary or mandatory iodisation of salt. The WHO estimates that two billion people, including 285 million school-age children still have iodine deficiency, defined as a urinary iodine excretion of less than 100μg per litre (1,2) (See Figure 1). This has substantial effects on growth and development and is the most common cause of preventable mental impairment worldwide and iodine supplementation pre-pregnancy may prevent this mild retardation in the intellectual development of future infants and children. Even mild iodine deficiency is thought to lead to reductions of 10-15 in the intelligence quotient (IQ) points. International efforts to control iodine deficiency are slowing, and reaching the third of the worldwide population that remains deficient poses major challenges (3). Fig 1 Epidemiological studies have demonstrated that reduced iodine intake during pregnancy leads to goitrogenesis, lower free thyroxine (T4) concentrations and 2
  3. 3. increase serum thyrotrophin (TSH) in pregnant women (4). The main change in thyroid function associated with the pregnant state is the requirement for an increased production of thyroid hormone that depends directly upon the adequate availability of dietary iodine and the underlying integrity of the thyroid. Physiological adaptation can take place when the iodine intake is adequate. When iodine intake is deficient, pregnancy can reveal an underlying iodine restriction. Severe iodine deficiency may be associated with impairment in the psycho-neurological outcome in the progeny because both mother and offspring are exposed to iodine deficiency during gestation (and the postnatal period). Particular attention is therefore required to ensure that pregnant women receive an adequate iodine supply, by administering multivitamin tablets containing iodine supplements, in order to achieve the WHO recommended dietary allowance of 200–250μg iodine/day. As maternal T4 is crucial to fetal nervous system maturation, even modest states of iodine deficiency could be deleterious. Data from the United States (US) and Netherlands suggest that the children of women with hypothyroxinaemia may have psycho-neurological deficits and delayed mental and motor function when compared with controls (5-7). This correlates with the studies in classic areas of iodine deficiency where a range of psychological and neurological deficits in children has been described during the past century, but in many of the mothers it is the maternal hypothyroxinaemia rather than high TSH that is the clear abnormality (8). Mild to moderate iodine deficiency occurs in areas that are not immediately recognised as iodine deficient. The iodine intake may vary markedly within a country because of significant variations in the natural iodine content of food and water. This was demonstrated in Denmark where pregnant women without iodine supplements had a median iodine excretion level of 66μg/g creatinine in Copenhagen and 33μg/g creatinine in East Jutland (9,10). In countries such as the US, which have been previously considered to be iodine sufficient, iodised salt is used in about 70% of households. However, recent data have shown that the median urinary iodine excretion in adults declined from 320μg/L in 1971-74 to 3
  4. 4. 145μg/L in 1988-94, and was more recently measured at 168μg/L in 2001-2002 (11,12). This US survey also showed that as many as 15% of women in childbearing age, and almost 7% of them during a pregnancy, had iodine excretion levels into the range of moderate iodine deficiency, namely below 50μg/L (13). No data are available for the United Kingdom (UK) population according to a recent publication of the International Council for Control of Iodine Deficiency Disorders (ICCIDD) (14) (See Figure 2). Fig 2 Of all the WHO regions, Europe continues to have the lowest coverage of iodised salt and nearly half of all school-age children have inadequate iodine intakes (14). Although the UK had historically been considered to be a country of 4
  5. 5. sufficient iodine intake (15), concern has been previously expressed about the UK iodine status (16). At the 20-year follow-up of the Whickham survey in 1995 (17), the median urinary iodine excretion for a random sample of 101 subjects aged 38 years and over was 102μg/g creatinine (range 44-990), which did not suggest that iodine deficiency was present in the survivors of this cohort. Concern was expressed about the iodine status of UK women following a more recent survey in Middlesbrough (18). In this study of 227 women at 15 weeks gestation and 227 non-pregnant age-matched controls, 3.5% of the pregnant women had evidence of iodine deficiency and 40% were borderline iodine deficient. This has been supported from data reported in a study of pregnant women in Dundee (19) and Wales (20). A recent study of a small sample of 26 women recruited from the University of Surrey found that the median value for urine iodine was 66μg/L and 20% were classified as iodine deficient (21). Thus up to 50% of pregnant women in the UK could be significantly iodine deficient during gestation. A recent study measured the iodine content in 36 different salt preparations from nine major national supermarkets in Cardiff (22). Iodine concentrations varied from undetectable in 32 samples to trace quantities in two. Only two samples contained meaningful concentrations of iodine (20mg/Kg) related to the prevention of iodine deficiency. A similar pattern of iodine deficiency has been seen in Ireland, with iodine intake being particularly low in the summer months (23). Aim of Study Data on the current iodine status of the UK is therefore lacking and a systematic assessment of the iodine status of the current UK population is now required. The aim of this study is to obtain data to allow the evaluation of the current iodine status of the UK population. This study will focus on young female subjects aged 14-15 years who are pre-pregnancy as they are the most susceptible group to the adverse effects of iodine deficiency as alterations of thyroid function in these 5
  6. 6. subjects are likely to lead to mild retardation in the intellectual development of future infants and children. This study will strengthen monitoring and evaluation of a future ongoing national programme documenting the UK iodine status and for the prevention and control of possible iodine deficiency in the UK. Methods Urinary iodine excretion is a good marker of the recent dietary intake of iodine over days and is therefore the index of choice for evaluating the degree of iodine deficiency. The World Health Organisation/International Council for the Control of the Iodine Deficiency Disorders/United Nations Children’s Fund (WHO/ICCIDD/UNICEF) recommends that for national, school-based surveys of iodine nutrition, the median urinary iodine from a representative sample of spot urine collections from 1200 children (30 sampling clusters of 40 children per cluster) can be used to classify a population’s iodine status (24). Iodine concentrations in casual urine specimens of young women therefore provide an adequate assessment of a population iodine nutrition and target the at risk group for the effects of iodine nutrition. For epidemiological studies, a population distribution of urinary iodine is required rather than individual levels. Because the frequency distribution is usually skewed towards elevated values, the median is considered instead of the mean as indicating the status of iodine nutrition. Data on the current iodine status in the UK will be sought by prospectively analysing the urinary iodine in 1200 female subjects aged 14-15 from the following 10 centres representative of the UK: Aberdeen Newcastle-upon-Tyne Sheffield Birmingham Dundee Exeter London Cardiff Belfast Glasgow 6
  7. 7. Each centre will aim to recruit a total of 120 subjects (3 sampling clusters of 40 subjects per cluster) in each area. Volunteers from 14-15 year-old females attending secondary schools will be sought. In order to aid recruitment, schools with contacts with members of the British Thyroid Association or British Thyroid Foundation will be selected. In order to exclude seasonal factors the samples will be collected in the summer months (May-June 2009). The investigators have experience in obtaining samples on school children by enlisting the assistance of sympathetic teachers, local medical officer or school nurse and involving them in the study. Motivational tools include involving the study as a school project. A 20ml sample of early morning urine will be obtained for each volunteer. Urinary iodine (UI) will be measured using the ammonium persulphate digestion microplate method (25). Quality control will be assessed under the Centre for Disease Control (CDC, Atlanta, Georgia, USA) EQUIP programme. No assessment of goitre size or thyroid function will be made. Iodine levels in local water supply at each centre will be measured. Information from suppliers of iodine supplementation of milk and percentage of salt sold as iodised will be obtained for each area. Multi-centre ethical approval has been given (REC ref no: 09/H0720/47). Funding An award of £21,700 to cover the full costs of the project was given by the Clinical Endocrinology Trust in December 2008. 1. Consumables, specimen collection and sample analysis: 1600 urine samples analysed for iodine concentration by Dr Peter Smyth in Dublin at £5 per sample (Total £8000). Random samples of drinking water for measurement of iodine concentrations in each cluster area from each centre (n=30). Specimen containers and delivery (Total £1000). 7
  8. 8. 2. Part-time Clinical Study Facilitator Further funding will be required for a part-time Clinical Study Facilitator (Band 5 F/T estimated salary £22-29,000 per annum) to coordinate the study and interact with the nominated clinical lead at each centre for the duration of the study and support the data collection. It is proposed that the Facilitator will work for 3 days per week for the duration of the study, which is expected to last for six months. An extra allocation of £2000 (average cost of travel £200 to each centre) will be required for travel expenses for the Facilitator to travel to each centre together with a budget of £1000 for a subsistence allowance when traveling to include possible overnight stays. Expenses Costs Urine iodine analyses £8000 Specimen containers/delivery £2000 P/T Clinical Study Facilitator £8700 (3 days per week for 6 months) Travel/Subsistence Costs £3000 Total £21,700 8
  9. 9. References 1. de Benoist B, Andersson M, Egil I, et al. Iodine status worldwide: WHO global database on iodine deficiency. Geneva: World Health Organisation, 2004. 2. WHO global database on iodine deficiency. Geneva: World Health Organisation. 3. Zimmerman MB, Jooste PL and Pandav CS. Iodine deficiency disorders. Lancet 2008. August 1. (Epub ahead of print). 4. Glinoer D (2005). Thyroid disease during pregnancy. In "Werner and Ingbar's The Thyroid: A Fundamental and Clinical Text", 9/E. (Ed.LE Braverman and RD Utiger). JB Lippincott-Raven, Philadelphia, pp 1086-1108. 5. Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency and subsequent neuropsychological development of the child. N Engl J Med 1999;341:549–555 6. Pop VJ, de Vries E, van Baar AL, et al. Maternal thyroid peroxidase antibodies during pregnancy: a marker of impaired child development? J Clin Endocrinol Metab 1995;80:3561– 3566. 7. Pop VJ, Brouwers EP, Vader HL, et al. Maternal hypothyroxinaemia during early pregnancy and subsequent child development: a 3-year follow-up study. Clin Endocrinol 2003;59:282–288. 8. Lazarus JH. Epidemiology and prevention of thyroid disease in pregnancy. Thyroid. 2002;12:861-865. 9. NФhr SB, Laurberg P, Borlum K-G, et al. Iodine deficiency in Denmark: regional variations and frequency of individual iodine supplementation. Acta Obstet Gynecol Scand 1993;72:350-353. 10. Pedersen KM, Laurberg P, NФhr S, et al. Iodine in drinking water varies by more than 100- fold in Denmark: importance for iodine content of infant formulas. Eur J Endocrinol 1999;140:400-403. 11. Caldwell KL, Jones R, Hollowell JG, et al. Urinary iodine concentration: United States National Health and Nutrition Examination Survey 2001-2002. Thyroid 2005;15:692-699. 12. Hollowell JG, Staehling NW, Hannon WH, et al. Iodine nutrition in the United States. Trends and public health implications: iodine excretion data from national health and nutrition examination surveys I and III (1971–1974 and 1988–1994), J Clin Endocrinol Metab 1998;83:3401–3408. 13. Hollowell JG, Staehling NW, Flanders WD, et al. Serum TSH, T 4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab 2002;87:489-499. 14. International Council for Control of Iodine Deficiency Disorders. IDD Newsletter Volume 29, No 3, August 2008. 15. Lee SM, Lewis J, Buss DH, et al. Iodine in British foods and diets. Br J Nutr 1994;72:435-446 16. Lazarus JH, Phillips DIW, Parkes AB, at al. Status of iodine nutrition in the United Kingdom. in Iodine Deficiency in Europe - A Continuing Concern. F Delange, JT Dunn and D Glinoer eds. NATO ASI Series, Plenum Press (New York) 1993: 323. 9
  10. 10. 17. Vanderpump MPJ, Tunbridge WMG, French JM, et al. (1995). The incidence of thyroid disorders in the community: A twenty-year follow-up of the Whickham Survey. Clin Endocrinol 1995;43:55-69. 18. Kibridge MS, Hutchison S, Owen CJ, et al. Prevalence of maternal dietary iodine insufficiency in the north easy of England: implications for the fetus. Arch Dis Child Fetal Neonatal. Ed 2004;89:436-439. 19. Lazarus JH, Parkes AB, Smyth PPA, et al. Iodine status in early pregnancy :relation to thyroid function. 13th International Thyroid Congress, Buenos Aires, Argentina. Thyroid Abstracts 2005;15:218. 20. Barnett CA, Visser TJ, Williams F, et al. Inadequate iodine intake of 40% of pregnant women from a region in Scotland. J Endocrinol Invest 2002;25(Suppl):90 21. Bath S, Walter A, Taylor A, et al. Iodine status of UK women of child-bearing age. J Human Nutr Dietetics 2008;21:379-380. 22. Lazarus JH and Smyth PPA. Iodine deficiency in the UK and Ireland. Lancet 2008;372:888 23. Nawoor Z, Burns R, Smith DF, et al. Iodine intake in pregnancy in Ireland - a cause for concern? Ir J Med Sci. 2006;175:21-4 24. World Health Organisation/International Council for the Control of the Iodine Deficiency Disorders/United Nations Children’s Fund (WHO/ICCIDD/UNICEF). Assessment of the iodine deficiency disorders and monitoring their elimination. WHO/NHD/01.1. Geneva: World Health Organisation, 2001. 25. Ohashi T, Yamaki Y, Pandav CS, et al. Simple microplate method for determination of urinary iodine. Clin Chem 2000;46:529-536. 10