Assessment of the UK Iodine Status
Application to the Clinical Endocrinology Trust
A Sub-Committee of the British Thyroid Association
Mark Vanderpump (Chair)
British Thyroid Foundation
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
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).
Epidemiological studies have demonstrated that reduced iodine intake during
pregnancy leads to goitrogenesis, lower free thyroxine (T4) concentrations and
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
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
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).
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
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
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
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
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.
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
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:
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).
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).
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.
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
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–
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.
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
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
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,
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.
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
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
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
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
25. Ohashi T, Yamaki Y, Pandav CS, et al. Simple microplate method for determination of urinary
iodine. Clin Chem 2000;46:529-536.