François Delange,¹ Bruno de Benoist,² Hans Bürgi,¹ & the ICCIDD Working Group³

OBJECTIVE: Urinary iodine concentration is the prime indicator of nutritional iodine status and is used to evaluate population-based iodine supplementation. In 1994, WHO, UNICEF and ICCIDD recommended median urinary iodine concentrations for populations of 100– 200 µg/l, assuming the 100 µg/l threshold would limit concentrations <50 µg/l to £20% of people. Some scientists felt this proportion was unacceptably high and wanted to increase the threshold above 100 µg/l. The study was carried out to determine the frequency distribution of urinary iodine in iodine-replete populations (schoolchildren and adults) and the proportion of concentrations <50 µg/l.
METHODS: A questionnaire on frequency distribution of urinary iodine in iodine-replete populations was circulated to 29 scientific groups.
FINDINGS: Nineteen groups reported data from 48 populations with median urinary iodine concentrations >100 µg/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111–540 (median 201) µg/l for all populations, 100–199 µg/l in 23 (48%) populations and ³200 µg/l in 25 (52%). The frequencies of values <50 µg/l were 0–20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100–199 µg/l and >200 µg/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years.
CONCLUSIONS: The frequency of urinary iodine concentrations <50 µg/l in populations with median urinary iodine concentrations ³100 µg/l has been overestimated. The threshold of 100 µg/l does not need to be increased. In populations, median urinary iodine concentrations of 100–200 µg/l indicate adequate iodine intake and optimal iodine nutrition.

Keywords Iodine/urine/deficiency; Urine/chemistry; Nutritional status; Reference values; Epidemiologic studies; Child; Adult (source: MeSH, NLM).

Mots clés Iode/urine/déficit; Urine/composition chimique; Etat nutritionnel; Valeur référence; Etude analytique (Epidémiologie); Enfant; Adulte (source: MeSH, INSERM).

Palabras clave Yodo/orina/deficiencia; Orina/química; Estado nutricional; Valores de referencia; Estudios epidemiológicos; Niño; Adulto (fuente: DeCS, BIREME).

Introduction

In 1990, 1572 million people suffered from iodine deficiency, which meant it was the leading cause of preventable mental retardation. Universal salt iodization (USI) — a policy in which all salt used in agriculture, food processing, catering and households is iodized — is the agreed strategy for achieving iodine sufficiency (1). The last decade saw enormous efforts and investments towards achieving this goal, which is now within reach, and the achievements are an unprecedented public health success in the field of noncommunicable diseases (2).

The concentration of iodine in the urine (urinary iodine concentration) is the prime indicator of a person's nutritional iodine status; it is the primary variable used to measure the success of iodine supplementation in a population (1). According to current recommendations produced by the World Health Organization (WHO), United Nations Children's Fund (UNICEF) and International Council for Control of Iodine Deficiency Disorders (ICCIDD), median urinary iodine concentrations of 100–199 µg/l in samples from schoolchildren or adults indicate adequate iodine intake and optimal iodine nutrition (Table 1) (3). This recommendation was made on the basis of the assumption that the threshold of 100 µg/l would allow values <50 µg/l (concentrations that indicates persistent, at least moderate iodine deficiency in the population) in no more than 20% of the population. Some participants at a meeting in 1999 convened by WHO to revise the indicators felt that 20% represented an unacceptably high number of people, and the group considered raising the threshold for the median above the current value of 100 µg/l (3).

It appeared, however, that this concern was not scientifically based, because no hard data were available on the frequency of concentrations of urinary iodine <50 µg/l in populations where the median urinary is >100 µg/l. Such iodine-replete populations could be found in areas where iodine deficiency has never existed, because of adequate food habits — such as Japan or coastal populations in Latin America, for example — or in areas previously affected by iodine deficiency disorders (IDD), where programmes of USI have been implemented successfully.

This study aimed to describe the frequency distribution of urinary iodine concentrations in iodine-sufficient populations (schoolchildren and adults). More specifically, we aimed to evaluate in such populations the proportion of people with concentrations of urinary iodine <50 µg/l.

Methods

We sent a questionnaire to 29 groups of scientists around the world who we thought might have access to the appropriate data. The questionnaire asked each investigator to give a detailed description of the iodine-sufficient area that they had investigated:

– possible past history of iodine deficiency and endemic goitre;

– possible programmes of iodine supplementation and present evidence for normal concentrations; or

– normalized iodine nutrition of the population (prevalence of goitre by palpation, by ultrasounds, blood tests, results of neonatal thyroid screening).

The questionnaire also asked for a description of the populations being studied (characteristics such as number of subjects, age and sex), the mean and median urinary iodine concentrations in the population and the frequency of values below the cut-off values of 100, 50 and 20 µg/l, respectively. These cut-off values correspond to degrees of iodine deficiency defined as moderate, mild and severe (1, 3).

Nineteen groups sent replies with adequate data. These groups constitute the ICCIDD Working Group and are coauthors of this study.

We received responses about 48 populations in 17 countries across four continents. The populations covered a total of 55892people, with population sizes varying from 50 to 16660people. Most (64%) participants were schoolchildren aged 6–14 years, 3% were adults, and the last 33% represented samples of the whole population (aged 2–74 years)

In all population groups (and by definition), median urinary iodine concentrations were >100 µg/l. Median urinary iodine concentrations varied from 111 to 540 (mean ± SD 234 ± 104, median 201) µg/l (Fig. 1). The concentration was 100–199 µg/l in 48% of the populations and >200 µg/l in the remaining 52%. In all groups, iodine sufficiency was confirmed by additional data — most often by a normal prevalence of goitre. In some places, iodine deficiency had never existed — for example in Japan, Iceland and coastal Peru. In others, iodine deficiency had been corrected by the implementation of USI for between one year (one survey each in Indonesia and Bulgaria) and almost 60 years (in the United States of America). By definition, the frequency of values in each group <100 µg/l was <50%(mean ± SD 15.6 ± 11.1).

For all groups taken together, the frequency of values <50 µg/l varied from 0 to 20.8 (mean ± SD 4.8 ± 4.6)%. Frequencies were £12% in all but two populations, for which they were 19.7 and 20.8%. These two populations were from the same Chinese province, in which median urinary iodine concentrations were 128 and 137 µg/l, respectively, only one and two years after correction of IDD. The frequency of values <50 µg/l was inversely related to the median urinary iodine (Fig. 2). The frequency was 7.2 ± 5.4% in samples with median concentrations of 100–200 µg/l and only 2.5 ± 1.7% in samples with medians >200 (mean 307) µg/l. In all populations, the frequency of values <20 µg/l varied from 0 to 6 (mean ± SD 1.0 ± 1.5)%.

When the 39 906 schoolchildren in the 48 population samples were considered separately from the adults, the results were very similar to those observed in the total population under investigation. The mean urinary iodine concentration was 297 ± 147 µg/l and the median 240 µg/l. The frequencies of values below 100, 50 and 20 µg/l were 16.2, 4.9 and 1.0, respectively. When the schoolchildren with median urinary iodine concentrations of 100–200 µg/l (26 270 children; median 157 µg/l) were considered separately, the frequency of values <50 µg/l was 7.8%. The latter frequency was only 2.6% in the 13 636 schoolchildren with a median urinary iodine concentration >200 (mean 307) µg/l.

Discussion

The results show that the risk of persistent iodine deficiency in iodine-sufficient populations with median urinary iodine concentrations ³100 µg/l is much lower than the 20% assumed by WHO, UNICEF and ICCIDD in 1994 (1).

The frequency of urinary iodine concentrations <50 µg/l is 2.5% and 2.6% in global populations and schoolchildren, respectively, when the median concentration of urinary iodine is about 300 µg/l. In such conditions, which are reported from many parts of the world after implementation of USI (4), the risk of persistent iodine deficiency is very low. The problem with such iodine concentrations is the increased risk of iodine-induced hyperthyroidism (5–7); this is especially so when they are achieved suddenly in populations previously exposed to long-standing, severe iodine deficiency (8–10).

A series of investigations showed that urinary iodine concentrations vary considerably from day to day and during a single day in one individual (11–13). During successive sampling of the same groups of individuals, problematic values of <50 µg/l were not found every time a sample was taken from one individual. Thus, a single urinary iodine measurement is not representative of an individual's nutritional iodine status. Urinary iodine concentrations are useful, however, when used in cross-sectional, epidemiological surveys in population samples of appropriate size.

The frequency of urinary iodine concentrations <50 µg/l in populations with median urinary iodine concentrations ³100 µg/l is 4.8% — much lower than the value of 20% assumed previously. Moreover, the intra- and inter-day variability of urinary iodine suggests that values below the critical level of 50 µg/l may not be present permanently in one member of a given population.

The critical threshold of 100 µg/l as an indicator of iodine sufficiency does not need to be increased. This study, which used hard data, further supports the statement that, at a population level, a median urinary iodine level between 100 and 200 µg/l indicates adequate iodine intake and optimal iodine nutrition (3).

Acknowledgements

This study was supported by a grant from the Department of Nutrition for Health and Development of WHO, and by ICCIDD. The authors thank all members of the ICCIDD Working Group for their enthusiastic collaboration and Professor Michèle Dramaix, Director, Laboratory of Medical Statistics, School of Public Health, University of Brussels, Brussels, Belgium for her kind contribution to the statistical analysis.

Conflicts of interest: none declared.

Résumé

Détermination de la concentration médiane d'iode urinaire indicative d'un apport d'iode suffisant dans une population

OBJECTIF: La concentration d'iode urinaire est le principal indicateur de l'état nutritionnel en ce qui concerne l'iode et elle est utilisée pour évaluer la supplémentation en iode au niveau d'une population. En 1994, l'OMS, l'UNICEF et l'ICCIDD ont recommandé des concentrations médianes d'iode urinaire de 100-200 µg/l, en admettant que le seuil de 100 µg/l limiterait les concentrations <50 µg/l à £20% de la population. Certains auteurs ont estimé cette proportion beaucoup trop élevée et ont souhaité relever le seuil au-dessus de 100 µg/l. La présente étude avait pour but de déterminer la distribution de fréquence de la concentration d'iode urinaire dans des populations ayant un apport d'iode suffisant (écoliers et adultes) et la proportion de concentrations <50 µg/l.
MÉTHODES: Un questionnaire sur la distribution de fréquence de l'iode urinaire dans des populations ayant un apport d'iode suffisant a été remis à 29 groupes scientifiques.
RÉSULTATS: Dix-neuf groupes ont rapporté des données issues de 48populations ayant des concentrations médianes d'iode urinaire >100 µg/l. L'effectif total de ces populations était de 55 892 personnes, dont 35 661 (64%) écoliers. Les concentrations médianes d'iode urinaire étaient de 111-540 (médiane 201) µg/l dans toutes les populations, de 100-199 µg/l dans 23 (48%) populations et ³200 µg/l dans 25 (52%) populations. La fréquence des valeurs <50 µg/l était globalement de 0-20,8% (moyenne 4,8%); elle était de 7,2% dans les populations où la valeur médiane était de 100-199 µg/l et de 2,5% dans celles où la médiane était >200 µg/l. Elle n'atteignait 20% que dans deux endroits où la supplémentation en iode était appliquée depuis moins de deux ans.
CONCLUSION: La fréquence des concentrations d'iode urinaire <50 µg/l dans les populations où la valeur médiane des concentrations d'iode urinaire est ³100 µg/l a été surestimée. Le seuil de 100 µg/l n'a pas besoin d'être relevé. Des concentrations médianes d'iode urinaire de 100-200 µg/l dans une population indiquent un apport d'iode suffisant et un bilan iodé optimal.

Resumen

Concentraciones medianas de yodo urinario indicativas de una ingesta suficiente de yodo por la población

OBJETIVO: La concentración urinaria de yodo es el principal indicador del estado nutricional en cuanto a ese elemento y se utiliza para evaluar la administración de suplementos de yodo a nivel poblacional. En 1994, la OMS, el UNICEF y el CILTCY recomendaron concentraciones medianas de yodo urinario en poblaciones del orden de 100–200 µg/l, suponiendo que el umbral de 100 µg/l limitaría las concentraciones < 50 µg/l a £20% de las personas. Algunos científicos consideraron esta proporción inadmisiblemente alta y propusieron aumentar el umbral por encima de los 100 µg/l. El presente estudio se llevó a cabo para determinar la distribución de frecuencias de las concentraciones urinarias de yodo en poblaciones (escolares y adultos) que tenían las necesidades de yodo satisfechas, así como la proporción correspondiente de concentraciones <50 µg/l.
MÉTODOS: Se difundió entre 29 grupos científicos un cuestionario sobre la distribución de frecuencias del yodo urinario en poblaciones cubiertas en cuanto a las necesidades de yodo.
RESULTADOS: Diecinueve grupos notificaron datos de 48 poblaciones con concentraciones medianas de yodo urinario >100 µg/l. La población total ascendía a 55 892 personas, incluidos 35 661 (64%) escolares. Las concentraciones medianas de yodo urinario fueron de 111–540 (mediana 201) µg/l para todas las poblaciones, de 100–199 µg/l en 23 (48%) poblaciones y ³200 µg/l en 25 (52%) poblaciones. Las frecuencias de valores < 50 µg/lfueron de 0–20,8 (media 4,8%) a nivel general y de 7,2% y 2,5% en poblaciones con medianas de 100–199 µg/l y de más de 200 µg/l, respectivamente. La frecuencia sólo alcanzaba el 20% en dos lugares donde los suplementos de yodo se habían administrado durante menos de 2 años.
CONCLUSIÓN: Se ha sobreestimado la frecuencia de las concentraciones de yodo urinario < 50 µg/l en las poblaciones con niveles ³100 µg/l. No es necesario aumentar el umbral de 100 µg/l. A nivel poblacional, unas concentraciones medianas de yodo urinario de 100–200 µg/l son indicativas de una ingesta suficiente de yodo y de un aporte nutricional óptimo de este elemento.

References

1. WHO, UNICEF, ICCIDD. Indicators for assessing Iodine Deficiency Disorders and their control through salt iodization. Geneva:World Health Organization; 1994. WHO Document WHO/NUT/94.6.         

2. WHO, UNICEF, ICCIDD. Progress towards the elimination of Iodine Deficiency Disorders (IDD). Geneva: World Health Organization; 1999. WHO Document WHO/NHD/99.4.        

3. WHO, UNICEF, ICCIDD. Assessment of the Iodine Deficiency Disorders and monitoring their elimination. Geneva: World Health Organization; 2001. WHO Document WHO/NHD/01.1.        

4. Delange F, de Benoist B, Pretell E, Dunn JT. Iodine deficiency in the world. Where do we stand at the turn of the century? Thyroid 2001;11:437-47.        

5. Stanbury JB, Ermans AM, Bourdoux P, Todd C, Oken E, Tonglet, et al. Iodine- induced hyperthyroidism: occurrence and epidemiology. Thyroid 1998; 8:83-100.        

6. Wong GWK, Kwok MY, Ou Y. High incidence of juvenile Grave's disease in Hong Kong. Clinical Endocrinolology 1995;43:697-700.        

7. Wong GWK, Lam CWK, Kwok MY, Mak TWL, Ahuja AT, Chow CC, et al. Childhood goitre and urinary iodine excretion in Hong Kong. European Journal of Pediatrics 1998;157:8-12.        

8. Todd CH, Allain T, Gomo Z, Hasler JA, Ndiweni M, Oken E. Increase in thyrotoxicosis associated with iodine supplements in Zimbabwe. Lancet 1995;346:1563-4.        

9. Bourdoux P, Ermans AM, Mukalay AMW, Filetti S, Vigneri R. Iodine-induced thyrotoxicosis in Kivu, Zaire. Lancet 1996; 347:552-3.        

10. Delange F, de Benoist B, Alnwick D. Risks of iodine-induced hyperthyroidism following correction of iodine deficiency by iodized salt. Thyroid 1999;9:545-6.        

11. Rasmussen LB, Ovesen L, Christiansen E. Day-to-day and within-day variation in urinary iodine excretion. European Journal of Clinical Nutrition 1999; 53:401-7.        

12. Bürgi H, Bangerter B, Siebenhüner L. High day-to-day variability of urinary iodine excretion despite almost universal salt iodization in Switzerland. In: Geertman RM, editor. 8th World Salt Symposium. Volume 2. Amsterdam: Elsevier; 2000:961-3.        

13. Als C, Helbling A, Peter K, Haldiman M, Zimmerli B, Gerber H. Urinary iodine concentration follows a circadian rhythm: a study with 3023 spot urine samples in adults and children. Journal of Clinical Endocrinology and Metabolism 2000;85:1367-9.        

¹International Council for Control of Iodine Deficiency Disorders (ICCIDD), 153 Avenue de la Fauconnerie, 1170 – Brussels, Belgium (tel: 32 2 675 85 43; fax: 32 2 675 18 98; email: fdelange@ulb.ac.be). Correspondence should be addressed to this author.

²Department of Nutrition for Health and Development, World Health Organization, Geneva, Switzerland.

³Members of the Working Group: F. Azizi and R. Hajipour, Tehran, Iran; M. Benmiloud, Oran, Algeria; Z.P. Chen, Tianjin, China; J. Dussault, Quebec, Canada; L.C. Foo, Kuala Lumpur, Malaysia; R. Djokomoeljanto and B. Hartono, Semarang, Indonesia; J.G. Hollowell, CDC Atlanta, USA; M. Irie, Tokyo, Japan; P. Jooste, Tygerberg, South Africa; P. Laurberg, Aalborg, Denmark; B. Lozanov, Sofia, Bulgaria; E. Pretell, Lima, Peru; J. Rendl, Würzburg, Germany; S. Sinawat and P. Wongwatcharapaiboon, Bangkok, Thailand; K.M. Sullivan, Atlanta, USA; W.M. Wiersinga, Amsterdam, The Netherlands and M. Zimmermann, Zurich, Switzerland.

Ref. No. 01-1440