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Objective: This paper re-evaluates the requirements for iodine during pregnancy, lactation and the neonatal period, and formulates original proposals for the median concentrations of urinary iodine (UI) that indicate optimal iodine nutrition during these three critical periods of life. This paper also discusses the measurements that are used to explore thyroid functions during the same periods., Design: An extensive and critical review of the literature on thyroid physiopathology during the perinatal period., Setting: Human studies conducted in various regions throughout the world., Subjects: Pregnant women, lactating women, and newborns., Results: The following proposals are made after extensive review of the literature: the requirement for iodine by the mother during pregnancy is 250-300 microg day-1; during lactation the requirement is 225-350 microg day-1; and during the neonatal period the requirement of the infant is 90 microg day-1. The median UI that indicates an optimal iodine nutrition during these three periods should be in the range of 150-230 microg day-1. These figures are higher than recommended to date by the international agencies., Conclusions: Pregnant women and young infants, but especially the second group, are more sensitive to the effects of an iodine deficiency (ID) than the general population because their serum thyroid-stimulating hormone (TSH) and thyroxine are increased and decreased, respectively, for degrees of ID that do not seem to affect thyroid function in the general population. Systematic neonatal thyroid screening using primary TSH could be the most sensitive indicator to monitor the process of ID control.

The fetus is totally dependent in early pregnancy on maternal thyroxine for normal brain development. Adequate maternal dietary intake of iodine during pregnancy is essential for maternal thyroxine production and later for thyroid function in the fetus. If iodine insufficiency leads to inadequate production of thyroid hormones and hypothyroidism during pregnancy, then irreversible fetal brain damage can result. In the United States, the median urinary iodine (UI) was 168 microg/L in 2001-2002, well within the range of normal established by the World Health Organization (WHO), but whereas the UI of pregnant women (173 microg/L; 95% CI 75-229 microg/L) was within the range recommended by WHO (150-249 microg/L), the lower 95% CI was less than 150 microg/L. Therefore, until additional physiologic data are available to make a better judgment, the American Thyroid Association recommends that women receive 150 microg iodine supplements daily during pregnancy and lactation and that all prenatal vitamin/mineral preparations contain 150 microg of iodine.

Background: Severe iodine deficiency disorders have been eradicated in many parts of the world, but milder forms still exist and may escape detection. Turkey has long been known to be a mild to moderate iodine deficiency area., Aim of the Study: The aim of this study was to assess the iodine nutritional status and the thyroid function of pregnant women and their neonates in the region of Kayseri (central Anatolia of Turkey) that appeared to be iodine deficient in previous studies performed before the introduction of mandatory salt iodization., Methods: A cross-sectional voluntary screening study was performed in the Maternity Unit of a university hospital. A total of 70 mothers and their healthy full-term neonates were included in this study. Urinary iodine concentration was estimated in spot urine samples obtained from mothers and their neonates on day 5. All the neonates were breastfed. The iodine content was determined in the breast milk of all mothers on day 5. Serum concentrations of TSH, thyroglobulin (Tg), free triiodothyronine (FT3) and free thyroxine (FT4) were investigated in the cord serum of neonates and compared to those of mothers immediately after parturition, Results: The median urinary iodine on day 5 in mothers and their babies were 30.20 and 23.80 microg/l, respectively. These figures are much lower than normal for these age groups (150-200 microg/l). The median iodine content of breast-milk was 73 microg/l. It is again much lower than in iodine sufficient areas, indicating that the status of iodine nutrition of pregnant and lactating women is clearly insufficient. The median concentrations (and ranges) of neonatal TSH, Tg, FT3 and FT4 were 7.44 mU/l, 71.62 ng/ml, 1.30 pg/ml and 1.34 ng/dl respectively. The corresponding levels for the mothers during labor were 2.19 mU/l, 25.65 ng/ml, 1.31 pg/ml and 1.23 ng/dl respectively. The median neonatal serum concentrations of TSH and Tg were significantly higher than the corresponding maternal levels (P < 0.0001, P < 0.0001, respectively) and 27.1% of the neonates had serum TSH concentrations above 10 mU/l and 57.1 % had cord blood serum Tg concentrations above 54 ng/ml. None of the mothers showed TSH concentrations above 5 mU/l and 41.4% had serum Tg concentrations above 30 ng/ml., Conclusion: Iodine deficiency with low urinary iodine excretion and high serum Tg and TSH concentrations were recognized among pregnant women and their babies in Kayseri in spite of the program of salt iodization. National measures are urgently required for improving the correction of iodine deficiency in Turkey. This includes regular supplementation with iodine, starting at preconception or in early pregnancy and continuing during the period of nursing in this region.

Iodine deficiency has been a public health problem in most Latin American countries. Massive programs of salt iodization have achieved great progress toward its elimination but no consistent monitoring has been applied. We used the ThyroMobil model to visit 163 sites in 13 countries and assess randomly selected schoolchildren of both genders 6-12 years of age. The median urinary iodine concentration (8208 samples) varied from 72 to 540 microg/L. One national median was below the recommended range of 100-200 microg/L; five were 100-200 microg/L, and seven were higher than 200 microg/L, including three greter than 300 microg/L. Urinary iodine concentration correlated with the iodine content of salt in all countries. Median values of thyroid volume were within the normal range for age in all countries, but the goiter prevalence varied markedly from 3.1% to 25.0% because of scatter. The median iodine content of salt from local markets (2734 samples) varied from 5.9 parts per million (ppm) to 78 ppm and was greater than 15 ppm in 83.1% of all samples. Only seven countries had higher than 15 ppm iodine in 80% of the samples, and only three had greater than 15 ppm in at least 90%. Iodized salt was available at retail level in all countries but its median iodine content was within the recommended range (20-40 ppm) in only five. This study, the first to apply a standardized assessment strategy to recent iodine nutrition in Latin America, documents a remarkable success in the elimination of iodine deficiency by iodized salt in all but 1 of the 13 countries. Some iodine excess occurs, but side effects have not been reported so far, and two countries have already decreased their legal levels of salt iodization and improved the quality control of iodized salt, in part because of our results. The present work should be followed by regular monitoring of iodine nutrition and thyroid function, especially in the countries presently exposed to iodine excess.

Objective: Nearly two-thirds of the population of Western and Central Europe live in countries that are iodine deficient. Damage to reproductive function and to the development of the fetus and newborn is the most important consequence of iodine deficiency. The objective of this review was to examine the iodine status of pregnant women in Europe and the potential need for iodine supplementation., Design: A MEDLINE/PubMed search and compilation of all published studies since 1990 of iodine nutrition and iodine supplementation of pregnant women in Europe, as well as an Internet-based search and review on availability and legislation of iodine supplements in the European Union., Results: Although the data suggest most women in Europe are iodine deficient during pregnancy, less than 50% receive supplementation with iodine. Mild-to-moderate iodine deficiency during pregnancy adversely affects thyroid function of the mother and newborn and mental development of the offspring and these adverse effects can be prevented or minimized by supplementation. There are no published data on the effect of iodine supplementation on long-term maternal and child outcomes. The iodine content of prenatal supplements in Europe varies widely; many commonly used products contain no iodine. The European Union is developing legislation to establish permissible levels for iodine in food supplements., Conclusions: In most European countries, pregnant women and women planning a pregnancy should receive an iodine-containing supplement ( approximately 150 microg/day). Kelp and seaweed-based products, because of unacceptable variability in their iodine content, should be avoided. Prenatal supplement manufacturers should be encouraged to include adequate iodine in their products. Professional organizations should influence evolving EU legislation to ensure optimal doses for iodine in prenatal vitamin-mineral supplements., Sponsorship: International Council for Control of Iodine Deficiency Disorders.

Background: Goiter prevalence in school-age children is an indicator of the severity of iodine deficiency disorders (IDDs) in a population. In areas of mild-to-moderate IDDs, measurement of thyroid volume (Tvol) by ultrasound is preferable to palpation for grading goiter, but interpretation requires reference criteria from iodine-sufficient children., Objective: The study aim was to establish international reference values for Tvol by ultrasound in 6-12-y-old children that could be used to define goiter in the context of IDD monitoring., Design: Tvol was measured by ultrasound in 6-12-y-old children living in areas of long-term iodine sufficiency in North and South America, central Europe, the eastern Mediterranean, Africa, and the western Pacific. Measurements were made by 2 experienced examiners using validated techniques. Data were log transformed, used to calculate percentiles on the basis of the Gaussian distribution, and then transformed back to the linear scale. Age- and body surface area (BSA)-specific 97th percentiles for Tvol were calculated for boys and girls., Results: The sample included 3529 children evenly divided between boys and girls at each year ( +/- SD age: 9.3 +/- 1.9 y). The range of median urinary iodine concentrations for the 6 study sites was 118-288 micro g/L. There were significant differences in age- and BSA-adjusted mean Tvols between sites, which suggests that population-specific references in countries with long-standing iodine sufficiency may be more accurate than is a single international reference. However, overall differences in age- and BSA-adjusted Tvols between sites were modest relative to the population and measurement variability, which supports the use of a single, site-independent set of references., Conclusion: These new international reference values for Tvol by ultrasound can be used for goiter screening in the context of IDD monitoring.

The Czech Republic has a long history of iodine deficiency. Salt iodization was introduced in 1947, followed by a progressive correction of iodine deficiency. The present study reports the changes in the status of iodine nutrition and of thyroid function in the country from 1994 to 2002. The study included 29612 individuals, aged 0 to 98 years, including 5263 individuals randomly selected from the general population and 24349 individuals who attended the Institute of Endocrinology of Prague (hospital population). Urinary iodine was determined in all individuals. Measurements of serum thyrotropin (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and thyroglobulin (Tg), were taken in 8544 to 19060 individuals. The iodine content of table salt was measured in 1130 samples. The median urinary iodine in the general and hospital populations were not significantly different. They progressively increased with time, starting from values indicating mild iodine deficiency (88-95 microg/L) prior to 1997, reaching the critical threshold of 100 microg/L in 1998, and optimal values between 120-140 microg/L since 2000. There was only a low and not significant positive correlation between the iodine content of salt and the urinary iodine. In contrast, urinary iodine showed marked seasonal changes, with the highest values during winter, when livestock were supplemented by mineral tablets containing iodine. Variables exploring thyroid function were all situated within the normal range in adults but another study (results not reported) has shown the persistence of slightly elevated TSH in neonates. The correction of iodine deficiency was not accompanied by unfavorable side effects. In conclusion, the Czech Republic has achieved sustainable elimination of iodine deficiency. Salt iodization has been a determining, but not the only, factor responsible for the success. Iodine supplementation of livestock and increased consumption of milk rich in iodine have probably played a determining role. Neonatal thyroid screening could constitute the major monitoring tool in order to insure sustainable elimination of iodine deficiency in the Czech Republic.

The paper summarizes the updated information published in peer review journals on the status of iodine deficiency in Western and Central Europe. Nationwide evaluations of the prevalence of goiter and of the concentrations of urinary iodine were conducted during recent years in 17 of the 31 countries of Western and Central Europe, mostly in school-aged children. Fourteen of the 31 countries had reached a normal status of iodine nutrition, three countries were close to iodine sufficiency, iodine deficiency persisted in 13 other countries and data are missing for Albania. The most important alterations of thyroid function due to iodine deficiency in Europe occur in neonates and very young infants. The major measure for the prevention of iodine deficiency is the fortification of all salt for human and animal consumption and for the food industry. The recommended daily intake of iodine for all ages in all inhabitants in Europe are as follows: 90 microg/day from 0 to 59 month, 120 microg/day between 6 and 12 years, 100 microg/day in adolescents and adults and 200 microg/day in pregnant and lactating women. The main guidelines for the correction of iodine deficiency in Europe are included.

Unlabelled: Belgium used to be affected by mild iodine deficiency. Improvement in iodine nutrition has been recently documented in schoolchildren in Belgium in spite of the absence of any systematic programme of iodine supplementation. The question arises as to whether this 'silent iodine prophylaxis' affected also the neonates. A total of 185 random urine samples were collected from 90 full term and 65 preterm neonates in Brussels on day 5 and repeated on day 30 in 30 preterms who were bottle-fed with iodine-enriched formula-milk. The iodine content was also determined in 58 samples of breast-milk on day 5. The median urinary iodine on day 5 in full term neonates was 86 micro g/l, which is markedly higher than the figure of 48 micro g/L reported 15 years previously in neonates in the same area but still much lower than normal for this age group (150-200 micro g/l). The mean iodine content of breast-milk was 78 micro g/l, which is unchanged as compared to 15 years ago and is about 66% of normal. Finally, the median urinary iodine increased from 60 micro g/l on day 5 to 150 micro g/l on day 30 in preterms bottle-fed with iodine-enriched formula-milk., Conclusion: the status of iodine nutrition has also improved spontaneously in Belgian neonates but has not yet normalised. Lactating and probably pregnant women remain clearly iodine deficient. The iodine-enriched formula-milk for preterms is efficient in correcting their iodine deficiency. National measures are urgently required for correction of iodine deficiency in Belgium.

Monitoring and evaluation are the last phases of a national iodine deficiency disorders (IDD) control program but among the most important. This paper summarizes the latest recommendations by the World Health Organization (WHO), the United Nations Children's Fund (UNICEF), and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) about indicators and their normative values for monitoring the progress of IDD elimination and illustrates the successful monitoring programs in Switzerland and in China. Salt is the usual vehicle for iodine supplementation and quality control for iodine content can be assessed quantitatively by titration and qualitatively by simple test kits that can be used in the field. The most useful indicator of iodine nutrition is the median urinary iodine concentration. Thyroid size, especially by ultrasound, and neonatal thyrotropin (TSH) are also valuable. In Switzerland, access to iodized salt on a voluntary basis started in 1922. The initial level of iodization, 1.9-3.75 ppm iodine as potassium iodide (KI), was slowly increased to 15 ppm, and recently to 20 ppm, after careful epidemiologic and biologic monitoring. Elimination of IDD has been highly successful. The program costs US dollars 0.07 per year per person. In China, a national program of iodized salt (10-30 ppm) started in 1960 under the authority of the central government and rapidly expanded. National monitoring surveys have taken place every 2 years since 1993. Median urinary iodine, initially low, increased to 165 microg/L in 1995 and to 306 microg/L in 1999, prompting a decrease in the amount of iodine added to salt. The total goiter rate decreased to 20.4% in 1995 and to 8.8% in 1999. IDD can presently be considered as eliminated in China. Review of monitoring in the 128 other major countries affected by IDD shows extremely variable achievements, with evidence of IDD elimination in at least 18 additional countries. Some countries that were severely iodine deficient in the past are now exposed to iodine excess and risk its effects. Sustainable elimination of IDD is within reach and would constitute an unprecedented global success story in the field of noncommunicable diseases, but continuing vigorous action is required to attain this goal.

This paper updates the information on the prevalence of the disorders induced by iodine deficiency (IDD) in Europe. Thirty-two European countries were still affected by mild to severe iodine deficiency in the late 1990s. The most severely affected countries were in Eastern Europe, including Central Asia, but Western Europe was also still affected. National surveys recently conducted in 11 of these countries show that, with the exception of the Netherlands, none has yet reached a state of iodine sufficiency, though very significant improvement in the situation has been evidenced in many of them, e.g. Poland, Bulgaria and Macedonia. The consequences of persisting iodine deficiency are goitre, hyperavidity of the thyroid for iodide (which increases the risk of thyroid irradiation in the event of a nuclear accident) and subclinical hypothyroidism during pregnancy and early infant (with a concomitant risk of minor brain damage and irreversible impairment of the neuropsychointellectual development of offspring). Access to iodised salt at the household level in European countries affected by IDD increased from 5%-10% in 1990 to 28% in 1999. This constitutes encouraging progress. However, in terms of access of iodine-deficient countries to iodised salt, Europe remains the worst region in the world, as shown by the fact that the mean figure worldwide in 1999 was 68%. In Latin America it even reached 90%. Salt iodisation has to be further implemented in Europe. Until that goal is achieved, iodine supplementation in those groups most sensitive to the effects of iodine deficiency (pregnant and lactating women and young infants) will have to be considered in the most severely affected areas.

The major procedure used to correct iodine deficiency is the universal salt iodization by addition of iodide or iodate to salt with an iodine content varying from 7 to 100 mg/kg of salt depending on the country legislation. As an important fraction of consumers in the world prefers natural products over artificial ones, we investigated the industrial feasibility of naturally iodized salt using seaweed as source of iodine. We report the results of the iodine bioavailability in healthy subjects from two seaweeds: Laminaria hyperborea and Gracilaria verrucosa selected due to their high level in iodine as a mineral or an organic form and low levels of heavy metals. As a control we studied in a normal man the bioavailability of pure mineral iodine such as potassium iodide which was excellent i.e. 96.4% and of pure organic iodine such as monoiodotyrosine which was a little lower i.e. 80.0%. Iodine bioavailability from these two seaweeds was studied in nine normal subjects from Marseille (France) which is an iodine sufficient area based on a median urinary iodine level of 137 microg/day and innine normal subjects from Brussels (Belgium) who present a mild iodine deficiency with a value of 73 microg/day. The iodine bioavailability of Gracilaria verrucosa is better than for Laminaria hyperborea (101% versus 90% in Marseille, t=0.812, NS; 85% versus 61.5% in Brussels, t = 2.486, p = 0.024, S*). The urinary excretion of iodine is lower in Brussels than in Marseille for the same seaweed because part of the iodine is stored in the thyroid (101% versus 85% for Gracilaria verrucosa, t = 1.010, NS; 90% versus 61.5% for Laminaria hyperborea, t = 3.879, p= 0.001, S***).

Iodine deficiency disorders (IDD) is a major public health problem worldwide. WHO estimates that 740 million people are currently affected by goitre. The consequences of iodine deficiency on health are the results of hypothyroidism and the main one is impaired development of foetal brain. IDD is the first cause of preventable brain damage in children. The recommended strategy to correct IDD rests upon salt iodisation. Over the last 20 years, the international community mobilised to eliminate IDD under the leadership of WHO, Unicef and ICCIDD. It resulted in remarkable progress in IDD control, especially in Africa and in South East Asia where the endemic is the most severe. It is estimated that 68% of the populations of affected countries have currently access to iodised salt. However, out of the 130 affected countries, about 30 have no programme. Besides, salt quality control and monitoring of population iodine status are still weak in many countries, thus exposing the population to an excessive iodine intake and subsequently to the risk of iodine-induced hyperthyroidism. In addition, IDD is re-emerging in some countries, especially in Eastern Europe after it had disappeared. In order to reach the goal of IDD elimination, it is important to insist on the sustainability of salt iodisation programmes, which implies an increased commitment of both health authorities and representatives of the salt industry.

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 micro g/l, assuming the 100 micro g/l threshold would limit concentrations <50 micro g/l to 100 micro g/l. The total population was 55 892, including 35 661 (64%) schoolchildren. Median urinary iodine concentrations were 111-540 (median 201) micro g/l for all populations, 100-199 micro g/l in 23 (48%) populations and >/=200 micro g/l in 25 (52%). The frequencies of values <50 micro g/l were 0-20.8 (mean 4.8%) overall and 7.2% and 2.5% in populations with medians of 100-199 micro g/l and >200 micro g/l, respectively. The frequency reached 20% only in two places where iodine had been supplemented for <2 years., Conclusion: The frequency of urinary iodine concentrations <50 micro g/l in populations with median urinary iodine concentrations >/=100 micro g/l has been overestimated. The threshold of 100 micro g/l does not need to be increased. In populations, median urinary iodine concentrations of 100-200 micro g/l indicate adequate iodine intake and optimal iodine nutrition.

Objective: To evaluate the long-term efficacy and possible side effects of low doses of iodized oil on iodine nutrition and thyroid function in endemic goiter in Romania., Methods: Random selection of 214 schoolchildren aged 6-14 years. Serial measurements of urinary iodine, thyroid volume with ultrasound, serum concentrations of thyrotropin, free thyroxine, thyroglobulin and thyroid autoantibodies before and up to 2 years after the oral administration of 200 mg iodine in iodized oil., Results: Urinary iodine concentrations indicated a moderate iodine deficiency before therapy, sharply increased soon after therapy and slowly decreased thereafter but remained within the normal range up to more than 1 year after therapy. The prevalence of goiter was 29% before the administration of iodized oil and 9% 1 year later. Thyroid function tests and autoantibodies were normal before and up to 2 years after therapy., Conclusion: A single dose of 200 mg iodine from oral Lipiodol appears adequate and safe for correcting moderate iodine deficiency in children., (Copyright 2002 S. Karger AG, Basel)

Iodine is essential for normal growth, mental development, and survival of infants. The main source of iodine for breastfeeding infants is the iodine found in human milk. Despite the importance of iodine for infant health, there have been limited studies addressing human milk iodine concentrations. The newly recommended Adequate Intake of iodine for infants is 110 microg/day for infants 0-6 months and 130 microg/day for infants 7-12 months. Further studies of human milk iodine are needed to ensure that iodine prophylaxis is providing sufficient iodine for mothers and infants worldwide.

Iodine deficiency is the leading cause of preventable mental retardation. Universal salt iodization (USI), calling for all salt used in agriculture, food processing, catering and household to be iodized, is the agreed strategy for achieving iodine sufficiency. This article reviews published information on programs for the sustainable elimination of the iodine deficiency disorders and reports new data on monitoring and impact of salt iodization programs at the population level. Currently, 68% of households from areas of the world with previous iodine deficiency have access to iodized salt, compared to less than 10% a decade ago. This great achievement, a public health success unprecedented in the field of noncommunicable diseases, must be better recognized by the health sector, including thyroidologists. On the other hand, the managers and sponsors of programs of iodized salt must appreciate the continuing need for greatly improved monitoring and quality control. For example, partnership evaluation of iodine nutrition using the ThyroMobil model in 35,223 schoolchildren at 378 sites of 28 countries has shown that many previously iodine deficient parts of the world now have median urinary iodine concentrations well above 300 microg/L, which is excessive and carries the risk of adverse health consequences. The elimination of iodine deficiency is within reach but major additional efforts are required to cover the whole population at risk and to ensure quality control and sustainability.

The Professor F. Delange has a substantial experience, since the last decade, in implementing universal salt iodization in a lot of countries, and assessing its impact on iodine deficiency disorders. He comments here the published results of D.E. Hindié et al. concerning the side effects of stable iodine overload on thyroid structure in the young rat (N. Colas-Linhart).

Background: Iodine prophylaxis in Poland started in 1935 and has been interrupted twice: by World War II and in 1980 for economic reasons. Epidemiological surveys carried out after the Chernobyl accident in 1989 as well as in 1992/1993 and in 1994 as a 'ThyroMobil' study, revealed increased prevalence of goitre in children and adults. Ninety per cent of Poland was classified as an area of moderate iodine deficiency, and 10%, in the seaside area, as mild iodine deficiency territory. Iodine prophylaxis based on iodisation of household salt was introduced again in 1986 as a voluntary model and in 1997 as a mandatory model with 30+/-10 mg KI/kg salt., Objective: The evaluation of the obligatory model of iodine prophylaxis in schoolchildren from the same schools in 1994 and 1999., Methods: Thyroid volume was determined by ultrasonography. Ioduria in casual morning urine samples was measured using Sandell-Kolthoff's method, within the framework of the ThyroMobil study., Results: Goitre prevalence decreased from 38.4 to 7% and urinary iodine concentration increased from 60.4 to 96.2 microg/l mean values between 1994 and 1999. In four schools the prevalence of goitre diminished below 5%. In 1999, 70% of children excreted over 60 microg I/l, and 36% over 100 microg I/l, whereas in 1994 the values were 44 and 13% respectively., Conclusion: The present findings indicate that iodine prophylaxis based only on iodised household salt is highly effective.

Iodine deficiency is well documented in Belgium in adults including pregnant women, adolescents, schoolchildren, and neonates, but no data are available in the age group 6 months-3 years. We investigated the status of iodine nutrition in 111 healthy subjects in this age group in an attempt to evaluate the risk of brain damage due to iodine deficiency in Belgium. In 244 causal urine samples collected in these subjects, the median concentration of iodine was 101 micrograms/l vs 180-220 micrograms/l under normal conditions. The daily supplementation of the subjects with a physiological dose of 90 micrograms iodine was followed by a slow and progressive increase of urinary iodine, which reached a normal level only after a delay of about 30 weeks of therapy. This observation suggests that part of the supplement of iodine offered to the children was stored in their thyroid glands until the iodine content of the gland had reverted to normal, reflecting the state of hyperavidity of the thyroid for iodide characteristic of iodine deficiency. In conclusion, infants and young children in Belgium are as iodine deficient as all other age groups of the population and, consequently, are at risk of brain damage. This works further illustrates the need for systematic iodine supplementation of the population in Belgium.

Indonesia used to be affected by varying degrees of iodine deficiency. Salt iodization has been the adopted strategy on a national basis since 1979. The prevalence of goiter in school-age children (SAC) determined by palpation subsequently markedly decreased within the next 15 years. The objective of the present work was to perform an updated evaluation of the status of iodine nutrition in Indonesia by using standardized methods for the measurement of thyroid volume by ultrasounds and the concentration of urinary iodine in SAC. The survey included 7,447 SAC ages 6 to 12 years from 129 sites selected by multistage and stratified sampling in five provinces (4 in Java plus Sumatra and the Province of Bali). A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites. In Java plus Sumatra, the median urinary iodine was 195 microg/L. Thirty-four percent of the values were within normal limits (between 100 and 200 microg/L); 17.2% were below 100 microg/L and 48.8% were above 200 microg/L, including 18.2% above 300 microg/L and 0.7% above 1000 microg/L. In Bali, the median was 81 microg/L with 58.3% of the values below 100 microg/L and only 14.7% of the values above 200 microg/L. The prevalence of goiter determined by ultrasounds and using the World Health Organization/International Council for Control of Iodine Deficiency Disorders (WHO/ICCIDD) normative values for gender and age was 3.0% in Java plus Sumatra and 1.9% in Bali. The values were 8.0% and 12.5%, respectively, when using reference values for Indonesia established during the present survey in an iodine replete area in central Java. In conclusion, (1) iodine deficiency has been eliminated in large parts of Indonesia; (2) Bali is still affected by mild iodine deficiency; (3) in many places, iodine deficiency has been replaced by iodine excess, occasionally potentially toxic; (4) the WHO/ICCIDD normative values for thyroid volume measured by ultrasound in SAC are not valid for Indonesia; (5) in Indonesia, the level of salt iodization could be decreased and the biological monitoring of urinary iodine at the population level should be reinforced and maintained; (6) the ThyroMobil model has, as in other parts of the world, demonstrated its efficiency in the organization of partnership evaluation and monitoring of iodine nutrition, as well as in social mobilization.

Objective: Interpretation of thyroid ultrasonography for assessing goiter prevalence requires valid reference criteria from iodine-sufficient populations. Reports have suggested the current reference criteria for thyroid volume (T(vol)) of WHO/ICCIDD (International Council for the Control of Iodine Deficiency Disorders) may be too high. Our objective was to determine if inter-observer and/or inter-equipment variability contributes to the disagreement in sonographic T(vol) in children reported from iodine-sufficient areas., Design: A 2-day workshop in which four experienced ultrasound examiners from around Europe measured T(vol) in 45 6--12-year-old Swiss schoolchildren using four different portable ultrasound machines. One of the participating examiners (observer A) had generated the T(vol) data in European children that are the basis for the WHO/ICCIDD reference criteria., Methods: Sonographic T(vol) was measured in each child by all four examiners on all four machines. Six hundred and eighty-four examinations were completed, with examiners having no knowledge of one another's results. Inter-observer and inter-equipment variation was calculated., Results: Mean inter-equipment variation in T(vol) was 15.2% (95% CI: 14.1, 16.3%). There were no significant differences in T(vol) between equipment (P=0.51). For all observers, the mean inter-observer variation in T(vol) was 25.6% (95% CI: 23.9, 27.2%). At all ages and all body surface areas, there was a large systematic measurement bias (+30% volume) between the mean T(vol) of observer A and the mean Tvol of observers B, C and D. Reanalysis using data from observers B, C and D reduced the mean inter-observer variation in T(vol) to 13.3% (95% CI: 11.9, 14.7%). A correction factor for the systematic difference of operator A for the P50 and P97 of T(vol) was estimated using analysis of covariance. When applied to the WHO/ICCIDD reference data, it sharply reduced the discrepancy between the WHO/ICCIDD criteria and those from other iodine-sufficient children around the world., Conclusions: Inter-equipment error contributes minimally to reported differences in sonographic T(vol). Even among experienced examiners, inter-observer variation in sonographic T(vol) in children can be high, and probably contributes to the current disagreement on normative values in iodine-sufficient children. A systematic bias at least partially explains why the WHO/ICCIDD reference data differ from those reported from other iodine-sufficient children around the world. The findings argue strongly for the standardization of methods used for sonographic measurement of T(vol) in children.

The adequate functioning of both the maternal and fetal thyroid glands play an important role to ensure that the fetal neuropsycho-intellectual development progresses normally. Three sets of clinical disorders are considered, that may eventually lead to impaired brain development. Firstly, in infants with a defect of glandular ontogenesis (congenital hypothyroidism), the participation of maternal thyroid hormones to the fetal circulating thyroxine environment is normal and, therefore, risk of brain damage results exclusively from the insufficient hormone production by the abnormal fetal thyroid gland. Secondly, when it is only the maternal thyroid gland that is functionally deficient (autoimmune hypothyroidism), the severity and temporal occurrence of maternal underfunction will both drive the resulting consequences for impaired fetal neuronal development. Clinical situations of this type may obviously take place already during early gestation (in women with known but untreated hypothyroidism) or appear only during later gestational stages (in women who have AITD and remain euthyroid during the first half of gestation). Lastly, in conditions with iodine deficiency, both maternal and fetal thyroid functions are affected and, therefore, it is primarily the degree and precocity of the maternal hypothyroxinemia due to iodine deficiency during pregnancy that will drive the potential repercussions for fetal neurological development. In the present review, we summarize available data and develop our present concepts concerning the complex feto-maternal thyroid relationships and the potential impacts of thyroid function abnormalities on the ideal development of the offspring.

Objective: Belgium is one of the Western European countries in which no program of iodine-deficiency correction using iodized salt has been implemented, in spite of well-documented mild iodine deficiency. In 1995, the median urinary iodine concentration was 55 microg/l (normal: 100-200) and the prevalence of goiter was 11% (normal: below 5%) in representative samples of schoolchildren aged 6-12 years. Based on these results, the authors of the present study and others had emphasized to health professionals and to the public the necessity for iodine supplementation. The objective of this study was to evaluate as to whether these efforts had resulted in an improvement in the status of iodine nutrition., Design: We performed a national survey of the status of iodine nutrition in Belgium based on the determination of thyroid volume, obtained by ultrasonography, and urinary iodine concentrations in schoolchildren., Methods: A mobile van equipped with an ultrasound instrument, a computer and a deep-freeze visited 23 schools selected from across the country. The sample included 2855 schoolchildren (1365 boys and 1490 girls) aged 6-12 years., Results: The results show a homogeneous situation in the whole country, with a median urinary iodine concentration of 80 microg/l and a goiter prevalence of 5.7%. Urinary iodine slightly decreases with age in girls and reaches a critical value of 59 microg/l at the age of 12 years, together with a goiter prevalence of 18.4%., Conclusion: Iodine nutrition has improved slightly in Belgium but mild iodine deficiency continues, with public-health consequences. The improvement indicates silent iodine prophylaxis, as no official salt-iodization measures have been taken. Silent iodine prophylaxis only partly corrects iodine deficiency in Western Europe. Active measures, including the implementation of a program of salt iodization, are urgently required.

Unlabelled: While performing a systematic ultrasound study of the thyroid gland volume for the evaluation of iodine deficiency in 2845 normal Belgian school children, we found an absence of the left lobe in 6 children (4 girls and 2 boys). There was no association with other thyroid malformations or dysfunction., Conclusion: This first systematic ultrasound evaluation of thyroid hemiagenesis in normal children established a prevalence of thyroid hemiagenesis of 0.2% and confirmed the female predominance and higher incidence of agenesis of the left lobe.

We report a Belgian girl born in 1983 with isolated thyrotropin (TSH) deficiency. Hypothyroidism without goiter was diagnosed at the age of 2 months, with extremely low total thyroxine (T4) at 0.3 microg/dL (4 nmol/L; N[normal]: 5.6-11.4 microg/dL). Basal TSH, only moderately elevated at 14.8 mU/L (N: 0-5.3; competitive radioimmunoassay, RIA), increased to 18.2 mU/L after thyrotropin-releasing hormone (TRH) stimulation, whereas prolactin increased normally. At age 15 years, after withdrawal of levothyroxine (LT4) therapy for 6 weeks, TRH stimulation slightly increased serum TSH using two immunometric assays, from less than 0.03 to 0.07 and from 0.2 to 0.3 (a monoclonal and polyclonal antibody), and from 1.9 to 4.1 mU/L using a polyclonal TSH antibody and iodinated recombinant TSH. Sequencing of the TSH-beta subunit gene revealed a homozygous single nucleotide deletion in codon 105 producing a frame shift that results in a truncated TSH-beta with nonhomologous 9 carboxyterminal amino acids and a loss of the 5 terminal residues. This mutation was previously reported in one Brazilian and two German families. The abnormal, and presumably biologically inactive, TSH can be detected in serum using appropriate antibodies. Its relatively small amount in serum is due to either reduced secretion or rapid degradation. The occurrence of the same mutation in three families of different ethnic origin suggests that this mutation may be prevalent in the population. Common ancestry or de novo mutations in a hot spot cannot be excluded. Finally, we must be aware that neonatal screening of congenital hypothyroidism based on blood spot TSH measurement will not detect this rare but severe genetic defect.

In 1990, iodine deficiency affected almost one-third of the world population and was the greatest single cause of preventable brain damage and mental retardation. Following a resolution adopted by the World Summit for Children in 1990. major programmes of iodine supplementation were implemented by the governments of the affected countries with the support of major donors. Iodisation of salt was recognised as the method of choice. Nine years later, by April 1999, 75% of the affected countries had legislation on salt iodisation and 68% of the affected populations had access to iodised salt. The prevalence of iodine deficiency disorders decreased drastically in most countries and the deficiency disappeared completely in some such as Peru. This result constitutes a public heath success unprecedented with a non-infectious disease. However, occasional adverse effects occurred. The principle effect is iodine-induced hyperthyroidism which occurs essentially in older people with autonomous nodular goitres, especially following iodine intake that is too rapid and of too massive an increment. The incidence of the disorder is usually low and reverts spontaneously to the background rate of hyperthyroidism or even below this rate after 1 to 10 years of iodine supplementation. The possible occurrence of iodine-induced thyroiditis in susceptible individuals has not been clearly demonstrated by large epidemiological surveys. Iodine supplementation is followed by an increased prevalence of occult papillary carcinoma of the thyroid discovered at autopsy but the prognosis of thyroid cancer is improved due to a shift towards differentiated forms of thyroid cancer that are diagnosed at earlier stages. Iodine-induced hyperthyroidism and other adverse effects can be almost entirely avoided by adequate and sustained quality control and monitoring of iodine supplementation which should also confirm adequate iodine intake. Available evidence clearly confirms that the benefits of correcting iodine deficiency far outweigh the risks of iodine supplementation.

I is required for the synthesis of thyroid hormones. These hormones, in turn, are required for brain development, which occurs during fetal and early postnatal life. The present paper reviews the impact of I deficiency (1) on thyroid function during pregnancy and in the neonate, and (2) on the intellectual development of infants and children. All extents of I deficiency (based on I intake (microgram/d); mild 50-99, moderate 20-49, severe > 20) affect the thyroid function of the mother and neonate, and the mental development of the child. The damage increases with the extent of the deficiency, with overt endemic cretinism as the severest consequence. This syndrome combines irreversible mental retardation, neurological damage and thyroid failure. Maternal hypothyroxinaemia during early pregnancy is a key factor in the development of the neurological damage in the cretin. Se deficiency superimposed on I deficiency partly prevents the neurological damage, but precipitates severe hypothyroidism in cretins. I deficiency results in a global loss of 10-15 intellectual quotient points at a population level, and constitutes the world's greatest single cause of preventable brain damage and mental retardation.

Endemic goitre is still an important and underestimated health concern in Turkey. The overall prevalence had been calculated as 30.3% by palpation in a national survey conducted in 1995. However, direct evidence that iodine deficiency (ID) is the major cause of the endemic were lacking until now. We measured sonographic thyroid volumes (STV), urinary iodine concentrations (UIC) in 1226 school age children (SAC) (9-11 year old) from Ankara the capital of Turkey located in the central Anatolia, and three highly endemic goitre areas of the Black Sea region. A considerable number of school age children (SAC) were found to have STV exceeding the recommended upper normal limits for their age and gender obtained from iodine-replete European children (i.e. 26.7, 40.3, 44.8 and 51.7% of children from Ankara, Kastamonu, Bayburt and Trabzon respectively). UIC indicated moderate to severe ID in these areas with median concentrations of 25.5, 30.5, 16.0 and 14 microg/L respectively. This study showed severe to moderate ID as the primary etiological factor for the goitre endemic observed in Ankara and the Black Sea region of Turkey.

In conditions of iodine deficiency, the frequency distribution of neonatal thyroid-stimulating hormone (TSH) is shifted towards elevated values. Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore constitutes the only indicator that allows prediction of brain damage, which is the main complication of iodine deficiency. This paper reviews studies on neonatal thyroid function in iodine deficiency and confirms the former statement by WHO/UNICEF/ICCIDD that the frequency of neonatal TSH above 5 mU/L blood is below 3% in conditions of normal iodine supply, that a frequency of 3-19.9% indicates mild iodine deficiency and that frequencies of 20-39.9% and above 40% indicate moderate to severe iodine deficiency, respectively. Neonatal thyroid screening appears as a particularly sensitive index in the monitoring of iodine supply at a population level.

The light-induced conformational changes of rhodopsin, which lead to the formation of the G-protein activating metarhodopsin II intermediate, are studied by polarized attenuated total reflectance infrared difference spectroscopy. Orientations of protein groups as well as the retinylidene chromophore were calculated from the linear dichroism of infrared difference bands. These bands correspond to changes in the vibrational modes of individual molecular groups that are structurally active during receptor activation, i.e., during the rhodopsin to metarhodopsin II transition. The orientation of the transition dipole moments of bands previously assigned to the carboxyl (C=O) groups of Asp83 and Glu113 has been determined. The orientation of specific groups in the retinylidene chromophore has been inferred from the dichroism of the bands associated with the polyene C-C, C=C, and hydrogen-out-of-plane vibrations. Interestingly, the use of polarized infrared light reveals several difference bands in the rhodopsin to metarhodopsin II difference spectrum which were previously undetected, e.g., at 1736 and 939 cm(-1). The latter is tentatively assigned to the hydrogen-out-of-plane mode of the HC(11)=C(12)H segment of the chromophore. Our data suggest a significant change in orientation of this group in the late phase of rhodopsin activation. On the basis of available site-directed mutagenesis data, bands at 1406, 1583, and 1736 cm(-1) are tentatively assigned to Glu134. The main features in the amide regions in the dichroic difference spectrum are discussed in terms of a slight reorientation of helical segments upon receptor activation.

Biochemical signs of hyperthyroidism, or even overt and possibly lethal clinical hyperthyroidism were reported in 2 severely iodine-deficient African countries (Zimbabwe and Democratic Republic of Congo, RDC) soon after the introduction of iodized salt. The 2 countries had access to iodized salt produced in Botswana, as well as 5 other countries in the region, namely Cameroon, Nigeria, Kenya, Tanzania, and Zambia. Therefore, a multicenter study was conducted in these 7 countries to evaluate whether the occurrence of iodine-induced hyperthyroidism (IIH) after the introduction of iodized salt was a general phenomenon or corresponded to specific local situations in the 2 affected countries. Two or 3 areas with a past history of severe iodine deficiency that had recently been supplemented with iodized salt were selected in each of the 7 countries. The prevalence of goiter was determined in 4423 schoolchildren in these areas and the concentration of urinary iodine in 2258. Salt factories and health structures were visited for the evaluation of the quality of iodized salt and the possible occurrence of IIH. The study showed that iodine deficiency had been eliminated in all areas investigated, and that the prevalence of goiter had markedly decreased since the introduction of iodized salt. This is a remarkable achievement in terms of public health. However, some areas were now exposed to iodine excess due mostly to a poor monitoring of the quality of the iodized salt and of the iodine intake of the population. In these areas or countries, IIH occurred only when the introduction of iodized salt had been of recent onset (<2 years), namely in Zimbabwe and RDC. In conclusion, the risk of IIH after correction of iodine deficiency is closely related to a recent excessive increment of iodine supply.

Data in the literature suggest a finely tuned interaction between ligand (11-cis-retinal) and protein (opsin) in order to allow very efficient photoactivation of the ligand and highly vectorial rhodopsin activation with a huge increase in receptor activity. We have further investigated this interaction using ligand homologues, 13C-ligand labelling or 15N-protein labelling, in combination with Fourier transform infrared (FT-IR) and solid-state magic angle spinning (ss-MAS)-NMR spectroscopy. Using 1D rotational resonance (RR) or double-quantum heteronuclear local field (2Q-HLF) ss-MAS-NMR we report the first structure refinement of the rhodopsin chromophore in situ. These measurements yield a specification of the torsional strain in the for isomerization essential C10-C13 segment of the chromophore. This strain is thought to contribute to the high rate and stereospecificity of the photoisomerization reaction. In agreement with previous data, the C10-C13 segment region reaches a relaxed all-trans configuration at the lumirhodopsin photointermediate. MAS-NMR analysis of [15N]lysine-labelled rhodopsin reveals the presence of a 'soft' counterion, requiring intermediate water molecules for stabilization. FT-IR studies on [2H]tyrosine-labelled rhodopsin demonstrate participation of several tyrosin(at)e residues in receptor activation. One of these, probably Tyr268, is already active at the bathorhodopsin stage. Finally, the effect of ligands with single additional methyl substituents in the C10-C12 region has been investigated. They do not affect the general activation pathway, but perturb the activation kinetics of rhodopsin, suggesting steric interference with protein residues. Possible implications of these results for a structural role of water residues will be discussed, as well.

Neonatal thyroid screening using serum thyrotropin (TSH) as the primary screening test detects not only permanent sporadic congenital hypothyroidism, whose incidence is about 1 per 4000 births, but also compensated or transient primary hypothyroidism, whose incidence can be as high as 1 in 10 neonates and whose main cause is iodine deficiency. Elevated serum TSH in the neonate indicates insufficient supply of thyroid hormones to the developing brain, and therefore, constitutes the only indicator that allows prediction of possible impairment of mental development at a population level, which is the main consequence of iodine deficiency. Therefore, the World Health Organization (WHO), United Nations International Children's Emergency Fund (UNICEF), and the International Council for Control of Iodine Deficiency Disorders (ICCIDD) included neonatal TSH as one of the indicators for assessing iodine deficiency disorders (IDD) and their control. In the absence of iodine deficiency, the frequency of neonatal TSH above 5 mU/L whole blood (or 10 mU/L serum) is less than 3%. A frequency of 3%-19.9% indicates mild IDD. Frequencies of 20%-39.9% and above 40% indicate moderate and severe IDD, respectively. Neonates exhibit elevated serum TSH more frequently than adults for a similar degree of iodine deficiency. Consequently, they appear hypersensitive to the effects of iodine deficiency. This characteristic is explained by a particularly low iodine content of the thyroid of neonates and, consequently, by an accelerated turnover rate of their intrathyroidal iodine reserves. This turnover rate is 1% in adults. It is 17% in the neonate in conditions of iodine repletion, but is as high as 62% and 125% in conditions of moderate and severe iodine deficiency, respectively. Such an accelerated turnover rate requires thyroid hyperstimulation by TSH that is morphologically evidenced even in moderately iodine deficient neonates. Neonatal screening using primary TSH is implemented in most countries with mild IDD where it detects the cases of sporadic, permanent congenital hypothyroidism and where it is also used as a monitoring tool for IDD evaluation and control. However, the implementation of such programs in countries affected by moderate or severe IDD is still insufficient because of lack of resources of the countries. This should be considered in the framework of the external support often provided to these countries for the implementation of programs of universal salt iodization. Monitoring of these programs in order to achieve the goal of sustainable elimination of IDD now constitutes an absolute priority.

We present the first Fourier transform infrared (FTIR) analysis of an isotope-labeled eukaryotic membrane protein. A combination of isotope labeling and FTIR difference spectroscopy was used to investigate the possible involvement of tyrosines in the photoactivation of rhodopsin (Rho). Rho --> MII difference spectra were obtained at 10 degrees C for unlabeled recombinant Rho and isotope-labeled L-[ring-2H4]Tyr-Rho expressed in Spodoptera frugiperda cells grown on a stringent culture medium containing enriched L-[ring-2H4]Tyr and isolated using a His6 tag. A comparison of these difference spectra revealed reproducible changes in bands that correspond to tyrosine and tyrosinate vibrational modes. A similar pattern of tyrosine/tyrosinate bands has also been observed in the bR --> M transition in bacteriorhodopsin, although the sign of the bands is reversed. In bacteriorhodopsin, these bands were assigned to Tyr-185, which along with Pro-186 in the F-helix, may form a hinge that facilitates alpha-helix movement.

Iodine deficiency still exists in many countries worldwide, to a certain degree this is also true for Germany. Food of animal origin can be a good source for iodine depending on the feed. To investigate the possible use of laying hen feed enriched with iodine, we conducted a feeding experiment with 40 laying hens receiving feed with different amounts of iodine either as KIO3 or in the form of seaweed. Iodine concentration in eggs increased significantly depending on iodine intake after a 2 week period. Seaweed could also be used as an iodine source by the hens. A subsequent consumption study with 24 volunteers showed that eggs enriched with iodine can increase human's iodine excretion and therefore improve human's iodine supply. This new strategy is thought to accompany salt iodization programs, not to replace them.

The present study focuses on ligand-protein interactions in a rhodopsin analogue generated from bovine opsin and the 10-methyl homologue of 11-cis-retinal. The analogue pigment displays a reduced alpha-band at 506 +/- 2 and a stronger beta-band at 325 nm. Remarkably, the rotational strength of these bands observed in visible circular dichroism spectra was found to be similar for both native and 10-methyl rhodopsin. The quantum yield of the analogue pigment was determined to be 0.55. All photointermediates were analyzed by Fourier transform infrared difference spectroscopy. At the batho stage, strong hydrogen-out-of-plane vibrations were observed, indicating that the 10-methyl chromophore also adopts a distorted all-trans conformation at this stage. In contrast to native rhodopsin, the batho intermediate of the 10-methyl pigment is stable up to 180 K and only slowly decays to the next intermediate between 180 and 210 K. As in native rhodopsin, the 10-methyl metarhodopsin I intermediate is generated at about 220 K, but its transition to the metarhodopsin II state is again shifted to a much higher temperature (> 293 K) than for the native pigment (> 260 K). Infrared analysis, nevertheless, shows that the conformational changes in the photointermediates of the 10-methyl pigment are basically identical with those observed in the native pigment. This is supported by a signal function assay, showing that the analogue pigment is able to activate transducin. The dual effect of the 10-methyl group on the photocascade is attributed to steric interactions which, initially, hamper the relaxation of strain in the polyene chain of the chromophore and, eventually, interfere with the conformational rearrangements of the protein moiety required to adopt the active conformation of the receptor. Our data provide direct support for the concept that the relaxation of strain in the retinal polyene chain acts as the major driving force of the photocascade dark reaction.

Rhodopsin is a 7-helix, integral membrane protein found in the rod outer segments, which serves as the light receptor in vision. Light absorption by the retinylidene chromophore of rhodopsin triggers an 11-cis-->all-trans isomerization, followed by a series of protein conformational changes, which culminate in the binding and activation of the G-protein transducin by the metarhodopsin II (Meta II) intermediate. Fourier transform IR difference spectroscopy has been used to investigate the structural changes that water, as well as other OH- and NH-containing groups, undergo during the formation of the metarhodopsin I (Meta I) and Meta II intermediates. Bands associated with the OH stretch modes of water are identified by characteristic downshifts upon substitution of H2(18)O for H2O. Compared with earlier work, several negative bands associated with water molecules in unphotolysed rhodopsin were detected, which shift to lower frequencies upon formation of the Meta I and Meta II intermediates. These data indicate that at least one water molecule undergoes an increase in hydrogen bonding upon formation of the Meta I intermediate, while at least one other increases its hydrogen bonding during Meta II formation. Amino acid residue Asp-83, which undergoes a change in its hydrogen bonding during Meta II formation, does not appear to interact with any of the structurally active water molecules. Several NH and/or OH groups, which are inaccessible to hydrogen/deuterium exchange, also undergo alterations during Meta I and Meta II formation.

Review of available literature and experience supports a recommended daily iodine intake of 150 microg for adults, 200 microg during pregnancy, 50 microg for the first year of life, 90 microg for ages 1 to 6, and 120 microg for ages 7 to 12. The amount of iodine added to salt in fortification programs should be adjusted to achieve these intakes. Iodine-induced hyperthyroidism (IIH) is an occasional consequence of the correction of iodine deficiency, occurring most frequently in older subjects with multinodular goiter. This complication is usually mild and self-limited, but may be serious and occasionally lethal. The most important clinical manifestations are cardiovascular. Thyrotoxicosis can aggravate pre-existing cardiac disease and can also lead to atrial fibrillation, congestive heart failure, worsening of angina, thromboembolism, and rarely, death. In the absence of pre-existing cardiac disease, treatment of thyrotoxicosis usually returns cardiac function to normal. Heightened awareness on the part of the health sector will promote early detection and prompt treatment of IIH. Monitoring should be an important part of a successful program of iodization, and in addition it offers the best opportunity for recognizing and treating IIH. Further research to improve the characterization and prevention of IIH is strongly encouraged. The most important conclusion is that IIH, while an issue that needs serious address, is not a reason to stop iodine supplementation in deficient regions. The benefits to the community from correcting iodine deficiency and avoiding its associated disorders far outweigh the damage from IIH.

This paper reviews all presently available data on iodine nutrition in Belgium. All age groups have an iodine intake below the recommendations by WHO. The main consequences are subclinical hypothyroidism with goiter during pregnancy and a risk of transient hypothyroidism resulting in minor brain damage in the neonate. Moreover the cost of therapy of IDD in Belgium is about one billion BEF of which some 75% could be avoided by well controlled and monitored iodine prophylaxis in the country. Such a program should be implemented.