Volume 9 Number 1, February 1993

IN THIS ISSUE

Iodine Deficiency Persists in Europe

Europe has supported IDD elimination in developing countries but generally ignored its own IDD problems. This indifference was partly reversed in a workshop entitled "Iodine Deficiency in Europe: A Continuing Concern" that took place in Brussels in April 1992 and reviewed the status of iodine nutrition internationally, with a particular focus on individual European countries. Other topics included iodine nutrition, the role of iodine in thyroid pathophysiology, techniques of evaluation, and the consequences of iodine deficiency, particularly those on pregnant women, neonates, and populations exposed to nuclear hazards. The chairman of the organizing committee was Dr. Francois Delange, ICCIDD Regional Coordinator for Europe and Professor of Pediatrics at the Free University of Brussels. Sponsors included ICCIDD, NATO, WHO, UNICEF, the Commission of the European Communities, the European Thyroid Association, FNRS Belgium, the Free University of Brussels, Ministry of Public Health Belgium, and the French community of Belgium. Major financial sponsors were Christiaens S.A., Brussels, Belgium; Henning, Berlin GMBH, Germany; Laboratoire Guerbet, Aulnay-sous-Bois, France; E. Merck, Darmstadt, Germany; Nutricia S.A., Rijkswijk, Belgium; Rhone-Poulenc, Rorer-Antony, France; SQM Iodine Europe, Antwerp, Belgium; Trosol, Brussels, Belgium; ACEC, Union Minière, Charleroni, Belgium; Biogam, Liège, Belgium; Boots Pharmaceuticals, USA; Electricite de France, Paris, France; Serono, Boulogne, France; Malinckrodt Medical, Nestle-Guigoz, Pfizer, Sanofi-Pharma, Solvay S.A., Brussels, Belgium.

A previous Newsletter (May 1992, vol. 8, no. 2) reported the recommendations that were passed at the meeting. The proceedings have since been compiled and edited by F. Delange, J. T. Dunn, and D. Glinoer, and published by Plenum Press in cooperation with the NATO Scientific Affairs Division.

The present report abstracts items of particular interest. It does not include topics and countries covered in recent Newsletter articles.

Iodine and its Role in Humans

Requirements of Iodine in Humans, by F. Delange, University of Brussels.

This paper discussed the history and experimental basis for various recommended dietary allowances for iodine at different stages of life. It reviewed recommendations by the US National Academy of Sciences, published in 1989, and suggested modifications based on experimental evidence gained from considerations of iodine intake, excretion, and retention in full-term and pre-term infants. The author agreed with the US Academy recommendations for the following groups: children age 4-6, 90 mg/day; children 7-10, 120 mg; adolescents and adults, 150 mg; lactating women, 200 mg. He recommended increasing the US recommendation for infants 0-6 months of age, from 40 mg/day to 90; for infants 6 months to 1 year of age, from 50 to 90 mg; children age 1-3, from 70 to 90 mg; and pregnant women from 175 to 200 mg. Practical implications of these changes are that the amount of iodine in infant formula milk should be increased from the current 5 mg/dl to 10 or even 20 mg, and that pregnant and lactating women should receive iodine.

Sources of Dietary Iodine in Industrialized Countries, by J. T. Dunn, University of Virginia, Charlottesville, VA, USA.

This paper reviewed dietary iodine sources, particularly for the United States. It drew heavily on periodic market basket surveys by the US Food and Drug Administration, published in the Journal of the American Dietetics Association in 1981 and 1991. Total iodine intakes, calculated on this basis, were 180 mg/day for infants less than 1 year, 280 mg for 2 year olds, 340 mg for adolescent females, and 260 mg for women 30-35 years. Dairy and grain products accounted for over half of the iodine consumed, with a steady shift from dairy to grain sources with aging. These values represent a decrease from those of a similar survey a decade before, and were attributed to a decrease in the use of iodinated food coloring, particularly in breakfast cereals. The iodine content of milk comes from animal feeds, iodine-containing medications administered to cows, and iodophors for cleaning udders. The iodine from bread and cereals is added principally during food processing, such as iodate for stabilizing bread and erythrosine for food coloring. Other important sources of iodine in the developed country diet include iodized salt, vitamin and mineral preparations, kelp and other health foods, medicines, and medical products. The limitations of the market basket analysis were emphasized, but it still represents a convenient measure for tracking the iodine contents of foods. Changes in food processing undertaken for commercial considerations, such as the use of iodate in baking, can have major effects on iodine consumption patterns. This situation underscores the importance of regular monitoring for iodine intake by techniques such as newborn screening, goiter surveys, and urinary iodines.

In another part of the book, a paper by S. Pino and L. E. Braverman mentioned that the National Health and Nutrition Examination Survey III the United States, from 1990-1992, is showing a mean urinary iodine excretion of 165 mg/l, somewhat lower than values that were reported between 1973 and 1985.

Goitrogenesis in Iodine Deficiency, by U. Bürgi, H. Gerber, and H. Studer, University Clinic of Medicine, Berne, Switzerland.

This paper reviewed factors stimulating growth in the thyroid, and their relation to iodine deficiency. It traced the pattern of goiter production at different ages, from hyperplasia in young children through later colloid goiter to the heterogeneous thyroids of older patients. This pattern is the same as that found in simple goiter in iodine-sufficient areas. TSH is certainly a major growth factor. The authors note, as have many before them, that serum TSH levels are usually within the normal range in iodine-deficient populations, although the mean TSH may be higher than in iodine-sufficient populations, particularly for young children. Other growth factors have been suggested, including epidermal growth factor, insulin-like growth factor, transforming growth factor beta, and thyroid growth stimulating immunoglobulins. Their roles, if any, are not clear.

In the discussion Dr. Pinchera noted that he had not found evidence for thyroid stimulating antibodies in areas of endemic goiter either in Italy or Peru, and also could not find antibodies blocking the effects of TSH in severely cretinous subjects from those areas.

Selenium, Iodine, and the Thyroid, by J. P. Chanoine, J. L. Leonard, and L. E. Braverman, University of Massachusetts, Worcester, MA, USA.

Selenium has attracted the attention of thyroidologists during the last decade, because the type I deiodonase, which converts thyroxine to triiodothyronine in the liver, kidneys, and thyroids, is a selenoenzyme. The type II enzyme, which converts T4 to T3 in the pituitary, does not contain selenium.

Selenium deficiency is associated with Keshan disease, causing congestive heart failure, and Kashin-Beck disease, associated with degeneration of cartilage. In several studies, combined iodine and selenium deficiencies appear associated with a myxedematous form of endemic cretinism, but this relationship has not been firmly established nor a mechanism provided.

The authors provide a map of serum selenium concentrations by country in Europe, ranging from 50-100 mg/l. The daily selenium intake in Europe is 30-60 mg.

Iodine in the Food Chain, by M. Anke, B. Groppel, K-H. Bauch, Friedrich-Schiller-University, Jena, Germany.

Both geological origin of the soil and its distance from the ocean influence the iodine content of plants. For example, if plants growing on alluvial deposits are arbitrarily given a relative figure of 100% for their iodine content, boulder clay is 94%, slate 73%, new red sandstone 71%, and granite 54%. Glacial effects reduced the iodine content of central Europe. The lowest iodine content is in the red sandstone and granite sites forming large areas of Thuringiaw and Saxony.

Iodine is not thought essential for plants. Cereal seeds and flour contain the least amounts of iodine: for example wheat grain has a mean iodine content of 15 mg/kg dry matter, compared to potatoes with 82 mg/kg and white cabbage with 90 mg/kg. Leafy vegetables such as beets may have levels as high as 200 mg/kg, but some of this may be contamination from soils, which may contain 3 mg/kg.

The iodine status of domestic animals will reflect the land they forage on, which is iodine-deficient in much of central Europe. Control studies of iodine supplements as part of mineral mixtures for domestic animals show dramatic increases in the iodine content of milk.

This paper also reported on fecal as well as urinary iodine and found it to be 39% of the total iodine excreted, for an average of 16 mg/day compared to 25 mg/day in urine. In the discussion of this paper, Koutras reported studies showing a fecal excretion of 5-6 mg/day in low iodine conditions, and about 30 mg/day after iodine supplementation.

Feto-Maternal Thyroid Hormone Relationships in Iodine Deficiency: An Experimental Approach, by G. Morreale de Escobar, M. J. Obregón, R. Calvo, F. Escobar del Rey, Instituto de Investigaciones Biomédicas del C.S.I.C., Madrid, Spain.

This paper reported further progress in the extensive investigation of the iodine-deficient rat, as a model for iodine deficiency in humans, with particular regard to fetal maternal relationships. Because both mother and fetus have iodine deficiency, the developing fetus has low thyroxine levels throughout its development. The importance of maternal thyroid hormone during the early stages of pregnancy was stressed, with its possible implications for understanding neurological endemic cretinism in humans. The authors propose that the different degrees of central nervous system damage in iodine deficiency are causally linked to the different degrees of maternal hypothyroxinemia in different endemias.

Thyroid Regulation During Pregnancy, by D. Glinoer, University Libre de Brussels, Brussels, Belgium.

This paper reviewed the effects of low iodine intake in Belgium during pregnancy, and the effects of its correction. During pregnancy some iodine is "lost" by the mother to the fetus, and pregnancy increases renal clearance of iodide. These two factors increase maternal iodine requirements. Studies on healthy pregnant women in Brussels showed that the median iodine excretion during early pregnancy was about 50 mg/day, but later in pregnancy it decreased to about 40 per day. Several markers reflected these increasing demands: decreased serum thyroxine levels, increased T3 to T4 ratio, elevated TSH levels, increased serum thyroglobulin, and increased thyroid volume by ultrasonography.

The authors then investigated women divided early in pregnancy into three treatment groups: one received a placebo, the next a supplement of 100 mg iodide per day, and the last received 100 mg of thyroxine plus 100 mg of iodide. Thyroid volume increased by only 10% in the last two groups compared to 35% in the placebo, and the serum thyroglobulin increased by 40% in the placebo, and 8% in the KI group, but decreased by 24% in the double treatment group. TSH increased by 151% in the placebo group, 57% in the KI group and 24% in the KI plus T4 group. The authors concluded that iodine treatment alone in these marginally iodine deficient subjects could correct iodine deficiency and prevent the goiter and most of the elevation in TSH and thyroglobulin seen in the placebo group. In response to a question in the discussion, Dr. Glinoer noted that recently some multivitamin formulations for pregnant women in Belgium now include iodine, a change from previous preparations.

Neonatal Thyroid Function in Iodine Deficiency, by F. Delange, P. Bourdoux, M. Laurence, L. Peneva, P. Walfish, H. Willgerodt, University of Brussels, Belgium; University of Cardiff, Wales; Research Institute of Pediatrics, Sofia, Bulgaria; Mount Sinai Hospital, Toronto, Canada; University of Leipzig, Germany.

This paper focussed on the newborn's hypersensitivity to iodine deficiency, relative to that of adults and older children. Transient primary hypothyroidism is about six times higher in Europe than in iodine-sufficient North America, reflecting Europe's borderline iodine deficiency. This syndrome includes a transiently elevated serum TSH and low serum total and free T4, persisting for at least several weeks. It is more common in preterm than in full term neonates. Iodine supplementation at 40 mg/day can prevent this transient hypothyroidism. When a cutoff for recall in neonatal screening programs of 50 mU/ml in serum TSH taken on day 5 is used, the recall rate will be below 0.2%, and usually below 0.1% if the median urinary iodine concentration in the community is above 5 mg/dl. When the urinary iodine drops to 2 mg/dl, the recall rate reaches 10%. Thyroids of infants dying shortly after birth of other causes, in three cities of differing iodine content (Toronto, estimated 600-800 mg/day in adults, Brussels, 51 mg, and Leipzig 16 mg) had iodine contents respectively of 292 mg, 81, and 43. The thyroids of the Leipzig infants weighed three times as much as those in Toronto or Brussels. A calculated iodine turnover was 17% per day for Toronto, 62% for Brussels, and 125% for Leipzig. Thus, the neonatal thyroid is particularly sensitive to the stress of iodine deficiency, and the perinatal period is also a time when proper brain development is critically dependent on adequate thyroid function, so this transient neonatal hypothyroidism poses a real risk to children in iodine-deficient countries.

Discussion of this paper showed that these has apparently been little long-term follow-up of transiently hypothyroid neonates. Dr. Vigneri of Catania described studying 13 infants from an iodine deficient area of Sicily, who had transient hypothyroidism in the perinatal period, characterized by elevated serum TSH levels but normal serum T4's. On follow-up eight to ten years later, these children had mild thyroid enlargement but growth and intellectual ability appeared normal. The numbers were small, and do not remove the fear that transient neonatal hypothyroidism may impose significant long-range deficits.

Assessment and Treatment of Iodine Deficiency

Congenital Hypothyroid Screening Programs and the Sensitive Thyrotropin Assay: Strategies for the Surveillance of Iodine Deficiency Disorders,by D. Nordenberg, K. Sullivan, G. Maberly, V. Wiley, B. Wilcken, F. Bamforth, M. Jenkins, H. Hannon, B. Adam, Emory University School of Public Health, Atlanta, GA, USA.

This paper compared newborn screening with TSH on filter paper using a sensitive two-site fluoroimmunometric assay with mouse monoclonal antibodies to TSH in a direct sandwich technique, with the sensitivity of 1.4-2.0 mU/ml whole blood. Curves were drawn by day of life that the test was performed, from the first to the fifth day. TSH values were slightly higher on days 1 and 2. The median TSH in New South Wales ranged from 0.8-1.3 mU/ml and that for Alberta 1.3-3.5 mU/ml. Ninety-five percent of TSH values were below 5.7 mU/ml (New South Wales) and 10.9 mU/ml (Alberta) during the first day, 4.1 mU/ml and 6.3 mU/ml, respectively for day 2, and lower on subsequent days. (Both Alberta and New South Wales are iodine sufficient).

The authors note that screening programs for congenital hypothyroidism have typically used a TSH cut-off of 20-25 mU/l whole blood (about 40-50 mU/l serum), which is usually adequate for screening. However, areas with mild iodine deficiency may have slight elevations in TSH that would not be picked up in the screening cutoffs. Use of sensitive TSH assays is important for applying neonatal screening data to epidemiologic assessment of iodine deficiency.

National Program of Iodine Prophylaxis and Neonatal Thyroid Function, by V. Hesse, Childrens Clinic "Lindenhof", Berlin, Germany.

In parts of the former East Germany, the goiter prevalence in adolescents was as high as 46%. Neonatal goiter was common, and 50% of neonates with goiter had transient hypothyroidism as shown by subnormal serum thyroid hormone levels and elevated serum TSH values. Urinary iodine levels in East German adults were approximately 20-30 mg/day.

As described elsewhere, iodization programs began in the early 1980's, initially with salt iodization, 25 mg KI/kg, later shifted to 32 mg potassium iodate per kg, and later by addition of potassium iodate, 18 mg/kg, in mineral mixtures for pigs throughout the country and for cattle in the southern districts. Five years later goiter prevalences in newborns have decreased to < 1%, from previous levels up to 12.4%. For example, newborn goiter decreased in the city of Jena from 6% in 1978 to 0.1% in 1988, and only one newborn had goiter there in 1991. Newborn goiter required 445 days of hospitalization in 1978, but only 14 by 1986. The urinary iodine excretion of newborns in Jena increased from 10.6 mg/l in 1982 to 38.8 in 1991. The thyroid weight of newborns decreased from 9.0 to 1.6 g in Chemnitz. The recall rate in TSH screening decreased from 0.7% to < 0.1%.

Following German reunification in 1990, iodine prophylaxis became voluntary in the East, and the use of iodized salt in the household decreased from 84 to 20%. In East Berlin, the neonatal TSH increased following reunification, from 0.99 mU/ml to 1.76, the latter value similar to that in West Berlin. The authors attribute this change to the increased use of iodine-containing disinfectants in both West and East.

The authors emphasize, as have other commentators on the former East Germany, that introduction of iodine into animal feeds was the most successful measure in correcting human iodine deficiency.

In the discussion Dr. Hesse noted that inclusion of iodine in animal feeds led to a net gain for the agricultural industry of 200 million DM, from increased production of milk and meat. This financial point was very important in convincing national authorities of the need for animal iodine supplements.

Dietary Iodine Supply and Radioiodine Uptake: The Case for Generalized Iodine Prophylaxis, by A. M. Ermans, Hôpital Saint Pierre, Brussels, Belgium.

Of the world's 500 nuclear power units, over 1/3 are in Europe and 137 are in the European Community. Accidents at nuclear power plants can lead to fallout, particularly isotopes of iodine. Fallout from radioactive iodine can cause thyroid cancer, as documented in many reactor accidents over decades. Uptake of radioactive iodine by an individual thyroid is strongly dependent on the amount of stable (i.e., nonradioactive) iodine in the diet. Iodine-deficient subjects will have an increased uptake of radioiodine, and hence will be at more risk from fallout in the case of an accident. In this paper the author estimated the range of radioiodine uptakes in various European countries, from their reported mean urinary iodine excretion values. With this approach, Dr. Ermans estimated that Great Britain and Finland have uptakes less than 20%, Norway, Sweden, and Switzerland from 20-30%, Ireland, Holland, Denmark, Czechoslovakia, and Austria from 30-40%, and France, Germany, Italy, Spain, Greece, and Belgium have uptakes over 40%. In general, iodine prophylaxis should reduce the risk of thyroid irradiation by two to three fold. This point is important because of the large number of nuclear plants in Europe, their frequent location near cities with large populations, and recent experience with nuclear accidents, particularly Chernobyl.

Study of a System of Continuous Iodine Release into Water (RhodifuseR Iode), by E. Pichard, A. Blanchard, B. Debeugny, Bamako School of Medicine and Rhône-Poulenc Rorer Company, Antony, France.

This paper described results applying the Rhône-Poulenc RhodifuseR water iodization system. The basic unit of the RhodifuseR Iode system is a porous, polyethylene cylinder that can be controlled to release 2 mg of sodium iodide per hour. The number of units used depends on the hourly water flow of the well. For example, with a water flow of 600 liters per hour, five units will raise the concentration to 50 mg iodine per liter.

This paper reported a field study in three severely iodine-deficient villages in Mali. Before implementation, 72% of the urinary iodines were below 2.5 mg/dl, but one year later 94% were greater than 10. A control untreated village initially showed 68% below 2.5 mg/dl and no subsequent improvement. The total goiter rate in females had decreased from 64% to 42% by one year after installing the units, while the control population remained the same. At the concentrations used there was no change in taste, smell, or color of the water, and it was well accepted by the population.

Iodine Nutrition in Europe

Austria: Update on Iodine Nutrition, by G. Riccabona, Univ. Klinic für Nuklearmedizin, Innsbruck, Austria.

A recent issue of the IDD Newsletter (vol. 7, no. 4, November 1991) described IDD in Austria to that point. The present communication offers further information. Data from the Tyrol area in 1992 now show the mean urinary excretion to be 145 mg/g creatinine, up from 1980 values of 65.3. The goiter incidence in schoolchildren is now 5%, down from 12% in 1980. Salt purchased for household use is now 99% iodized, and all salt for animals is iodized. The estimated cost of iodization for the country is $70,000 per year, which is paid by the federal government. The use of iodized salt is almost mandatory, and the iodine content of salt is regularly monitored at the factory. There is no other regular source of iodine supplementation in the country. The incidence of congenital hypothyroidism is 1:5153, consistent with iodine sufficiency.

The mean thyroid volume in schoolchildren from the second to fourth grade (approximately 8-10 years old), was 3.23 ± 1.19 ml in the second grade, and 4.07 ± 1.42 in the fourth grade. Observations in a thyroid clinic show a slight increase in Hashimoto's disease, a significant decrease in toxic adenoma and constant rates for thyroid cancer.

Belgium: Status of Iodine Nutrition and Thyroid Function, by C. Beckers, A. Ermans, P. de Nayer, F. Delange, D. Glinoer, and P. Bourdoux, Universities of Louvain and Brussels, Belgium.

Studies in the last 30 years have indicated a goiter prevalence in schoolchildren, age 6-16, extending from 2% in the western part of the country to 10% in the east. The median 24 hour excretion in 1990 was reported as 50 mg iodine, 59.3 and 50 in three studies. The urinary iodine concentration averaged 5.3 ± 4.3 mg/dl and in another study was 5.6. Seventy-six percent of values were below 10 mg iodine/dl, 47% below 5, and 15% below 2. A study of 196 infants from Brussels showed a median urinary iodine excretion of 4.8 mg/dl, and 53% of the values were below 5. The recall rate of neonates, using a TSH level of 50 mU/ml, was 0.2% in Belgium, compared with 0.1% in Sweden where the iodine intake is higher. Eighty-five percent of pregnant women in the Brussels area had a daily urinary iodine excretion below 100 mg. Breast milk concentrations showed a median iodine concentration of 5.4 mg/dl, in one study, and 9.1 in another.

The authors conclude that Belgium has marginally low iodine intake and recommend that it be increased. There is no government program for salt iodization.

Bulgaria: Status of Iodine Nutrition, by L. Peneva, B. Lozanov, and D. Koev, University of Medicine, Sofia, Bulgaria.

A 1957 survey found a goiter prevalence of 19% in schoolchildren for the whole country, with 12 endemic regions in the southwest having a prevalence of 55.9%, and some areas having 3.5% cretins. Mandatory iodine supplementation was introduced in 1958, with 20 mg KI/kg in the 12 endemic regions. In addition, tablets of 1 mg KI were given to schoolchildren and to pregnant and lactating women. Follow-up in 1974 in these provinces showed that the goiter prevalence had decreased to 12%. However, control since then decreased, and the goiter prevalence in 1989 was back to 23.3%.

A national survey of schoolchildren for the whole country showed a prevalence of 4.3% in 1988, reaching 19.8% in 6-15 year olds in the endemic regions. A study in 1991 of Vratza in the Balkan mountains showed an average urinary iodine excretion of 5.7 mg/dl, with a goiter rate of 15%; in another region, Razlog, between the Pirin and the Rila mountains, urinary iodine excretion was only 2 mg/dl, and the goiter rate was 61%.

Currently salt iodized with KI at 20 mg/kg, partly imported, partly produced in Bulgaria, is mandatory in these 12 endemic areas. It is available and not more expensive, but its iodine content is not monitored regularly. The program of supplementation with KI tablets is still in effect, but not carried out regularly.

A national IDD program was proposed in September 1991. Its major points include: (1) monitoring of urinary iodine in representative groups; (2) increasing the iodine content of salt to 32 mg/kg, using potassium iodate and regular monitoring its content; (3) additional iodine supplement for risk groups and for domestic animals; (4) search for goitrogenic substances, such as nitrates and thiol carbonates; (4) follow-up surveys for IDD status; (5) introduction of neonatal thyroid screening; (6) increased public awareness for IDD in Bulgaria; and (7) financial support for the import and production of iodized salt. Management of the program is assigned to the National Standing Committee for the Control of IDD to the Ministry of Health. However, funding is currently insufficient, and support is needed.

Commonwealth of Independent States (CIS): Iodine Deficiency Disorders and Endemic Goiter, by G. Gerasimov, O. Judenitch, and I. Dedov, Russian Endocrinology Research Centre, Moscow, Russia.

A recent issue of the IDD Newsletter (vol. 8, no. 1, February 1992) gave detailed information about IDD in parts of the former Soviet Union. The present paper described efforts in the middle part of this century with compulsory iodine prophylaxis, resulting in considerable decrease in goiter prevalence. However, the prevention program and monitoring were discontinued in 1970.

A questionnaire survey in 1990 in 11 of the 15 former Soviet republics recorded slightly over one million persons with detectable goiter, a marked increase over 1969. Spot surveys by Gerasimov and Gutekunst in 1991, using ultrasound technology, showed goiter prevalences of 12% in St. Petersburg, 24% in Yasnogorsk, and 24-33% in the Tula region; palpation studies in Brjansk estimated goiter prevalence as about 40%. The median urinary iodine excretion in Tula was 9.0 mg/dl, the mean TSH was 1.54. There have not been systematic national surveys in recent years.

In 1990 the former USSR produced 3.5 million tons of salt, 2.7 million for household use, of which 794,000 tons were iodized with KI. The official level is 25 grams iodine/ton salt. It is packaged and goes directly to the consumer, but spot checks show its actual iodine content to be low: it was adequate in only 50% of samples from Kazachstan, 10% from Belorus, and 3% in Azerbajdzan. In 1990 nine producers iodized salt. The largest salt producers are in Russia and Ukraine, with mines and factories also in Kazachstan, Turkmenistan, Tadzikistan, Armenia, and Belorussia. The CIS produces its own iodine in satisfactory amounts. Tablets containing 100 mg iodine are used for supplementation in some programs for children and pregnant women, particularly in Gomel and Belorus, which drew international attention from effects of the Chernobyl disaster. In 1991, 550,000 Lipiodol capsules were distributed by UNICEF to children in iodine-deficient areas exposed to radioiodine from the Chernobyl accident.

Currently there is no national program, and IDD control takes place at regional endocrinology (anti-goiter) dispensaries. In the several regions where iodine tablets are given, such as North Caucasus, Altaj and Belorus, these are provided from local funds. The local sanitary stations are responsible for monitoring iodine content of salt, but this is rarely carried out in practice.

The authors note that while iodine deficiency is mild in many places, it may be much more severe in more remote parts of the region. They recommend rapid assessment, development of a plan of action, and an effective iodization campaign.

Croatia: Endemic Goiter, by Z. Kusic, N. Dakovic, et al., University Hospital, Zagreb, Croatia.

(A previous report on endemic goiter in the former Yugoslavia appeared in the IDD Newsletter (vol. 8, no. 1, February 1992); the current report provides additional information.)

Recent schoolchildren surveys show an overall goiter prevalence in Zagreb of 19% with a median urinary iodine excretion of 9.0 mg/dl. Thyroid volume by ultrasound in age 7-11 was 8.2 ml, in 12-15 year old girls 11.6 ml, and in 12-15 year old boys 10.6 ml. In the village of Rude the goiter prevalence was 35% with a median urinary iodine excretion of 7.4 mg/dl. In Dakovo the goiter prevalence was 22%, in Rijeka, 13%, and in Split 8%.

Denmark: Iodine Intake - Influence on the Pattern of Thyroid Disease, by P. Laurberg, K. M. Pedersen, and S. B. Nohr, Aalborg Hospital, Aalborg, Denmark.

A 1969 survey of adolescent males showed a general urinary iodine excretion of 64 mg/day, with lows around 40. A large unpublished survey of schoolchildren found only a few cases of goiter, and supplementation was regarded as unnecessary.

Several studies of urinary iodine in the last two decades gave averages ranging from 73 to 100 mg iodine per 24 hours. It was pointed out that vitamin tablets are popular in Denmark, and many of them contain 150 mg iodine. A study of subjects not taking vitamins or similar sources of iodine had median urinary iodine excretions of 36 mg/g creatinine in a morning spot urine. Thus, subjects not taking such supplements have low urinary iodines. A comparative study with iodine-sufficient Iceland showed that the incidence of toxic nodular goiter was higher in Denmark. Studies on pregnant women in Randers showed a median 24 hour urinary excretion of 57 mg, and 54 mg in nonpregnant controls. Studies in several other hospitals showed that only 1/3 of pregnant women take iodine in the form of vitamin/mineral tablets. In those not taking such supplementation, median urinary iodines ranged from 28 to 62 mg/g creatinine. Milk iodine was also low, the median ranging from 22- 55 mg/l. The authors recommended that all women should receive iodine supplementation during pregnancy and lactation, and salt iodization should be considered for the general population.

Finland: Present State of Endemic Goiter, by B. A. Lamberg, K. Liewendahl, and M. Välimäki, University of Helsinki, University Cent Hospital, Helsinki, Finland.

Endemic goiter was common in the early part of this century. Goiter was also a problem in domestic animals. For the last 25 years table salt has contained 25 mg KI/kg, and over 90% of the total salt for human consumption is iodized. Prophylaxis was intensified in the 1970's, and the mean iodine intake has been about 300 mg/day for the last 12 years.

Recent data include an incidence of congenital hypothyroidism in Finland of 1 in 3500, a decrease in goiter prevalence to less than 5%, a decrease in normal 24 hour radioiodine uptake from 60 to 70% at 24 hours in the 1950's, to 22% in 1979. Thyroid size at autopsy has decreased, and recent estimates by ultrasound have found volumes comparable to countries with iodine sufficiency.

In the 1950's about 50% of iodine intake came from milk and milk products and about 20% from iodized salt. At that time cow's milk contained 27 mg iodine per liter, but this had increased to 170 mg/l by the end of the 1970's. Total daily human intake exceeded 300 mg/day, of which close to 200 mg/day is derived from milk, milk products and hen's eggs. Only 20% came from iodized salt because salt consumption had decreased from 7-8 g/day in the early 1960's to the current 4 grams or less. More recent studies show that the iodine concentration of milk has remained about the same. The iodine content of hen's eggs has decreased by about 50%. Thus, the intake remains about 300 mg/day. Recent studies of radioiodine uptakes show the average 24 hour to be at 29-32%. The incidence of nodular goiter as a cause for hyperthyroidism has decreased from 92% in the 1930's to about 16% recently.

These data show that Finland is apparently iodine sufficient, mostly from dietary factors other than iodized salt.

France: Goiter Prevalence and Salt Iodization, by R. Mornex, M. Boucherat, M. Lamand, J. C. Tressol, and C. Jaffiol, Faculty of Medicine A. Carrel, Lyon, France; Unité Maladies Nutritionnelles, INRA, Theix, France; and Hôpitaux de Montpellier, Montpellier, France.

A 1984 study by the French Society of Endocrinology, abstracted in a previous IDD Newsletter, described a prevalence of thyroid hypertrophy of 16.7% and a mean urinary iodine excretion of 85.2 mg/g creatinine. Follow-up urinary iodine in several districts showed a mean increase of about 50% in one test site with a previous low excretion, but did not change in another that was also measured.

Commercial salt is iodized either as fine or coarse. Values in 1986 showed that the fine contained 3.3 mg/kg iodized, and the coarse contained 14.5; in 1992 these values were respectively, 7.5 and 9.6.

The authors note that endemic goiter still persisted in 1986, but that the iodine content of salt may have increased recently. With a mean iodine content of 7.5 mg/kg, daily supplementation from this source would be about 25 mg of iodine per day. They note the need for further survey of iodine intake in France.

Germany: Iodine Deficiency Diseases and Interdisciplinary Iodine Prophylaxis Before and After Reunification, by K. Bauch, M. Anke, W. Seitz, St. Förster, V. Hesse, G. Knappe, R. Gutekunst, J. Kibbassa, J. Beckert, Clinic for Internal Medicine, Klinikum Flemmingstraße, Chemnitz, Germany.

Widespread endemic goiter was apparent from several surveys in the 1970's and 80's, particularly in the southern provinces. Damaging effects of iodine deficiency in domestic animals had also been recognized. In 1985 an interdisciplinary iodine commission was established, including representatives from human medicine, veterinary medicine, agricultural production, the animal feed industry, the ministry of health, and the salt industry. Beginning in 1984, 84% of salt for human consumption was iodized, and since 1986 iodine containing minerals were fed to farm animals. The average urinary iodine excretion in adolescents in Chemnitz increased from 27.7 mg/iodine/g creatinine in 1985 to 69 mg/iodine/g creatinine in 1990. The authors note that 70% of the daily consumed salt comes from commercial food stuffs. Bread products account for 40% of daily salt consumption. The authors note that with German reunification, iodized salt use became voluntary and the country needs to promote iodized salt in the food industry.

Greece: Iodine Nutrition and Iodine Deficiency Disorders - Signs of Improvement, by D. A. Koutras, G. Piperingos, J. Mantzos, M. Boukis, K. S. Karaiskos, and S. Hadjiioannou, Athens University, Department of Clinical Therapeutics, Athens, Greece.

Surveys in the 1960's established the presence of endemic goiter in the western part of the country, particularly the Pindos Mountain ranges and extending into Albania. Other areas include the Olympus Mountains, mountainous areas in central Greece and some large islands, including Crete. Endemic cretinism has not been found, but newborn TSH levels were higher in the endemic areas than in the non-endemic ones. The early studies showed urinary iodine levels ranging from 17 to 38 mg excreted per day, and goiter rates in the 20% range, higher in women. Sporadic intervention with iodized salt and iodized oil injections occurred, but were not sustained. After some initial administrative tangles, iodized salt has become available and is sold on a voluntary basis, but its iodine content is frequently below standard, and its price is higher than non-iodized salt.

Despite these difficulties, recent data from 1987 to 1992 show a general decrease in goiter prevalence and an increase in urinary iodine levels. Data from 15 different areas of Greece showed most to have urinary iodines above 100 mg/l and goiter prevalence below 10%. Exceptions were Regini in central Greece with a goiter prevalence of 18%, and Athamanio, Pramanta, and Christi in Epirus, all with goiter prevalences around 20 and urinary iodines around 35 mg/l. In Athens urinary iodine excretion has increased from 45 mg/day in 1964 and 94 mg/g creatinine in 1980 to a present 208 mg/g creatinine. These increases are attributed to better transportation, with more consumption of iodine-containing foods than occurred a generation ago when most food sources were local.

Hungary: Status of Iodine Nutrition, by F. Péter, Buda Children's Hospital, Budapest, Hungary.

A recent issue of the IDD Newsletter (vol. 8, no. 4, November 1992), described some aspects of IDD in Hungary. The 1989/90 survey reported a 5.8% prevalence overall and suggested a general decrease from previous surveys. The iodine content of table salt was increased to 20 mg/kg in 1976, and recently KIO3 has been used instead of KI. Breast milk in Budapest contained an average of 4.2 mg iodine/dl. The thyroid volumes of 1081 healthy children in Budapest were found by ultrasonography to be significantly higher than those in iodine sufficient regions. The 24 hour radioiodine uptake in normal adults reached 40%; the incidence of congenital hypothyroidism in neonatal screening was 1:4500. Iodized salt is available at a reduced price and is regularly monitored. One factory produces iodized salt in Hungary, but most is imported. A national committee and program for IDD are currently being prepared.

Ireland: Status of Iodine Deficiency, by A. M. Hetherton and P. P. A. Smyth, University College Dublin, Dublin, Ireland.

Data in 1988 showed a mean urinary iodine excretion of 118 ± 82 mg/g creatinine, median 96. The mean 24 hour 131I uptake had decreased from 48% in the mid-1960's to 38% in the 1980's. In the present study, 2740 urine samples from various parts of Ireland showed a mean iodine content of 108 mg/g creatinine, and a median of 82, but 22% of individual values were below 50. The iodine content of milk showed wide variation by season, from a median of 50 mg/l in summer to 79 in winter. Urinary iodine values in schoolchildren paralleled these changes. Mean values of thyroid volume in females were 12.2 ml and 15.6 ml in males; 8.2% of women and 2.6% of men had significant enlargement. Thyroids enlarged up to 50% in pregnancy, compared with nonpregnant controls. These results showed Ireland to have moderate iodine deficiency.

Italy: Iodine Deficiency Disorders - Current Status, by F. Aghini-Lombardi, L. Antonangeli, T. Rago, P. Vitti, A. Pinchera. Istituto di Endocrinologia, Università degli Studi di Pisa, Pisa, Italy.

Local and transient iodine prophylaxis programs have been tried over the past 30 and 40 years. The manufacture of iodized salt was permitted by law in 1972, and it was distributed by request to certain endemic areas. In 1977 distribution was extended to the whole country. In 1991 the amount of iodine was raised from 15 to 30 mg/kg by a Public Ministry Decree and potassium iodate was permitted as an alternative to potassium iodide.

Epidemiology - Data reported from several groups are shown in Table 1. The total number of schoolchildren (6-14 years) examined is 71,112 in the years from 1978 to 1991, including 5,046 controls residing in urban areas and 66,066 subjects residing in endemic areas. Surveys were performed throughout Italy in predominantly hilly and mountainous districts known or suspected to be endemic. With a few exceptions, the mean urinary iodine excretion in endemic areas was below 75 mg/g creatinine and, in several instances, below 50 mg/g creatinine.

Most of the high iodine values were found in surveys carried out in the last 2-4 years. In non-endemic urban areas urinary iodine excretion varied from 85 to 175 mg/g creatinine, greater values being found in samples collected during the past two years. The prevalence of goiter in schoolchildren of endemic areas varied widely, ranging from 14% to 73% and was roughly correlated inversely with iodine excretion. In general, the prevalence of goiter was greater in central and southern Italy than in the north, in contrast to the traditional concept that endemic areas were chiefly in the Alps region. The affected areas are principally non-urban and mountainous. In the mildly affected districts only a minority of the schoolchildren had large and/or nodular goiters, the majority having grade 1A or 1B, according to the WHO criteria. In the same areas many adults had multinodular goiter, reflecting longstanding iodine deficiency. In the control areas (5,046 subjects) the prevalence of goiter was below 10% with the exception of 15% in Reggio Calabria, the latter perhaps attributable to recent massive immigration from rural or adjacent districts.

In general, surveys in the past two to three years have shown a lower prevalence of goiter than that observed earlier in the same area or in adjacent areas with similar geographical and socioeconomic characteristics. This finding cannot be attributed to formal prophylaxis with iodized salt, but may be explained by improved socioeconomic conditions and a more effective trade and communication system (silent prophylaxis). In some of the limited areas where iodine prophylaxis was introduced, a striking reduction of the prevalence of goiter was documented. For example, the introduction of iodized salt in Garfagnana (Toscana) led to an increase in mean urinary iodine excretion from 47 ± 22 to 130 ± 73 mg/g creatinine and a reduction in goiter prevalence from 60% to 9% in schoolchildren.

Thyroidal status - Table 2 lists mean values for serum thyroxine (T4), triiodothyronine (T3, thyrotropin (TSH), thyroglobulin (Tg) and urinary iodine excretion (UI) in 3,089 schoolchildren and 2,212 adults from iodine deficient areas of Toscana and in an iodine-sufficient control group. On comparison with the controls, the iodine-deficient showed normal mean serum concentrations of T4, T3, and TSH, although the T3 concentration was slightly but not significantly elevated relative to controls, and a significantly higher mean serum Tg concentration. In the adults goiter size was positively correlated with serum Tg values and inversely correlated with serum TSH, perhaps suggesting the development of autonomy. No correlation was found between urinary iodine excretion and goiter size. Similar results were obtained in Sicilia, Calabria, Trentino Alto Adige and Campania.

In the adult population the frequency of thyroid autoantibodies (16.5%) was significantly higher than in the control group (8.1%) and was not related to the presence of goiter, although more frequently detected in patients with a large goiter. Goiter in children residing in the iodine deficient area was not related to the presence of thyroid autoantibodies in their parents (5-6). These data suggest that thyroid autoimmune phenomena do not play an important role in goitrogenesis, but may occur in endemic goiter rather as a consequence of the iodine deficiency disorders. On the other hand, the finding that goiter was more frequently present in the offspring of goitrous parents (p < 0.005), suggests a possible role of hereditary factors.

Unrelated studies by Ermans et al., showed the 24 hours thyroid radioactive iodine uptake (RAIU) in an endemic area of Sicilia to be 40-70%, inversely correlated with the urinary iodine excretion.

Neonatal screening - The incidence of congenital hypothyroidism in a screening program covering 94% of the newborns in Italy was 1/2813 in 1991. This frequency is similar to those observed elsewhere in Europe but much greater than in iodine sufficient countries such as the USA and Japan. Indirect evidence suggests that the iodine deficiency accounts for this difference, but this hypothesis is not proven. More newborns from areas of iodine deficiency in Sicilia had elevated TSH's and low T4's than in control areas. These changes were transient in most cases, but persisted at the recall examination in some infants.

Neonatal defects - Cretinism has been found in some areas with moderate or severe iodine deficiency (urinary iodine below 50 mg/g creatinine). In a study performed in 1981 in Sicilia, 19 subjects with mental defects were identified in an endemic area with a mean urinary iodine excretion < 43 mg/day and a goiter prevalence in schoolchildren of 42-68%. The area population was 37,080 people, so that a cretinism prevalence of at least 0.5 per 1,000 individuals could be estimated. More recently, 22 cases of myxedematous and/or neurological cretins were identified in an area of central Italy with a mean urinary iodine excretion of 40 mg/g creatinine and a schoolchildren goiter prevalence of 51%; all were older than 35 years. Minor neuropsychological impairment was detected in schoolchildren in areas with moderate iodine deficiency in Toscana and Sicilia, including subtle but significant defects in information vocabulary and in coding subtests.

Iodized salt - Iodine is supplemented by addition to salt for domestic use. Iodized salt may be distributed and traded all over the country but its use is not mandatory. Currently only 2% of Italy's total salt for domestic consumption is iodized, a failure attributable mainly to a lack of adequate information dissemination to the general population and a consequent decrease in demand and lack of availability of iodized salt at the local level.

So far, satisfactory large scale iodine prophylaxis has been achieved only in Provincia Autonoma di Bolzano (Alto Adige), where more than 50% of the population uses iodized salt and the goiter prevalence has decreased from 22.2% to 2.4%. On a smaller scale, a local iodine prophylaxis program has been successful in the above mentioned endemic area of Toscana.

As a general trend, urinary iodine levels have increased and goiter prevalence has decreased in recent surveys relative to results anticipated from earlier studies in comparable adjacent areas. This finding, in the absence of a formal prophylaxis program by iodized salt, is probably due to a more effective trade and communication system (silent prophylaxis). However, IDD prevention should rely on formal and organized iodine prophylaxis rather than on unpredictable and uncontrollable factors that do not uniformly reach the more affected areas.

At the national level, it has been estimated that the total cost per year for diagnosis and treatment of endemic goiter in 1985 amounted to at least 255 billion lire (approximately US $160 million), which represented 0.4% of the total Public Health Ministry budget. In contrast, conducting an effective national information campaign about the iodine deficiency disorders and their eradication would cost only a tiny fraction of that amount (2-3 billion lire). Thus, effective iodine prophylaxis would be worthwhile solely on a cost benefit basis.

Conclusions - Mild to moderate iodine deficiency continues throughout Italy, mostly in rural areas. Marginally low iodine intake occurs in several districts including urban areas. Iodized salt is available but is consumed by only a small fraction of the population. Silent prophylaxis has had some effect so far but cannot be regarded as a satisfactory solution for the problem. In the absence of mandatory iodized salt for consumption, appropriate and effective measures should be enacted by health authorities to ensure adequate information to the general population.

Table 1. Prevalence of goiter and urinary iodine excretion in some Italian regions.

Area Number of Prevalence of Urinary iodine
of study subjects Goiter ug/g cr ug/l
Endemic areas
Trentino 3,109 24 10 -
Friuli 2,052 37-59 85-122 -
Veneto 1,940 15 125 -
Emilia-R. 10,912 21-69 45-110 -
Toscana 7,774 22-59 35-97 -
Marche 6,156 17-41 54-84 -
Campania 5,742 21-73 60 35
Abruzzo 1,237 47-60 64
Molise 1,800 14 - -
Basilicata 177 55 46 -
Puglia 2,179 48 38 -
Calabria 10,654 22-57 80 58
Sicilia 8,977 41-67 - 19-76
Sardegna 3,357 19-40 66-105 -
Control Areas - - - -
Toscana 317 6-7 88-175 -
Marche 1,285 8 165 -
Campania 436 < 10 85 -
Sardegna 657 10 105 -
Sicilia 1,867 2.2-6.6 88-114 -

Total number of subjects examined: endemic areas 66,066; control areas 5,046.

Table 2. Serum thyroid hormones, TSH, thyroglobulin, and urinary iodine excretion from endemic and control areas of Tuscany.

Area TT4 TT3 TSH Tg UI
(ug/dl) (ng/dl) (uU/ml) (mg/ml) (ug/g cr)
Endemic areas
Adults (2,212)* 8.7 ± 0.2 191 ± 2.9 2.3 ± 0.2 40.2 ± 3.1** -
Schoolchildren (3,089)* 8.7 ± 0.2 189 ± 3.1 1.8 ± 1.3 60.8 ± 8.3** 42.0
Control areas
Adults (355)* 7.5 ± 0.7 151 ± 1.3 1.7 ± 0.2 9.5 ± 0.9 -
Schoolchildren (212)* 8.3 ± 0.6 168 ± 3.0 1.8 ± 0.3 16.8 ± 1.1 87.0
Adults (2,212)* 8.7 ± 0.2 191 ± 2.9 2.3 ± 0.2 40.2 ± 3.1** -

Netherlands: Iodine and Goiter - A Role for Nitrate Pollution?by D. van der Heide and J. P. Schröder-van der Elst, Department of Human and Animal Physiology, Agricultural University, Wageningen, The Netherlands and Department of Endocrinology, University Hospital, Leiden, The Netherlands.

A law in 1968 required that bakers use salt in bread containing 48 mg KI per kg. Iodized salt, 3-8 mg KI/kg, had been available since 1928, but was withdrawn in 1974. Because urinary iodine excretion was still low, the government in 1982 re-introduced table salt containing 23-29 mg KI/kg and increased the iodine content of bread salt to 60 mg KI/kg. Several recent studies from 1987 and 1992 show that over 60% of women and about 35% of men excrete less than 100 mg iodine per 24 hours. The total goiter rate was 35% for women and 18% for men. The authors commented on the possible effects of nitrates used in agriculture. They found a significant correlation between low urinary iodine excretion in women and high excretions of nitrate.

Norway: Urinary Excretion of Iodine, by H. Frey, B. Rosenlund, K. Try, and L. Theodorsen, Aker University Hospital and The Norwegian Radium Hospital, Oslo, Norway.

Studies in 1972 and 1985 showed that urinary iodine excretion is adequate. Median values are around 200 mg iodine per 24 hours. Norway has salt iodized with KI, but only at 5 ppm. Both iodized and non-iodized salt are available in the market at the same price. A comparison of 10 males using iodized table salt and 10 not using it showed little difference in mean 24 hour urinary iodine excretion (221 mg vs. 207). In 1950 the Department of Agriculture required the addition of 2 mg/kg of iodine, in the form of KIO3, to cattle fodder, because goiter had occasionally been found in Norwegian cattle. In 1972 the median iodine content of cow's milk was 66 mg/l in summer and 127 in winter. Saltwater fish are heavily consumed in Norway, particularly on the coast. Mean 24 hour urine iodine excretions of Norwegians eating salt fish was 289 mg iodine, compared to 127 in Norwegians not eating salt fish. Vitamin and mineral preparations labeled as food additives, to satisfy minimal daily requirements, are required to contain between 40 and 225 mg iodine per daily dose. Some seaweed products containing large amounts of iodine are consumed, and have occasionally produced iodine goiter and Jod-Basedow. The authors conclude that iodine deficiency is no longer a problem in Norway.

Portugal: Endemic Goiter, by L. G. Sobrinho and A. L. Oliveira, Department of Endocrinology, Portuguese Cancer Institute, Lisboa-Codex, Portugal.

Endemic goiter was recognized in east central Portugal for many years, and in the 1970's one region in this area received prophylaxis with iodized salt. Salt enriched with potassium iodate, 20 mg/kg, is mandatory in this region, but is not allowed in the rest of the country.

The authors surveyed the country over the years 1980-89, dividing the country into 178 areas, but omitting the heavily populated coastal region. They assessed 31,000 primary schoolchildren, 18,000 secondary students, and 786 adults, and obtained random urine samples from 1/10th of the children studied. They found that most regions, including the one receiving iodized salt, no longer had endemic goiter, but some regions had more than 10% goiter, and some greater than 30%; these areas were principally in the eastern, central, and southern parts of the country. In 61 of the 178 areas the median urinary iodine excretion was below 50 mg iodine/g creatinine, with ranges among the regions from 12-129 mg iodine/g. A median for Lisbon schoolchildren was 71 mg iodine/g creatinine, and a 1991 study of adults in Lisbon showed a median of 46 mg iodine/g creatinine. The goiter prevalence correlated inversely with urinary iodine excretion, positively with schistous soil and negatively with clay soil.

The authors concluded that endemic goiter is still active in Portugal, and that overall iodine deficiency persists.

Romania: The Status of Iodine Nutrition, by M. Simescu, R. Popescu, D. Ionitiu, E. Zbranca, E. Grecu, E. Marinescu, L. Tintea, E. Nicolaescu, M. Purice, M. Popa, and R. Gutekunst, Institute of Endocrinology, Bucharest, Romania.

Endemic goiter was recognized at least a half century ago, iodized salt prophylaxis was started in 1948, and relevant legislation was promulgated in 1956. The latter mandated iodized salt in 23 districts. Potassium iodide tablets were also ordered. A large country-wide survey was carried out between 1978 and 1980 in 292,000 schoolchildren, and a later one in 1986 examined 135,000 children. A map from the 1986 survey showed approximately 20 districts with a goiter prevalence of 0-5%, eight with 5-10%, six with 10-20%, and five with 20-30%. The most affected parts were in the northeast and center. A study of several pilot stations showed some areas with prevalences of 40-50%. A survey in 1991 of schoolchildren, age 6-16, in each district showed median urinary iodine concentrations of 3.7-5.4 mg/dl in 11 districts, and 5-13.1 mg/dl in the others.

Romania uses potassium iodate, 15-25 mg/kg of salt, by legislation. The iodate is imported from the Netherlands. The country has five salt mines, each with iodization equipment. Iodized salt is distributed to only 30 districts. It is packed immediately after iodization and sent to commercial units. Distribution is currently unsatisfactory because of high costs of transportation and socioeconomic difficulties, resulting in prolonged storage. Antiepidemic health units of the Ministry of Health are responsible for monitoring, which they carry out by measuring iodine levels in the salt at the mine and at different steps in its path to the consumer. In some of the districts receiving iodized salt, potassium iodide tablets are also given, one per week to children and two per week to pregnant women.

Spain: Iodine Deficiency - Update of a Widespread and Persisting Problem, by F. Escobar del Rey and G. Morreale de Escobar, Investigaciones Biomédicas and Facultad de Medicina, Madrid, Spain.

IDD in Spain was reviewed in the IDD Newsletter (vol. 3, no. 4, November 1987. The present article updates that information.

A 1982 law mandated the production of iodized table salt, at 60 mg iodine/kg, but decentralization led to a widely variable level of interest in IDD and its correction among the 17 autonomous administrations within the country. Information about the use of iodized salt, especially in rural areas, is insufficient. The coarse salt used for cattle and food preservation is frequently preferred. Some areas have local laws requiring subsidized school lunch programs use iodized salt. Highlights of information about the status in the 17 regions follows.

I. Navarra - The mean goiter prevalence in schoolchildren in 1990 was 13.4%, and the mean urinary iodine concentration was 89 mg/l. In the county of Navascués in the Pyrinees the goiter prevalence was greater than 18%, and the mean urinary iodine excretion was 45 mg/l. In some other villages the excretion was less than 30 mg/l. Cretins were seen, but all were older than 30 years.

II. Aragón - In the province of Teruel, the goiter prevalence was 30% and urinary iodine 81 mg/l, with one area having more than 50% of samples less than 50 mg/l. Hearing tested by audiometry was poorer in goitrous children than in their nongoitrous peers.

III. Cataluña - A vigorous program was set up promoting iodized salt and fish consumption. In one area, Cerdaña, goiter prevalence in 1983 was 35%, and 28% in 1990; the mean urinary iodine excretion increased from 78 mg/l to 175 over the same period, and by 1990, less than 2% of urine samples were less than 50 mg iodine/l.

IV. Valencia - No information.

V. Murcia - A 191 study of 1954 schoolchildren from different areas showed a mean goiter prevalence of 29% and a mean urinary iodine excretion of 94 mg/l. The goiter prevalence ranged from 51% in Altiplano to 24% in Mar Menor. Children with goiter had lower urinary iodine levels and lower school grades. For example the children with the lowest school grades had urinary iodine excretions of 37 mg iodine/l compared with 96 mg/l for those with better scores.

VI. Andalucia - A comparison of three groups, given respectively (A) no intervention, (B) oral iodized oil, or (C) iodized salt at school, showed the following results: A (no intervention), goiter increased from 39% to 52% and urinary iodine decreased from 70 to 47 mg iodine/l; B (oral iodized oil) goiter prevalence decreased from an initial 32% to 16% (1 yr), 23% (2 yr), and 28% (3 hr), while urinary iodine went from 65 mg/L to 113 (1 yr), 90 (2 yr), and 114 (3 yr); and (iodized salt) one year after introduction, goiter decreased from 44 to 28% and urinary iodine rose from 52 to 103 mg iodine/l. These data were from Sevilla, Huelva, and Cadiz; no new information came from the remainder of Andalucia, where previous surveys had shown widespread endemic goiter.

VII. Extremadura - New surveys have been carried out in more than 3000 schoolchildren in areas with severe iodine deficiency, but results were not yet available. However, little iodized salt is sold, so severe iodine deficiency probably still persists.

VIII. Castilla-La Mancha - Schoolchildren surveys in Toledo showed a goiter prevalence of 19%, and urinary iodine levels of 110 mg/l; in Guadalajara 18% goiter, urinary iodine 112 and Cuenca, goiter prevalence 25%, urinary iodine 72. Some villages had goiter prevalences as high as 86%, and urinary iodines as low as 34 mg/l. IX. Madrid - A small 1984 survey showed 18% goiter and mean urinary iodine excretion of 102 mg/l in schoolchildren.

X. Castilla-León - La Cabrera in the province of León, an area of historically severe iodine deficiency, had a 70% goiter prevalence and mean urinary excretion of 13 mg/l in schoolchildren. Overall the goiter prevalence in several areas of northwest León was 34.7% and the mean urinary iodine excretion 52 mg/l.

XI. La Rioja - No recent information.

XII. Pais Vasco - A recent study in schoolchildren chosen at random from the whole region showed an overall goiter prevalence of 21.4% and a mean urinary iodine excretion of 75 mg/l. Iodized salt was introduced in 1982, but these figures suggest it is not widely used.

XIII. Cantabria - No new information.

XIV. Asturias - Studies in 1982 showed a goiter prevalence of 21%, reaching 3% in the western part, and mean urinary iodines of 54 mg/l. In a 1987 follow-up in schoolchildren after compulsory iodized salt use in school kitchens and advocacy for its general use, goiter prevalence was still 22%, although it had decreased in some of the previously severe areas. Thus, the iodized salt program was not achieving the desired effect.

XV. Galicia - A survey in the province of Pontevedra showed no endemic goiter and urinary iodine excretion of 91 mg/g creatinine. In the province of Lugo, after use of iodized salt in school kitchens, goiter prevalence on the coast decreased from 21% to 10%, and urinary iodine rose from 113 to 165 mg/l, however, in the interior goiter remained about the same (37% to 44%) despite an increase in urinary iodine from 26 to 88 mg/l. These findings suggested that iodized salt at one meal may help moderate iodine deficiency but not be adequate for more severe degrees. Further follow-up is underway, and results from 1990 suggest that most of the province of Lugo still has iodine deficiency.

Also, the province of La Coruña on repeat survey in 1990 showed little improvement from iodized salt given in school lunches; goiter prevalence in schoolchildren went from 78.8% in 1982 to 64% in 1990, and urinary iodine rose from 16 to 48 mg/l.

XVI. Las Canarias - 1985 surveys of schoolchildren in the province of Santa Cruz de Tenerife the goiter prevalence was 11%, reaching 21% in some communities. A 1989 survey on the island of Fuerteventura showed a goiter prevalence of 23% and a mean urinary iodine excretion of 89 mg/g creatinine, with the most severe community having 54% goiter and urinary iodine of 64 mg/g creatinine.

The authors of this careful report conclude that iodine deficiency persists through large areas of Spain. Iodized salt is available but is not widely used. Production of iodized salt currently represents about 12% of table salt. The compulsory use of iodized salt for school lunches in several areas has had only a modest effect. There is no still national program. The Spanish society of Endocrinology has supported a declaration for IDD eradication and presented it at a meeting for distribution to health authorities at the local and national level.

Sweden: The State of Iodine Nutrition, by F. A. Karlsson, University Hospital, Uppsala, Sweden.

A 1931 map described goiter in the middle and southeast parts of the country, and estimated as many as 300,000 persons with goiter and 1,000 cretins in Sweden at a time when the population was six million. Reports of the iodine content of water have ranged from less than 0.5 mg/dl to more than 1. The goiter prevalence apparently increased during the 19th century, perhaps due to food shortages and to a shift in diet from sea fish to potatoes. Milk is an important source of iodine, containing about 10 mg iodine per 100 ml, attributed to an increase in iodine supplementation of basic cow feeds.

In 1933 the Swedish Health Authority recommended 10 mg KI per kg table salt, increased to 50 mg/kg in 1966. Current estimates of total intake are 200 mg/day, the larger part derived from milk and dairy products. A 1970 survey of a previously goitrous area showed no thyroid enlargement in schoolchildren. Scattered data on urinary iodines available over the last 20 years give average values of around 90-150 mg/l.

In conclusion, endemic goiter no longer appears to be present in Sweden, but no recent surveys are available to confirm this impression.

Switzerland: Status of Iodine Nutrition, by H. Bürgi, Z. Supersaxo, and P. Dürig, Medizinische Klinik, Solothurn, Switzerland and University of Berne, Berne, Switzerland.

A recent IDD Newsletter (vol. 7, no. 3, August 1991) described the history of salt iodization in Switzerland. A 1988 survey of 1207 schoolchildren, age 7-16, in the canton of Berne showed 9.8% graded goiter 1a, 1.0% 1b, and 0.3% grade 2, giving a total goiter rate of 11.1%. Urinary iodine excretion in the same study was 160 mg/g creatinine. Newborns in Zurich had excretions of 7.0 mg/dl. Currently the salt is iodized at 15 ppm, the mean urinary iodine excretion is 150 mg/day, and the mean 24 hour radioiodine uptake is 22%.

Salt is iodized both for household and food industry use. In 1989, 78% of all salt for human consumption was iodized, including 92% of household salt. Some of the non-iodized salt in the food industry is for export to countries that restrict iodine levels. Iodized salt costs the same as the non-iodized. Almost all of the cantons have transferred their salt monopoly to the United Swiss Rhine Salt Works, of which they are the exclusive share holders. Supervision of the IDD program rests in the Fluorine-Iodine Commission of the Swiss Academy of Medical Sciences, whose members include public health officials, dentists, thyroidologists, food chemists, pharmacologists, and salt manufacturers. This Commission reports to a larger Federal Commission of Nutrition, which in turn recommends legislative and executive action to the Conference of the 26 Cantonal Health Ministers.

The authors note that while the Swiss program has been quite successful, it is threatened by impending international trade regulations that block monopolies and prevent "artificial" low pricing of iodized salt.

Turkey: Endemic Goiter and Iodine Deficiency, by H. Hatemi and I. Urgancioglu, Internal Medicine Department, Istanbul University, Istanbul, Turkey.

A 1956 summary described goiter principally in three regions, Isparta-Burdur in western Anatolia, Kastamonu in the western Black Sea region, and Rize-Giresun in the eastern Black Sea region. A 1984 summary showed that except for seafood, most other food sources in Turkey had considerably less iodine than those from iodine-sufficient countries like the United States. A 1980 survey found the iodine concentration in drinking water was below 10 mg/l in 49 of 493 areas studied. In a survey of 1987 of 73,750 people in 115 residential districts, the goiter rate was 30.5% on a national basis. Studies in children showed that 26% of the communities sampled had over 10% of children with grade 2 goiter; figures were not given for total goiter rate.

United Kingdom: Status of Iodine Nutrition, by J. H. Lazarus, D. I. W. Phillips, A. B. Parkes, P. P. A. Smyth, and R. Hall, Department of Medicine, University of Wales College of Medicine, Cardiff, Wales; and University College Dublin, Dublin, Ireland.

A 1976 study estimated daily iodine intake at 86 mg/person, while a 1977-79 survey, also based on food sample analyses, indicated an average intake of 723 mg/person/day. Major sources include fish, dairy products, and cereals. A 1990 survey of schoolchildren in south Wales, age 9-11, showed a mean thyroid volume of 5.49 ml, and mean urinary iodine levels of 105 mg/g creatinine. Milk from dairies in seven British towns showed an average iodine content ranging from 130-200 mg/l, with a median in February (235 mg/l) almost twice that in May (119 mg/l) and this correlated with lower urinary iodine levels in May. In a study in 1988-90, iodine excretion in nonpregnant women was 73 mg/g in the summer and 98 mg/g in the winter.

Britain has no iodine supplementation program, and only 2.5% of salt for consumption is iodized. The authors estimate that the current average dietary iodine intake is approximately 255 mg/day, almost none of it from iodized salt. They note the need for continued monitoring, and suggest more attention to regulating the iodine content in milk.

Iodine Nutrition in Other Countries

Australia: Status of Iodine Nutrition, by C. J. Eastman, Westmead Hospital, N.S.W., Australia.

Manifestations of iodine deficiency are historically limited to the mountains of the Great Dividing Range in the eastern part of the country and the island of Tasmania. When first surveyed in 1949, the goiter prevalence in Tasmania was 51% in school girls, and 36% in boys. In the Australia Capital Territory, centered around Canberra, goiter was recognized, but no surveys or other data were recorded.

Prophylactic programs included potassium iodide tablets of 10 mg given to mothers and small children in the Capital Territory, and from 1949-1966 given to all schoolchildren in Tasmania. Beginning in 1963 in Canberra and in 1966 in Tasmania, potassium iodate was substituted for potassium bromate in baking, estimating that this would give an iodine intake of approximately 100 mg/day. The prevalence of goiter decreased steadily in both areas, and had disappeared by the 1970's. This decrease had begun long before bread iodization, and is probably attributable to food diversification and other exogenous sources of iodine.

An increase in hyperthyroidism occurred in older patients shortly after the introduction of iodate in bread. Initially this was thought to be causative, but careful investigation traced this Jod-Basedow to iodine-containing disinfectants used by farmers for cleaning cows' udders.

Currently, urinary iodine excretion is monitored regularly in several Tasmanian schools, with levels ranging from 229 mg/l to 356. Mean levels for Sydney are 180 mg/l. Neonatal screening with a sensitive assay shows that in the iodine-sufficient state of New South Wales, 99% of neonatal TSH levels are below 6.7 mU/ml, and 99.9% below 14. Similar values were found for Tasmania. Currently, there is no evidence for IDD in Australia. However, there is no national surveillance program.

Japan: Status of Iodine Nutrition, by S. Nagataki, Nagasaki University School of Medicine, Nagasaki, Japan.

Over the years it has been recognized that the Japanese diet is high in iodine, and various studies have shown mean urinary iodine excretions of 739-3,286 mg/day on regular diet, but with very wide ranges, from 90 mg/day to 19 mg. Variation from day to day was also noted. A recent study in six medical schools showed values ranging from 910-1760 mg/day in patients not receiving iodine-containing medicine. Another study of hospitalized patients showed urinary iodine excretions of around 200 mg/day in those not ingesting seaweed.

The major dietary source of iodine in Japan is seaweed. "Tangle," or Laminaria japonica, is 3% iodine by dry weight, and one bowel of Tangle soup can contain 5 mg of iodine. Tangle is also used for a candy-like chewing gum. Another custom is to immerse a Tangle root in water overnight and drink the water the next morning, which can contain 20-30 mg of iodine. Undaria (the Japanese name is Wakame), another seaweed that is also a popular food, is about 0.025% iodine by dry weight. Several other seaweeds also have high levels of iodine, but many others do not.

This paper also compared thyroid diseases in Japan with those in England and suggested that goiter was lower but hypothyroidism was higher in Japan. Dr. Nagataki also noted that he had never seen Jod-Basedow in Japan. In the discussion, Dr. Hetzel emphasized that Jod-Basedow should be viewed as a complication of iodine deficiency itself rather than as a result of stable iodine sufficiency.

Short Presentations

The workshop also invited free communications related to IDD. Abstracts of some of these follow.

Iodine Deficiency is Still Existent in East Germany (W. Meng, G. Kirsch, A. Schindler, G. Furcht, R. Hampel, U. Ermisch, U. Tuschy, M. Ventz, H. Kerber, H. J. Heberling, H. Rühle, Klinik für Innere Medizin, Universität Greifswald, Germany)

Reunification of Germany has repealed the mandatory salt iodization previously in effect in the former East Germany. Iodized salt consumption has decreased from 84% to 20% and iodized mineral mixtures are now used less in animal feeding. In Greifswald, the urinary iodine excretion in 1991 was 33 mg/g creatinine, compared with 62 in 1987. Urinary iodine excretion data from 1990 ranged from 33 to 53 mg/g creatinine, being particularly low in Berlin, Leipzig, and Schwerin. Public education about the importance of iodine prophylaxis is needed.

Iodine Excretion, Compliance of Patients and Changes in Thyroid Volume During Therapy of Endemic Goiter (J. Rendl, S. Seybold, K. Schlisske, W. Böner, Clinic and Policlinic for Nuclear Medicine, University of Würzburg, Würzburg, Germany)

The authors gave patients one of three treatments for endemic goiter: (a) an average of 200 mg iodine per day; (b) 150 mg thyroxine per day; or (c) 100 mg of iodine plus 100 mg of thyroxine per day. In all groups urinary iodine excretion increased, and thyroid volume decreased. There were no significant differences among the three types of treatment and it was concluded that the important feature was receiving sufficient amounts of iodine.

Iodine Intake, Iodine Excretion and Goiter Prevalence in Southern Poland(D. Tylek, M. Rybakowa, K. Dluzniewska, J. Pulka, R. Drozdz, B. Holynska, B. Ostachowicz, Endocrinological Department, Institute of Pediatrics, Medical Academy, Krakow, Poland)

One thousand nine hundred forty-five children age 3-16 were surveyed for goiter clinically and by ultrasound. Goiter prevalences ranged from 25 to 54%, and urinary iodines were in the range of 45 mg/l, indicating significant iodine deficiency in this area.

Goiter Caused by Iodine Deficiency Among Schoolchildren in Kielce Province/II/ (M. Szalecki, Children's Hospital, Kielce, Poland)

In a survey of 253 nongoitrous children age 6-15, urinary iodine excretion was 48 mg/g creatinine.

The Utility of Thyroid Ultrasound During Epidemiological Studies of Endemic Goiter (P. Vitti, F. Aghini-Lombardi, L. Antonangeli, M. Giachetti, D. Maccherini, M. Bellipanni, T. De Paolis, P. Nanni, L. Giusti, A. Pinchera, Istituto di Endocrinologia, University of Pisa, Pisa, Italy)

In 719 children, age 6-14, in northwestern Tuscany, the mean urinary excretion was 119 mg/l (90.4 mg/g creatinine), 9.2% had goiter, and the mean thyroid volume by ultrasound ranged from 2.1 ml in six year olds to 6.7 in 14 year olds. Thyroid volume correlated directly with age, weight, and height, and inversely with urinary iodine. By WHO criteria the goiter prevalence was 9.2%, but using ultrasound criteria (defining a goiter as a thyroid volume greater than two standard deviations from the mean for the age group), the goiter prevalence was 3.1%. The authors concluded that ultrasound is more accurate than palpation and should be used in surveys.

Iodine Deficiency, Goiter Prevalence and Thyroid Autoantibodies in Children from Chernobyl (W. Greil, B. Strobl-Greil, H. Reissenweber, C. R. Pickardt, University of Munich, Germany)

The authors studied 65 children from Lviv, Ukraine, resettled there after Chernobyl. The median urinary iodine was 37.8 mg/g creatinine, 23% had positive thyroglobulin antibodies, serum thyroglobulin levels were 15 ng/ml, thyroid volume by ultrasonography was 54% above the upper limit of normal established for iodine sufficient children of similar age. The data suggested mild to moderate iodine deficiency in this area of Ukraine.

Iodine Content of Formula Milk Preparations for Preterm Babies and Newborns in Spain (S. Ares, J. Quero, G. Morreale de Escobar, Neonatology Department, La Paz and Istituto Investigaciones Biomedicas, Madrid, Spain)

The study compared the iodine content of milk samples from mothers of preterm infants in Madrid with that of samples of formulas for preterms and normals, the latter corresponding to 25 different preparations from eight different manufacturers. Maternal milk had a mean iodine content of 10.9 mg/dl, whereas formulas for preterms and newborns were 6.8 and 5.6 mg/dl, respectively. Only six of the 25 preparations had as much iodine as maternal milk. The iodine intake of preterm infants was clearly below the standard recommended amount. Thus the majority of the formulas do not contain adequate amount of iodine, and most preterms are not obtaining enough iodine.

Neuropsychological Development in Different Iodine-deficient Areas of Tuscany (Italy) (A. Antonelli, L. Gasperini, C. A. Pruneti, S. Neri, G. Baracchini-Muratorio, L. Baschieri, Institute of Clinical Medicine II - University of Pisa; U.S.L.-15, Alta Val di Cecina, Tuscany; Infantile Neuropsychiatric Service, U.S.L.-12, Pisa, Italy)

The authors studied normal schoolchildren from three iodine-deficient areas (Montefeltro, 65% goiter prevalence, UI 40 mg/g creatinine; Lunigiana, 57% goiter prevalence, UI 49 mg/g creatinine; and Alta Val di Cecina, 40% goiter prevalence, mean urinary iodine 58 mg/g creatinine) and a control group from Pisa, mean urinary iodine excretion 88 mg/g creatinine. The Raven's Progressive Matrices 47 Colors Test was used, and the mean scores were: Montefeltro 25.2, Lunigiana 26.5, Alta Val di Cecina 27.9, and Pisa 30.1. The first two were significantly lower than the control group. The authors suggest that schoolchildren from iodine-deficient areas may have some mild mental impairment, proportionate to the degree of iodine deficiency.

Urinary Iodine Concentration, Thiocyanate Excretion and Hearing Capacity in Children (P. Valeix, G. Benoit, P. Preziosi, Cl. Rossignol, S. Hercberg, Paris, France)

The authors found median urinary iodine values of 18.4, 13.4, and 11.6 mg/dl in children age 10 months, two years, and four years, respectively. The fractions of children with urinary iodine values below 10 mg/dl were 17.6% for 10 month olds, 32.2% for two year olds, and 37% for four year olds. Hearing was more likely to be impaired in those with urinary iodines less than 10 mg/dl than in those above.