Volume 8 Number 1, February 1992

IN THIS ISSUE

IDD in the Former USSR

An international symposium on the elimination of IDD, with special reference to the USSR, was held in Tashkent, Uzbekistan from November 18-22, 1991, sponsored by ICCIDD, WHO, and UNICEF, and hosted by the USSR. Dr. Gregory Gerasimov and Dr. Rainer Gutekunst, both of the ICCIDD Board, arranged and collated the presentations, and are editing these for publication.

A number of international speakers discussed various general aspects of IDD, including Dr. B. S. Hetzel, Dr. John Stanbury, Dr. Rainer Gutekunst, Dr. Claude Thilly, Dr. Robert DeLong, Dr. Lester Van Middlesworth, Dr. Hans Burgi, Dr. M. Anke, Mr. David Haxton, and Dr. Ma Tai. Most of these talks were on general IDD topics. In addition, many Soviet colleagues presented data from their own republics and areas, information that was previously not available to the international world.

The present report summarizes many of these presentations, from the documents edited by Drs. Gerasimov and Gutekunst. The conference took place in the waning days of the USSR, so some of the geographical references need updating.

Endemic Goiter in the Former USSR: Problems and Solutions.

I. I. Dedov, National Endocrinology Research Center, Moscow, Russia.

In the former USSR iodine deficiency affects vast territories in the Urals, the Caucasus, Siberia, Central Asia, the middle reaches of the Volga, and other regions. Biogeochemical "provinces" with environmental deficit of iodine and other trace elements that may modulate effects of iodine deficiency cover more than a half of the former USSR's territory. Over 50 years ago Soviet scientists suggested a strategy to eradicate endemic goiter from most of the country by compulsory iodine prophylaxis. A field trial carried out in the Kabardino-Balkarskaya Autonomous Republic and other endemic areas was promising, but the Second World War halted these efforts and goiter prevalence increased over the next 3-5 years in those areas.

During the immediate post-war period, prevention and control of endemic goiter again became a priority for the health care system in the USSR. First, a system of goiter control units was established (afterwards transformed to the endocrinological health service), consisting of a network of specialized dispensaries covering the most affected areas. Next, health personnel (endocrinologists) were trained and the sanitary and hygienic services became involved. Finally, relevant sectors of the national economy were motivated to participate and the national salt industry began producing iodized salt, a major advance in combatting endemic goiter. In 1956, the USSR Ministry of Health issued Order No. 37-M entitled "Towards Improvement of Control and Prevention of Endemic Goiter." It greatly advanced implementation of the control program throughout the country and secured political support and commitment of the government for mandatory iodine prophylaxis in all endemic areas. By the 1970's, the goiter prevalence had decreased many-fold and the most serious complications of iodine deficiency, including endemic cretinism, severe myxedema, large nodular goiter, etc., had almost disappeared. Effective therapy of affected populations resulted in a significantly lowered morbidity in areas where endemias still persisted.

Two measures were crucially important for the positive changes outlined in the previous paragraph: the rapidly growing production of iodized salt to ensure universal iodine prophylaxis in endemic areas, and the expansion of the network of goiter control units (63 dispensaries were set up in endemic regions by 1970, their primary task originally being prevention and control of endemic goiter).

During the pre-war period, Narkomzdrav (the Ministry of Health) set up the Central Commission for Goiter Control to help organize the national service for prevention and control of endemic goiter. The Commission was responsible for planning, monitoring, and coordination of activities within the framework of the national program. The Commission addressed the problem in close collaboration both with government ministries and with the regional committees for endemic goiter control that had been set up in republics, territories, and provinces. The regional committees consisted of local government (Executive Committee), medical, and health officials and representatives of education, marketing, and other sectors. This composition proved very effective in that it allowed political, economic, administrative, and other obstacles to be rapidly overcome.

The state prevention and control statistics for endemic goiter was discontinued in 1970, a move that made it impossible to monitor morbidity dynamics at the national level. In 1990, the National Research Center for Endocrinology, USSR Academy of Medical Sciences, organized a questionnaire survey to document goiter prevalence in the country. It recorded 1,044,767 persons with overt goiter, a marked rise over the 1969 figure. In certain regions, the number of patients increased by 24 to 117% between 1988 and 1990. This trend paralleled a recession in the production of iodized salt to 56.0-65.5% of the overall demand, and an absence of properly controlled prophylaxis.

Currently, the system of goiter care in the USSR is at a critical state, its worst in the past 40 years. In addition to ineffective universal iodine prophylaxis and, in certain cases, group prophylaxis using antistrumin, the following factors contribute to the problem:

Neither government nor other public bodies are paying proper attention to the goiter problem. Prevention and control of iodine deficiency are currently a matter of concern of local authorities who must act without adequate financial or technical support from the central government.

The goiter control program should include a National Committee for Goiter Control and regional committees (in republics and provinces) as functional bodies of local health administration. The committees may be integral parts of a professional association or work in collaboration with it. A long-term goiter control program should be developed with legislative power to coordinate all scientific and practical work including that of the Association for Goiter Control.

Other important features of the program should be:

Epidemiology of Endemic Goiter in Belarus.

E. A. Kholodova and L. P. Fedorova, Department of Endocrinology, Institute for Advanced Medical Training, Minsk, Belarus.

The history of endemic goiter studies in Belarus dates from the 1920's. Results obtained by different authors at that time were contradictory. For example, during examination of schoolchildren in Minsk in 1925-1927, I. P. Dragun found enlarged thyroid glands in only 2.5% of them whereas A. L. Lapidus reported the incidence of thyroid enlargement to be as high as 20%.

Regular studies of endemic goiter began in 1935 by the Belarus Antigoiter Station. After the Second World War, the activities in this field were resumed in six regions of Belarus. Repeated examination of the residents in 692 settlements revealed thyroid enlargement of all stages in 8-10%, including larger goiters in 2.5%. Among patients with thyroid hyperplasia and goiter, 92 and 8% had exophthalmic and nodular goiter, respectively. The male to female ratio was 1:8 or 1:5. No cases of congenital goitrous cretinism were recorded. The examination revealed euthyroidism in 95.5%, hyperthyroidism in 4%, and hypothyroidism in 0.5% of the patients.

The situation remained virtually unaltered until the late 1950's. The largest areas of endemic goiter were associated with the boggy peat soils of Gomel'skaya, Mogilyevskaya, Vitebskaya, and Minskaya oblasts (provinces), and goiter was especially prominent in Narovlyansky, Mozirsky, and Turovsky rayons (districts) of Gomel'skaya oblast'. In 1937, goiter (all stages) was recorded in 10-35% of the examined subjects, with 3-10% having larger goiters, and this finding persisted until 1947. In 1957, thyroid hyperplasia was diagnosed in 14.3% of the residents in Gomel'skaya oblast'. In Mozirsky and Turovsky regions, large goiters were found in 5 and 4.5% of the residents, respectively. The overall prevalence in Gomel'skaya oblast' ranged from 5-6%. Examination of 14,000 schoolchildren revealed hyperplasia in 21.6% (8% had large goiters). Outside Gomel'skaya oblast', areas of endemic goiter were reported in Shklovsky and Chaussky rayons of Mogilyevskaya oblast', Berezininsky, Smolevichisky, Lyubansky, and Slutsky rayons of Minskaya oblast', and from Liozndnsky and Skidel'sky rayons of Vitebskaya oblast'.

In the early 1960's, endemic goiter in Belarus was estimated as mild to moderate, based on case records and the incidence of nodular goiter and endemic cretinism. Between 1966 and 1985 the incidence of goiter decreased by 37% but started to rise after 1986. The same trend was observed in individual regions. There was a considerable decrease in the incidence of goiter in 1980 as compared with that in 1970 and a substantial overall rise in 1990 in all regions of Belarus. This rise was highest in Brestskaya and Grodnenskaya oblasts (over 300%) and lower in Gomel'skaya and Mogilyevskaya oblasts, which decreased between 1970 and 1990. The cause of the increased incidence may probably be attributed to at least three factors: (1) more accurate diagnosis, (2) inadequate universal and group prophylaxis after free antistrumin distribution was stopped, and (3) increase in the incidence of endemic goiter due to ingestion of natural goitrogens.

The magnitude of the endemia was also estimated from results of expeditions by specialists of the Belarus Endocrinological Dispensary in 39 districts in several provinces of Belarus. More than one-half of the districts included in the study were reported to be endemic with an irregular distribution.

Factors facilitating development of goiter

It is now universally accepted that iodine deficiency is the major cause of endemic goiter. With this in view, we examined the relationship between the iodine contents in soil and water and the incidence of endemic goiter in different regions of Belarus.

In Belarus Poozerie (Lakeland), S. G. Komrakova and K. I. Lukashev found that the iodine content in turfy podzolic soils is low, as is the iodine concentration in water used for municipal and agricultural supply for this region. Also, this water contains large amounts of manganese and nitrate, both considered to be additional etiological factor for endemic of goiter.

To analyze the relationship of endemic goiter with environmental iodine and other trace elements (manganese, molybdenum, iron, copper, nickel, vanadium), the territory of Vitebskaya, Minskaya, and Grodnenskaya oblasts (provinces) was divided into eight areas of differing prevalences of endemic goiter. The highest prevalence among these areas was five times greater than the lowest, and the mean water iodine levels varied from 1.00-8.00 mg/l. A significant inverse relationship existed between the goiter prevalence and iodine levels in water (coefficient of correlation of 0.52), but not with levels of iron, copper, molybdenum, nickel, or vanadium. P. L. Patent has studied iodine and manganese content in Belarus food stuffs and found a close correlation of the goiter incidence with manganese intake, but not with iodine intake although the daily iodine intake of Belarus residents was found to be only 55 to 71 mg. Other areas of Belarus showed a similar relationship between endemic goiter and iodine content of surface and ground waters.

In summary, the present study suggests that low levels of iodine in water and food, and high contents of manganese and nitrate in water and food, contribute to the high incidence of endemic goiter in Belarus Poozerie. However, geochemical features alone cannot account for the high incidence of endemic goiter in Belarus. Some people in regions with the lowest iodine levels in the environment do not have goiter. Also, the goiter prevalence does not differ dramatically from places with very low environmental iodine to those with nearly normal levels. Finally, long-term control measures for endemic goiter have failed to eradicate the disease completely despite significantly reducing its incidence. Thus, all the factors contributing to endemic goiter in Belarus have not been identified and further investigation is needed.

Prophylaxis of Endemic Goiter in Chelyabinskaya Oblast'.

J. D. Levit, G. M. Korotkova, and A. V. Podolsky, Cheliabinsk Endocrinology Dispensary, Cheliabinsk, Russia.

Chelyabinskaya oblast' (province) is a part of the Ural endemic area. Publications from the second half of the last century (Ber, 1857; Petukhov, 1858; Kondaratsky, 1889) described endemic goiter and its severity in the Urals and adjoining areas. For example, from 71 to 91% of the population were affected in the areas of Zlatoust, Kurgan, and Perm (Schwartzman, 1932) and cretinism was noted. A survey in 1929-1931 examined 18.6% of the total population (134,054 persons) living in 25 districts found an overall goiter prevalence of 30.7%, and an 8% prevalence of large goiters, particularly in the mountainous and western parts of the territory.

Geochemical surveys (Miloslavsky, 1983; Besprozvannikh and Guber, 1933; Remezov et al., 1935) have shown that the Urals are iodine deficient, and further studies confirmed iodine deficiency in soil, water, and foodstuffs in different zones of this province. According to K. Z. Kireeva (1971) the iodine content in locally produced foodstuffs in Chelyabinskaya oblast' varied from 2.5 mg % in the mountainous forest zone to 3.5 mg % in the steppe zone.

Table 1 compares several surveys during the past 50 years, showing a marked decrease especially in large goiters [Ed note: criteria for goiter, particularly in the early studies, are not available.]

The decline in total goiter prevalence was much less conspicuous. Its prevalence in children remained high (22.3 cases per 100 subjects). In Zlatoust the prevalence was 15.5% in 30,751 children examined in 1971-1975 and 12.8% in 18.988 examined in 1986-1990.

The number of children with large thyroids fell from 3.0 to 1.4 per 1,000 subjects. Over the half century, cretinism and hypothyroidism disappeared and Kovalev in 1966 found no cases of nodular goiter at autopsy in 1,000 children.

Urinary iodine excretion in healthy subjects living in Chelyabinskaya oblast' has been near normal in the steppe zone but lower in the mountainous forest and forest-steppe zones (Table 2). Urinary iodine excretion was positively correlated with the iodine content in food products (R = 0.89) and negatively with goiter (R = (-) 0.77).

The above data characterize rural populations. Inhabitants of the cities of Zlatoust and Chelyabinsk had urinary iodine levels similar to each other. However, the mean value for Zlatoust was 127.4 ± 10 mg/24 hours, compared with 80 ± 3.7 mg in the rural population of the mountainous forest zone (p < 0.01). Costa (1973) has previously noted that endemic goiter is largely a problem of rural areas because townspeople consume large amounts of imported food included sea products. The annual sale of sea fish in Chelyabinskaya oblast' increased by a factor of 2.7 between 1961 and 1978. It is also possible that a part of the iodine ingestion by townspeople is from industrial waste. Mean urinary iodine excretion was 45.7 mg/24 hours for 30 children age 5-10 in Chelyabinsk city and 82.3 mg/24 hours in 140 children age 11-15. This difference was probably attributable to age-specific differences in body weight although the effect of other factors such as enhanced functional activity of the thyroid gland around puberty cannot be excluded.

The present study suggests that iodine deficiency has been effectively corrected in Chelyabinskaya oblast'. People in big cities of the steppe zone already receive adequate amounts of iodine whereas intake in rural populations approaches the lower limit of normal. Iodine prophylaxis appears to be well organized in that only iodized salt has been on sale since the 1950's and day nurseries, kindergartens, schools, and woman's consultation centers are well supplied with antistrumin for free distribution. Additional intake of iodine as antistrumin is easy to monitor, whereas its ingestion with foodstuffs, drugs, and industrial waste needs more sophisticated technologies to be controlled.

Excessive iodine intake may have the unfavorable consequences of increasing the frequency of thyroid autoimmune diseases, especially autoimmune thyroiditis. Some authors postulate a direct casual relationship between iodine prophylaxis and increase in thyroid autoimmune disease (Weaver et al., 1966; Boukis et al., 1983; Harech et al., 1985; Oechlin et al., 1985). To assess this we determined the incidence of autoimmune thyroiditis in surgical thyroid specimens from different natural zones of Chelyabinskaya oblast', using materials generously provided by Professor V. A. Krizhanovsky (Clinic of General Surgery, Chelyabinsk Medical Institute), and compared them with goiter incidence for the same region. About 95-98% of all thyroidectomies in Chelyabinskaya oblast' are performed in this clinic. We found that the mountainous forest zone had an 8.8% incidence of autoimmune thyroiditis in surgical thyroids, a food iodine content of 2.5 mg %, and a goiter incidence of 2.3 per 1,000. Respective figures for the forest-steppe zone were 12.6%, 3.0 mg %, and 1.4/1,000, and for the steppe zone, 13.5%, 3.5 mg %, and 0.9/1,000. The correlation between dietary iodine content and incidence of endemic goiter was -0.93, and between dietary iodine content and percentage of patients with autoimmune thyroiditis, +0.88. For comparison, histologic autoimmune thyroiditis was diagnosed in 27 of the 2,247 thyroids (1.8%) for Chelyabinskaya oblast' in 1961-1967 (Obraztsov, 1969), and in 383 of 2,738 (14%) in 1977-1980, a 12-fold increase. The incidence of endemic goiter decreased from 1.7 per 1,000 persons to 0.6 per 1,000 persons during the same period. Currently, autoimmune thyroiditis is the most prevalent thyroid disorder in Chelyabinskaya oblast'. Thus as the incidence of endemic goiter drops, the major task is to prevent excessive iodine intake.

How then should iodine prophylaxis be approached if its discontinuation threatens a new outbreak of endemic goiter but its expansion may facilitate development of autoimmune thyroid diseases? "The golden mean" appears to be the attainment of the minimal necessary pool of iodine in the body to prevent and control endemic goiter. Urinary iodine excretion, which reflects iodine saturation regardless of how it enters the body, may serve as a marker. The optimal iodine excretion in urine appears to be about 100 mg/24 hours.

We suggest that iodine prophylaxis should be adapted to the specific conditions of each geographic region. Even within the territory of Chelyabinskaya oblast' there are at least three zones with differing iodine contents. The standardized fortification of all edible salt with 25 mg I/kg over all the vast territory of the USSR disregards specific conditions of iodine ingestion that may differ significantly even within a small area. Therefore, it should be monitored permanently by urinary iodine excretion, using the results to adjust iodine prophylaxis.

We found that 10-15% of subjects with intact thyroid glands had urinary iodine levels of over 300 mg/24 hours. This was mostly due to kelp (Laminaria) and other sea products being extensively advertised and to iodine-containing drugs that are being used in increasing amounts. A great misfortune for the inhabitants of endemic areas, especially those susceptible to extra iodine in their diets, has been propaganda for the so-called "macrobiotics," urging daily consumption of seaweeds and substitution of table salt by sea salt (Milnikov and Sirota, 1990).

Unicap, a USA-produced multivitamin and mineral tablet is currently marketed widely in this country. It contains 150 mg of iodine per dose. Also, inhabitants of iodine-deficient areas use iodine tincture extensively and in an uncontrolled manner, to combat or prevent goiter. Physicians do not always take into account that such medicines as cordarone, solutan, Traskov mixture, enteroseptol, mexase, mexaform, agents used in contrast radiography, etc., contain iodine to which inhabitants of iodine-deficient areas show increased sensitivity. Such populations may be at risk for developing hyperthyroidism and autoimmune thyroiditis. Because excessive iodine intake in iodine-deficient areas can be quite common, it is very important that health personnel and students be made aware of these potential problems.

The present communication demonstrates the necessity of strict control over iodine prophylaxis. Prevention of iodine deficiency must be balanced by a system of equally effective measures to preclude excessive iodine intake and its consequences.

References

Table 1. Goiter surveys in Chelyabinskaya oblast' from 1929 to 1978.

Table 2. Urinary iodine excretion in healthy subjects, iodine content in food products, and prevalence of endemic goiter (calculated from the number of visits to health and medical centers) in different natural zones of Chelyabinskaya oblast'.

Figures in parentheses are numbers of samples determined.

Iodine Deficiency and its Clinical Manifestations in Kazakhstan

M. E. Zeltser, B. A. Aidarkhanov, I. M. Berezhnaya, G. G. Speransky, R. B. Bazarbekova, A. A. Nurbekova, S. A. Levina, N. V. Mandrovnaya, A. A. Aripova, Institute of Prophylactic Pathology, Alma-Ata, Kazakhstan.

Iodine deficiency in Kazakhstan has been assessed by long-term multidisciplinary studies, including iodine levels in water (1,945 samples), soil (881), certain food products, and individual diets (1,704), and by clinical examinations in 441 widely distributed settlements (271,831 persons). The data have made it possible to divide the republic's territory into several zones of differing iodine deficiency.

The zone of severe iodine deficiency includes areas having soils with the lowest iodine content, usually less than 1,000 mg/kg air-dry matter and less than 4 mg/l in water. The iodine content in 78% of daily diets was below 100 mg and less than 50 mg in 42% of them. The prevalence of endemic goiter in most settlements is 35-40%. This zone includes the Karatau mountains and their foothill area, the western spurs of the Talas and Kirghiz ranges, Zailiysky and Dzhungarsky Alatau with the adjoining western and southeastern parts of the Balkhash - Alakul hollow. Making a sharp climb to the north at the eastern banks of Lake Balkhash, the zone of severe iodine deficiency reaches the eastern edge of the Kazakh low-hill area on the border of Kazakhstan. Tenghiz hollow, and basins of the Seleta, Ishim, Bukhtarma, and Uba (both upper and middle reaches) rivers are also severely iodine deficient.

The moderate iodine deficiency zone includes areas with prevailing levels of 4-10 mg I/l in water from different sources and 2,000-3,000 mg/kg in soils. It also includes territories with an iodine water level of 10-20 mg/l but with marked iodine deficiency in soils (less than 1,000 mg/kg). The average iodine content in human diets is almost normal (95.2 ± 5.9 mg/day) and the percentage with very low iodine intakes is not large (12.6%). Most of the diet samples (51.1%) are slightly deficient in iodine (50-99 mg/day). The overall goiter prevalence in most settlements varies from 11-30%. This zone covers the northern part of the Caspian lowlands, spreads along the right bank of the Ural river to Obshi Syrt, stretching from the Aral Sea area to the southern spurs of the Ukutau mountains and along the left bank of the river Sir-Darya. It also occupies the territory between the rivers Chu and Talas, the southeastern portion of the Betpak-Dala plateau, the narrow strip along the northern bank of Lake Balkhash and makes a sharp turn to the north through the Kazakh low-hill area including the Kulunda plains and the eastern part of the North Kazakhstan plains. The Trans-Ural and the Turghai plateaus, the Turghai and the Ishim plains, the Kokchetav hills with the surroundings of the Kapchagai storage lake, Zaisan hollow, and the lower reaches of the rivers Bukhtarma and Uba on the east also belong to this zone.

The relative iodine deficiency zone is of special interest. Iodine levels in its water bodies exceeds 20 mg/l, with the soils being moderately deficient in this microelement (3,000-4,000 mg/kg). Iodine in the human diet is normal (more than 100 mg/day). Nevertheless, more than 10% of the total population in all settlements of this zone have goiter, suggesting the presence of goitrogens other than iodine deficiency. This zone comprises four separate areas: (1) a valley along the middle reaches of the Ilek river; (2) the southern spurs of the Ukutau mountains and the Kengir storage lake vicinity; (3) the central part of the Kazakh low-hill area; and (4) the outlying area of the Kokchetav hills and the central portion of the North Kazakhstan plains.

The iodine sufficient zone consists of the remaining part of Kazakhstan.

Thus, approximately one-half of the huge territory of Kazakhstan appears to be iodine deficient. However, this problem has only recently received proper attention, probably because there had been some decrease in both overall prevalence and severity of goiter. The tendency has been to ignore early forms of endemic goiter even though it is widespread in Kazakhstan and is known to have adverse effects on health. For example, we have shown that children with endemic goiter have significantly enhanced susceptibility to infections as characterized by a low infectivity index. This finding agrees with the results of laboratory tests for resistance to contagious diseases, viz. low lysozyme titers, impairment of phagocyte activity and immune response to vaccination against diphtheria and tetanus. Moreover, unambiguous evidence of immunosuppression has been provided in an experimental study of induced chronic iodine deficiency using animal models.

Selective examination performed in different regions of Kazakhstan over the last three years has demonstrated a high prevalence of endemic goiter. For example, the 1989 screening study in the mountainous village of Kegen (in the zone of severe iodine deficiency), found goiter in 61% of the residents. Many fewer cases were recorded in urban areas of this zone, although endemic goiter was still present. During the 1990 survey in the city of Taldy-Kurgan, 17,798 persons were examined and 22.7% had goiter. Examination of 3,761 children in Alma-Ata found goiter in 9%.

During the last ten years, the overall prevalence rate in the population of Semipalatinskaya oblast' (province) has increased slightly, to 36.9% in 1990, but the frequency of "true" goiter is about 1% according to local endocrinologists.

To study the effect of endemic goiter on the functional state of the thyroid gland in childhood, we suggested that endocrinologists of the Chimkent endocrinological dispensary examine mentally retarded patients in specialized boarding schools. Ten of the 552 children (1.8%) had newly diagnosed severe hypothyroidism whereas 15-18% showed clinical signs of mild hypothyroidism in conjunction with marked mental derangement.

In 1991, we evaluated the state of the hypothalamic-pituitary-thyroid axis in 83 neonates in the Unit of Premature Birth Pathology, Kazakh Research Institute of Pediatrics, Alma-Ata. The babies were transferred to the Unit from city maternity hospitals within three to six days after birth and stayed there for about 30 days, making it possible to investigate dynamics of thyroid hormones and thyroid stimulating hormone levels by measuring each, both at admission and shortly before discharge. Perinatal encephalopathy was detected in 76 of the 83 examined newborn infants, pneumonia in 37, early anemia in 9, and jaundice in 12. Slight asphyxia was recorded in 16 neonates, moderate in 25, and severe in 17. The effect of chronic iodine deficiency appeared especially pronounced in patients with severe somatic pathology. Plasma TSH levels by radioimmunoassays were high in 54% of the 45 neonates, indicating hypothyroidism. Of these, 20% had normal T3 and T4, 60% showed low T4 and normal or elevated T3 levels, and 20% had low T3 and low T4. Repeated examination after 20-25 days showed normalization of the hypothalamic-pituitary-thyroid axis in only 10% of the infants. Therefore, the neonatal hypothyroidism in these children was not transient.

This incidence of neonatal hypothyroidism is much higher than that found in Moscow (2.4% according to I. P. Laricheva, et al., 1991). However, our findings cannot be attributed to iodine deficiency alone since premature birth is associated with a sharp rise in the rate of neonatal hypothyroidism (Yu. A. Knyazev, et al., 1990).

Taken together, these data confirm the clinical significance of Kazakhstan's widespread iodine deficiency and the importance of its correction. The solution of this problem is actually a matter of organization because as far back as the late 1970's we developed a special type of package for iodized salt that allows storage for at least two years without losing iodine.

Iodine Deficiency in Primorie

S. Surkov, N. Nosova, A. Morozova, and L. Osykhovskaya, Vladivostok Medical Institute, Vladivostok, Russia.

Primorie, located in the extreme eastern part of Russia, has been shown to have iodine deficiency (Shevchenko, 1940; Gurevich, 1962; Startseva, 1975; Pastukhov, 1982), manifested by an irregular distribution of endemic goiter in the southern coastal area and in the basin of the river Ussuri. Goiter prevalence in these places was found to exceed 30% (Shevchenko, 1940) as compared with 10-20% in other areas. Iodized salt and antistrumin (potassium iodide formulations) have been the major tools to prevent and control endemic goiter.

Primorie has a monsoon climate with short cold winters and warm summers during which typhoons frequently occur. Fluorine and iodine levels in soil and water are low. In the beginning of 1991, the estimated total population of Primorie amounted to 2,300,000 people. The highest population density was in the southern coastal area and along the railway line connecting Vladivostok and Khabarovsk.

Endemic goiter with varying degree of thyroid enlargement was diagnosed in 2,745 persons (1.2% of the total population) including 411 children under the age of 14. The incidence of different forms of endemic goiter in adults and children is illustrated by the following table. [Ed note: this system grades goiter from mild (I) to very severe (V).]

These data reflect the situation over all Primorie. However, the Dal'negorsky rayon is higher than in other areas. This district is remote from the seaside, isolated by mountains, and difficult to reach even though it has mines, chemical plants, and smelters. Its geographic conditions and environmental pollution may contribute to its high goiter prevalence. The incidence of endemic goiter in the cites of Ussuriysk, Artyom, and Vladivostok is less than 7-10 cases per 1,000 persons and is even lower in other places.

During the last five years, endocrinologists of the Vladivostok Medical Institute have studied the incidence of endemic goiter in medical students and schoolchildren (more than 3,000 subjects). Endemic goiter was diagnosed in 28%, with II degree goiter being prevalent (Kolomiytseva index 4.01%). Hyperplasia was more frequent in females (Lenz-Bauer index 1/6,604). Dynamic studies revealed a slight increase in goiter prevalence (1-2%) supposedly due to newly diagnosed goiter in individuals arriving from nonendemic areas. These findings indicate that according to the criteria of iodine deficiency Primorie should be ranked as a region with mild iodine deficiency.

Daily demand for iodine in man is known to vary from 50 to 200 mg. One cubic meter of maritime air in Primorie contains 20-50 mg of iodine. The diet of the residents is especially rich in sea products including various kinds of fish and sea kale containing about 1% of non-organic iodine. Therefore, iodine consumption in the coastal areas of Primorie appears to be normal, which makes it difficult to account for the high goiter prevalence in this region.

To conclude, further studies are needed to determine daily iodine excretion in urine and evaluate local ecological factors that may influence iodine utilization and metabolism.

Ecological and Genetic Elements in Epidemiology of Endemic Goiter in Tatarstan

V. V. Talantov, V. V. Morozov, F. A. Tazetdinov, and N. F. Alimova, Department of Endocrinology, Kazan Medical Institute, Kazan, Russia.

The first cases of severe endemic goiter in the former Kazanskaya guberniya (province), now partly the territory of Tatarstan, were reported by scientists of the Kazan University more than 100 years ago. Many patients with this disorder were found to develop somatic and neurological complications. Further surveys showed that the soil iodine content of this territory was generally higher than in other regions of Russia (2,500 mg/kg). It was lower only in the areas stretching along the left bank of the Volga. Concern on the part of the local health and medical authorities eventually resulted in the establishment of health service units, three dispensaries, and the Committee for Control of Endemic Goiter, which is responsible for the administration and coordination of the goiter control program. In the 1950's, 18 expeditions to different regions of Tatarstan revealed diffuse thyroid enlargement including I and II degree goiter in 62.5% of the total population, with the incidence of severe goiter and its nodular form amounting to 6.8 and 3.2%, respectively.

On the basis of geochemical analysis, the territory of Tatarstan can be divided into four zones that differ in terms of iodine content in soil, water, and daily human intake. The highest prevalence of endemic goiter was shown to occur in eastern parts of the territory even though their soils were found to be especially rich in iodine (Table 1). A goitrogenic effect of thiocyanate ingestion has been postulated, based on the high sulfur content of these soils.

Major preventive measures to combat endemic goiter have included universal iodide prophylaxis, water supply control, sanitary surveillance over housing conditions, food production, etc. in conjunction with observance of hygienic standards and rules regulating them.

The prevalence of endemic goiter in different areas of Tatarstan has declined continuously during the past decade, from 24.8% to 9.3% for men and from 39.7% to 17.8% for women, with parallel decreases in large and nodular goiters. Table 2 provides details.

Long-term prevention and control of endemic goiter were paralleled by substantial changes in the mode of life and living conditions of the population especially in new rapidly growing urban areas (e.g., Naberezhnie Chelni, Nizhnekamsk) (Table 3). It is worthwhile to note a low rate of decrease in the incidence of endemic thyroid hyperplasia in the urban population, especially among schoolchildren and adults. This trend is obvious in spite of markedly altered dietary habits in the new towns, particularly the import of food including sea products from other parts of the country. Urbanization in some way stresses the thyroid gland and leads to hyperplasia in predisposed individuals.

V. F. Chuprun of the Kazan Medical Institute has demonstrated that in Zapadnoye Predkamye (an iodine deficient area to the west of the river Kama), Tatarstan, relatives of a patient with endemic goiter are at a two times higher risk of developing goiter than individuals in the general population. The chance of developing this disorder in members of families with two or more affected subjects is four times greater than in the general population. There is statistically significant difference between endemic goiter incidence and the degree of kinship with probands. The actual frequency of goiter in the combinations of affected parent/affected child or affected parent/affected sibs complies with that calculated on the assumption of dominant inheritance with partial penetrance (0.7-0.8). The partial penetrance confirms the importance of environmental factors that facilitate expression of genetic predisposition.

Other factors facilitating development of thyroid hyperplasia include goitrogens, malnutrition and overeating, weather conditions, endogenous critical states (pubertal and climacteric periods, illness, etc.), and various medications. Investigation of these effects may be useful in the study of genetic predisposition for endemic goiter, iodine deficiency or both. Consideration of endemic goiter as a predominantly regional public health problem can lead to underestimating factors capable of provoking the disease, in addition to iodine deficiency.

Table 1. Iodine levels in soil, water, and foodstuffs in different natural zones of Tatarstan in relation to the prevalence of endemic goiter (from GM Gil'manova, 1963; RS Tagirova, 1968; AM Khakimova, 1969; AN Yunusova and IB Sitdikova, 1969).

Table 2. The frequency of mild goiter in Tatarstan in 1981/1985 (A) and 1986/1990 (B).

The Problems of Endemic Goiter Prophylaxis in Ukraine

V. A. Oleynik and A. D., Bely, Institute of Endocrinology and Metabolism, Kiev.

Lvov, Ternopol, Ivano-Frankovak, Chernovtsy, Transcarpathian, Rovno, and Volyn regions are endemic goiter regions in Ukraine. Severe areas of endemia were observed in the mountainous districts of Chernovtsy (Vizhnitsa and Poutila districts), Ivano-Frankovsk (Kosov and Zhabyev districts), and Transcarpathian regions (Veliko-Bereznyansk, Svalyava and Rakhov districts); an examination carried out there in 1941-47 revealed more than 50% of patients with goiter and 3% with cretinism. The iodine level in water did not exceed 1-2 mg/l.

In the 1950's, examination of the iodine content of subsoil water, soil and food in non-endemic regions revealed iodine deficiency in the following regions: the Crimea (Kuibyshevsk and Alushta districts), Donetsk (Kramatorsk and Slavyansk districts), Chernigov (Koryukovka district), Lugansk (Lisichansk district), Sumy (Shostka district), Kiev (Ivankov, Makarov districts), and Zhitomir (Yemelchinsk and Novograd-Volynsky districts). Thyroid size was increased in the population of these regions but the degree of endemic goiter was slight.

Prophylactic use of iodized salt in endemic goiter regions of the Ukraine began at the end of the 1940's. At first the content of iodine was 10 grams KI per one ton of salt (1:100,000), then it was increased and at present the ratio of KI:salt is 1:40,000. The use of iodized salt introduced into practice as a prophylactic measure in Ukraine, led to a rapid decrease in endemic goiter. Thus, in Rakhov district of the Transcarpathian region the number of patients with III-V stage goiter decreased from 9.2% in 1946 to 1.5% in 1955 (Kmit GI, et al., 1959).

Further prophylaxis of endemic goiter in the Republic was carried our according to a following pattern:

Regular and extensive iodine prophylaxis in the Republic, combined with effective control of iodine supply in the endemic areas, led to a considerable decrease in the number of patients with large goiter and in the magnitude of the endemia. Unfortunately, elimination of endemic goiter as a mass disease by the end of the 1960's led to a slackening of attention to this problem on the part of the government, medical institutions and sanitary and epidemiological service. First, control of the iodine content in salt was loosened. Losses of iodine increase with lengthening salt storage, and when stored in places with high humidity. In recent years, endemic regions did not receive adequate supplies of iodized salt (in 1990 only 50% of the whole amount of salt sold in Ivano-Frankovsk region, contained iodine). Sometimes salt was transported after being poured directly into trucks (Lvov region). The number and frequency of iodine measurements in salt have been insufficient (in 1991 only 44 tests, mainly in trading storehouses, were made in Ivano-Frankovsk region within six months, and in Lvov region, 355 samples were tested in 1986 compared to 112 in 1990).

The country's difficult economic situation adversely affected the quality of prophylaxis. For example, the iodine-deficient region, Ivano-Frankovsk, received only nine tons of sea products in 1990 instead of the 30,000 tons planned, and the percentage of needed KI tablets delivered to this region was only 84.5%.

These findings may account for an apparent recent rise in the prevalence of endemic goiter in the Ukraine. For example, in the Volyn region the incidence of severe endemic goiter was 68.7 per 100,000 in 1980 but 138.7 in 1990. The same tendency was noted in the Transcarpathian region, going from 64 to 116 per 100,000 people, from 88.1 to 142.0 in the Ivano-Frankovsk region, and from 144 to 202 in the Lvov region.

Of particular concern is the increasing incidence of large goiters among the children from endemic regions: it grew up from 10 per 100,000 children in 1980 to 34 in 1990 in Volyn region, from 12 to 22 in Rovno region, from 6 to 20 in Lvov region, from 11 to 20 in Ternopol, and from 1 to 12 in Chernovtsy region.

These alarming data show the severity of the current status of IDD. Despite changes in population numbers, industrial expansion and intensification of agriculture from use of fertilizers, the extent of iodine deficiency in endemic regions of Ukraine attributable to ecologic factors remains virtually unaltered. According to Z. I. Fabri (1989), the mean iodine concentration was 1.4 mg/l in the rivers of the Transcarpathian highlands and only 1 mg/l in well water. It was also low in foothills, from 1.5 to 1.9 mg/l, but reached 4.5 mg/l in the rivers and 4.1 mg/l in well water from low-lying lands. Comparative values between the mountainous zone of this region and the lowland were an average iodine level in milk of 2.0 mg/l vs 3.6 mg/l, in cabbage 5.1 mg I/% vs. 8.6 mg/%, and potatoes 4.5 vs. 6.8 mg/%. The lower iodine content in water and food stuffs in mountainous districts of the Transcarpathian region was confirmed by measurement of iodine excretion in urine: it was 32.4 ± 1.61 mg/day in healthy schoolchildren from the highlands, compared with 46.5 ± 3.61 mg/day in children from low-lying lands (p < 0.05).

We conclude that a reduced efficacy of prophylaxis in the Ukraine resulted in an increase in goiter prevalence. Only iodized salt should be permitted in the endemic goiter regions and proper transportation and storage of salt must be ensured. Penalties should apply to those who sell salt with an insufficient amount of iodine. Potassium iodate should be considered in place of the less stable potassium iodide to reduce iodine loss during storage. Iodine prophylaxis should be more vigorous in the mountainous areas than in the lowlands. If necessary, additional iodine should be provided in the form of KI supplements, its dose being determined by urinary iodine measurement. Endemic regions of Ukraine must be given priority for supplies of fish and other sea products. Regular clinical assessment should be carried out to monitor the efficacy of the prophylactic program.

Iodine Prophylaxis of Endemic Goiter in Uzbekistan

Y. K. Turakulov, Institute of Endocrinology, Tashkent, Uzbekistan.

Iodine deficiency appears to be the most important etiologic factor in the development of endemic goiter, as shown by the results of endemic goiter prophylaxis in this and other countries. Deficit of iodine in soil and water leads to its decreased ingestion with food and impaired synthesis of thyroid hormones.

The territories of Uzbekistan, Tadzhikistan, and Kirghizstan, especially certain places in the Ferghana valley and some valleys in the Pamirs, have been known for a long time as areas of severe endemic goiter. Both iodine prophylaxis, carried out in these areas on a regular basis since the 1950-1960's, and a marked improvement in socioeconomic and health conditions should favor the elimination of endemic goiter from this vast territory. However, IDD persists in all risk areas, despite preventive measures that include fortification of edible salt with 25 g potassium iodide per metric ton of salt and treatment of children of preschool and school age, as well as some other groups of the population, with antistrumin (1 mg tablet of KI once a week).

Table 1 shows the goiter prevalence in different parts of Uzbekistan. The overall prevalence was 5.5% for preschoolers, 12.2% for prepubertal, 16.5% for pubertal, and 23.1% for adolescents, for a total of 14.8% (21.4% for females, 8.0% for males). The severity of endemic goiter decreased considerably since the 1950-1960's, when universal iodine prophylaxis was started. However, mild goiter remains widespread despite these preventive efforts, although larger goiters are rare. This persistence requires further studies on the pathogenesis and molecular mechanisms of goiter development and elucidation of the possible role of other factors, besides iodine deficiency, in the etiopathogenesis.

Possible goitrogenic factors include a decrease and imbalance of trace elements in food, unfavorable soil and geographic conditions, other environmental influences, and malnutrition. However, there are no reliable data on the iodine content of foods or the environment in many regions. From the few determinations available, urinary iodine excretion has been reported to vary from about 100 mg/24 hours or more in nonendemic territories to less than 50-70 mg/24 hours in iodine deficiency areas. These results were confirmed by our studies. Specifically, children in Tashkent had a mean urinary excretion of 35.4 mg iodine per 24 hours

The daily iodine requirement is 100-300 mg of iodine per day, and the annual consumption of iodized salt is estimated at 3-5 kg/year (about 10 g per day) per capita. These figures provide a basis for calculating the amount of iodine to be added to cooking salt. The specified iodine levels should be monitored at production, distribution, and consumption as well as during storage and transportation of the packed product. Analysis of salt sold in different regions of Uzbekistan during the last five years showed that its iodine content differed from the mandated level in more than 60% of samples.

Table 1. Prevalence of endemic goiter in children (0-14 year old) living in different regions of Uzbekistan, 1987-1990.

IDD and its Monitoring in the Areas of China Neighboring the Former USSR

T. Ma, J. C. Li, F. F. Lin, Institute of Endocrinology, Tianjin Medical College, National Endemic Diseases Control and Research Center, and Institute of Endemic Diseases Control and Research of Xinjiang.

The iodine deficiency disorders (IDD) are a very significant problem in China. Almost 1/3 (370 million) of China's 1.1 billion population live in areas at risk for IDD. Among the 31 provinces, autonomous regions and municipalities of China, only Shanghai Municipality has no IDD problem. Before the iodization program, China had 35 million subjects with endemic goiter and now 8 million still remain. More than 250,000 are typical endemic cretins, and this number is increased several fold when we include the so-called "subclinical cretins."

Heilongjiang province, Nei-monggol Mongolian Autonomous Region, Jilin province, and Xinjiang Uygur Autonomous Region are the areas in China bordering the former USSR. IDD is very severe in the areas of Heilongjiang and Xinjiang near the former USSR, but not in Nei-monggol and Jilin.

Heilongjiang province in the northeastern part of China is separated from Russia by the Amur and the Ussuri Rivers. Its topography consists chiefly of well watered plains. The black soil is rich in humus. A survey in 1978 showed that 22.4 million people lived in iodine-deficient areas, including 1.77 million with endemic goiter and 3,500 cretins, all of the neurological type. Mental retardation, hearing and speech defects and neuromuscular defects were very prominent, but dwarfism, and sexual underdevelopment were uncommon, and almost no myxedema was found. The inhabitants in Heilungjiang province are chiefly Hans and Koreans. Cretinism and goiter are very rare among the Koreans, probably because they eat sea kelp, but some Han and Russian inhabitants were cretins. Subclinical endemic cretinism occurs quite frequently. A largescale province-wide salt iodization program has been operating since 1978. Also, to prevent new cretinism, intramuscular or oral iodized oil had been given to all married women at childbearing age. The effects have been good. By the end of 1981, 95.7% of the iodine-deficient population was covered by the salt iodization program. The goiter rate dropped from 8.71 to 1.97%, thus meeting the goal of control.

The Xinjiang Uygur Autonomous Region is in the northwest of China, contiguous to the Kazakhstan, Kyrgyzstan, and Tajikstan republics of the former USSR. The Tien Shan mountains cut the province into two halves, forming two basins. The climate is continental - dry and windy with limited rainfall, especially in its southern part. Most of the farmlands are irrigated with melted snow. The population is principally Uygur and Kirghiz in the south and Kazakn, Mongolian and Hans in the north. A survey in 1986 showed about 1.16 million subjects with goiter and 6.6 thousand typical cretins. The situation was more serious in southern Xinjiang. Three prefectures, Aksu, Kashi and Hetan, had 1.06 million goiters, an incidence of 21.1%. In some areas the cretinism incidence was as high as 2%, mostly neurological, but some were typical myxedematous and others showed features of both types. The myxedematous cretins were clinically quite similar to those described by McCarrison in 1908 in Gilgit (400 km from Kashi). Mental retardation, impaired hearing, and neuromuscular defects were not severe, yet dwarfism, sexual underdevelopment and myxedema were prominent. The inhabitants of Southern Xinjiang can easily obtain rock salt low in iodine from the desert without cost. This situation complicates the salt iodization program, and IDD control is still very unsatisfactory there. IDD in Northern Xinjian is not as severe as in the south, and the salt iodization program is quite successful there. The cretins there are chiefly neurological.

Once the iodization program has been initiated, the most important issue is monitoring. Since 1989, China has set up 23 monitoring sites, each of about 10-20,000 subjects, distributed among the known IDD endemias. The assessments are carried out by the Institutes of Endemic Disease Control in the respective provinces and all data are analyzed in the National Endemic Disease Control and Research Center in Harbin. Also, all provincial institutes and prefectures have their own monitoring sites. In 1990 this monitoring network demonstrated that our iodization program has many shortcomings. We have looked at the following four monitoring measures:

We recognize that information collected randomly rather than at fixed monitoring spots is more objective, but such a program is more expensive and more difficult to administer.

Epidemiology and Control of Iodine Deficiency Disorders in Poland

M. Gembicki, Department of Endocrinology, University School of Medicine, Poznan, Poland.

The first information on the presence of goiter in some villages in the Carpathian Mountains region dates from 1757, and a paper on the incidence and epidemiology of goiter in southern Poland, published in 1898, was among the first endemic goiter publications in the world. In 1930 Tobiasz developed a map of goiter prevalence in Poland from examination of army recruits. It showed a prevalence greater than 20% in southern territories near Krakow and Lwow and led to the establishment in 1932 of a Commission for the Fight Against Goiter. A survey of the iodine concentration in drinking water showed an inverse correlation with goiter prevalence.

In 1935 salt was iodized (5 mg KI/kg) and distributed in the Krakow region, with subsequent reduction in goiter prevalence in this part of Poland from 15.6 to 3.56% by the time of the Second World War.

Salt iodization resumed again in 1947. Poland's geopolitical situation had now changed significantly, with loss of some territories of east Poland and addition of others in the west. The endemic region near Lvov is now in the Ukraine. In the west, Poland acquired endemic goiter in the Sudeten region. With the migration of about two million Poles from east to west and from the villages to the towns, as well as the changes in dietary habits, areas previously free of goiter, for example, Poznan and Warsaw, now became endemic regions.

In 1970 outpatient departments were established to investigate the degree of iodine deficiency disorders (IDD). From 1951 the concentration of KI in salt was 8 mg/kg for the central part of Poland and 12 mg/kg for the southern territories. In 1959 a new map of goiter distribution in Poland was prepared by Falkiewicz and Pacynski from Wroclaw. The incidence was greater than 20% not only in the south but also in the northeast. In 1972 the concentration of KI was lowered to 8 mg/kg and in 1980 the salt iodization was interrupted.

Under pressure from endocrinologists and pediatricians, iodization was initiated at the theoretical concentration of 20 mg KI/kg in 1986. Unfortunately, the techniques of iodization were primitive, the KI concentration was very unstable, and the distribution of this iodized salt was uneven. As the result of these features, the goiter prevalence grew to 40-50% in the Carpathian Mountain regions and goiter was now observed in newborns, especially in the south of Poland.

In 1983 the screening of newborns for congenital hypothyroidism by TSH estimation started in Warsaw and in 1984 in Krakow. The incidence of congenital hypothyroidism was 1:4828 in the Krakow region, similar to that in other European countries. Recently screening with TSH determinations has been organized in Poznan, too.

After the Chernobyl nuclear accident in 1986, a large research program for evaluating the influence of the radioactive contamination on the thyroid started in Poland, and iodine prophylaxis was given to several million children and adults. These investigations in the different parts of Poland showed a prevalence of goiter in the range of 14-62%.

Using the WHO classification of thyroid gland enlargement, we noted that in the Poznan region (Gembicki and colleagues) 27.5% of a group of 11,086 persons had goiter, and in children aged 4-16 years, the goiter prevalence was 20%. In Szczecin (Czekalski and colleagues) of 4,565 persons examined, 19.5% had goiter, including 13.5% in children. In Wroclaw (Zukowski and colleagues) 17.8% of 4,310 persons had goiter, 18.4% of children. In Bialystok (Kinalska and colleagues) 30.6% of 10,006 persons investigated had goiter, including 28.2% of children. In Krakow (Szybinski and colleagues) of 4,719 persons 46.3% had goiter, including 57.2% of children.

The prevalence of goiter in children aged 6-15 years in a few other areas investigated in 1989-1990 was: Nowy Sacz 62.1% (Rybakowa and colleagues); Kielce 36.0% (Sielecki and colleagues); Rzeszow 28.0% (Nizankowska-Blaz and colleagues); Tarnobrzeg 69% (Rybakowa and Soltysiak-Wilk); and Piotrkow 20% (Zientek and colleagues). Parallel to these investigations, the concentration of iodine in drinking water for the Carpathian Mountains was found to be 0-2 mg/l (Szybinski), for Sudeten region 2-7 mg/l (Ewy), for Piotrkow district 3-4 mg (Zientek) and for Kiecle 0-7 mg/l (Holynska, Szybinski).

These data indicate the magnitude of the goiter endemia. To approach this problem a Polish Council for Control of Iodine Deficient Disorders (PCCIDD) was organized in April 1991 and a preliminary program of prophylactic measures was presented to the Ministry of Health. The PCCIDD requested the Ministry to organize the large scale iodization of salt at a concentration of 25 mg KI/kg. With a salt consumption of about 5-10 g/day this gives a daily iodine intake of 125-250 mg. In 1991 this salt will be distributed to the most endemic areas in the south, inhabited by about 1/3 of the country's population. Next year the production of iodized salt will be sufficiently large for distribution in the regions with lower grade of iodine deficiency, and later in the whole country.

Poland is actively cooperating with ICCIDD and in May 1991 pilot studies of goiter prevalence were conducted in schoolchildren (aged 8-14 years) in Poznan, Bialystok, and Krakow, with the assistance of Dr. R. Gutekunst from Lübeck who evaluated the thyroid size by ultrasound and determined the concentration of iodine in urine. It was found that in Poznan, 110 out of 341 children had goiter (32.2%), in Bialystok, 216 out of 424 (50.9%) and in Krakow 74 out of 291 (25.4%).

Currently, the PCCIDD is preparing for similar studies of schoolchildren in at least one school of each voievodeship (a political district) for more precise evaluation of the prevalence of IDD in the whole country.

Epidemiology of Endemic Goiter in the Former Yugoslavia

Zvonko Kusic, Zagreb, Croatia.

Endemic goiter has been present in the territory of today's Yugoslavia since medieval times. Such goiters were documented in some 13th and 14th century frescoes in a Serbian monastery. Between 1884 and 1901, 6-16% of recruits from Bosnia and Herzegovina were unfit for Austro-Hungarian Army service because of goiter.

Before introduction of iodine prophylaxis after World War II it was estimated that about two million persons (10.5% of the population) had endemic goiter, with prevalences varying from 10 to 90%. Another six million people lived in the endemic areas and should be considered as a population at risk. There were about 20,000 endemic cretins and 2,000-4,000 deaf mutes. The resulting adverse effects on the general health and the mental and physical abilities of the affected population were enormous.

The most intensive foci were located on the banks of rivers and in deep valleys where iodine was washed away from the surface soil. Goiter areas comprised practically all mountainous parts of the country, particularly the Alps, regions subjected to intense glaciation. Goiter-free areas were found along the Adriatic coast and in the northeastern plains. The analysis of drinking water and various foodstuffs, supported by examinations of urinary iodine excretion, suggested that iodine deficiency was the principal etiological factor.

Between 1930 and 1941 iodine prophylaxis was started in some heavily affected areas and after World War II it was continued by distribution of iodized salt. These measures proved unsatisfactory mainly because the population from endemic areas could obtain much cheaper noniodized salt from neighboring nonendemic areas. It was concluded that regional prophylaxis was not an appropriate solution because of the severity of disease and the distribution of endemic areas throughout the entire country.

Mandatory iodine prophylaxis by iodination of all salt from human and animal use was introduced in 1953, one of the first of such programs in Europe. The level of iodination was 10 ± 5 mg KI/kg NaCl. Both the organization and control of iodination posed many financial and technical problems.

The program has been carried out in several steps over the years. Until 1954 salt was iodized with 5 mg and after that, with 10 mg of KI. Complete iodine prophylaxis was achieved by 1956. From 1957 iodization of salt for animal use was also introduced on a large scale. Hyperthyroidism increased temporarily at the beginning of iodine prophylaxis and then declined.

Goiter prevalence decreased very dramatically, especially in the most affected areas and for goiter stage II. In some villages in Serbia goiter prevalence in schoolchildren decreased in seven years from 90% to 15-20%. Endemic cretinism decreased concomitantly. Intellectual performance and scholastic achievements among children also improved. The frequency of goiter among schoolchildren was substantially reduced in northern Croatia (from 51-88% to 21-45%). The number of recruits unfit for army service also decreased drastically (from 289 in 1952 to 15 in 1983) as did the number of soldiers requiring goiter surgery in military hospitals (from 2989 in 1951 to 48 in 1983). Thirty years after the introduction of iodine prophylaxis in Yugoslavia it could be concluded that endemic goiter has been virtually eradicated as a public health problem and that no real risk of endemic cretinism remained.

However, some disturbing recent reports note a rather high prevalence of goiter among schoolchildren (Serbia 17%, Macedonia 23%, Croatia 25%, Slovenia 15%). Although these goiters are mainly stage IA, the prevalence of 10-30% fulfills the criteria for mild endemic goiter (2). Mild iodine deficiency is also suggested by a fairly high thyroid uptake of radioactive iodine in nongoitrous subjects in some parts of Yugoslavia, and a proportion of toxic adenomas that is higher than in iodine-sufficient countries. Additionally, recent urinary iodine excretion measurements in Yugoslavia showed mostly borderline values, e.g., a significant proportion of children in Serbia had urinary excretion of iodine less than 100 mg/g creatinine. Although the values along the coast of Croatia were over 200 mg l/g creatinine, 112 mg was measured in Zagreb. Finally, thyroid volume as determined by ultrasonic scanning in 13 year old schoolchildren in Zagreb was 10.2 ml, higher than in South Germany (9 ml) or in Sweden (4 ml).

Etiologic factors other than iodine deficiency, such as dietary goitrogens or vitamin A deficiency, have been suggested. The best example is the island of Krk in the northern Adriatic Sea, where the goiter prevalence is 33% among schoolchildren despite the seemingly adequate iodine intake (3).

The existing goiter prevalence probably results from a defective iodization program. In a recent analysis of 55 salt samples from all domestic manufacturers, 70% showed iodine contents lower than the prescribed amount (7.6 mg I/kg of salt or 10 mg KI). All samples from some manufacturers had a low iodine content (4). It was also discovered that people in some areas with high goiter prevalence use cheaper, noniodized salt from neighboring countries. Intensive investigations have also revealed that rural populations often use noniodized cheaper salt that is intended for animal use. Originally, it was mandated that all salt must be iodized but in 1973 the change of constitution omitted the part of the original regulation including animals. Because of that, the content of iodine in milk and dairy products decreased. The food industry has also often used noniodized salt for animal consumption. All these factors contributed to a significant decrease in iodine intake from salt. Together with the low iodine content of the local diet and perhaps some other factors in some areas, a high prevalence of goiter has reappeared.

Recently measures have been taken to ensure the proper iodization of all salt, both for human and animal use. Some experts believe that the iodine content of 10 mg per kg of NaCl is inadequate and should be increased to 20 mg as in some other countries. Recently, a comprehensive project has been initiated to obtain a reliable nationwide estimate of goiter prevalence and iodine intake in the population.

References

Iodine Supplements of Livestock and their Influence on the Iodine Supply of Humans

M. Anke and B. Groppel, Friedrich Schiller University, Jena, Germany.

The iodine supply of animals is mainly determined by their habitat and its distance from the oceans, their food and their intake of goitrogenic substances.

The importation of fish meal in Germany once guaranteed a sufficient iodine supply for farm animals. After this practice was stopped, extensive signs of iodine deficiency occurred in farm animals in the New Lands of Germany (formerly East Germany) (Groppel 1988). This result was intensified by the replacement of the fish protein with plant proteins, e.g., rapeseed meal, which were particularly iodine poor and also contained many goitrogenic glucosinolates. Frequent cases of human iodine deficiency also occurred at the same time, particularly in Thuringia, Saxonia and Saxonia-Anhalt. For example, in Suhl, 82% of 12 to 15 year old students had goiter on surveys in 1978.

To correct this problem the mineral mixtures for cattle and pigs were supplemented with 10 mg I/kg as potassium iodate, to prevent the iodine deficiency in farm animals and also to improve the iodine supply of humans through a higher iodine content in milk, dairy products, meat, innards and sausage. This approach was particularly appealing because iodine has a prophylactic effect against goiter in animals as well as in humans, and supplementing humans through animal products limits the danger of iodine excess.

The iodine supplementation of mineral mixtures for ruminants and pigs corrected the iodine deficiency symptoms completely within one year and improved the performance of the animals very significantly (Wenk, 1989, Heinrich 1989).

Effect of iodine supplementation of mineral mixtures on milk and dairy products - In a study of 16 Thuringian villages, whose weathering soils of the Triassic are particularly iodine poor, the iodine supplementation of mineral mixtures increased the iodine content of the milk from 17 to 53 mg/l. On the average, the iodine content of milk tripled at rates varying from 125% to 818%. Two years after iodine supplementation the average iodine content of milk in Thuringia was 88 mg/l, range 71-106 mg/l, and thus was five times greater than in 1985 (Anke et al. 1989). By 1989 the iodine content in the milk reached a mean level of almost 90 mg/l (Table 1). Related to dry matter, curd contained only slightly more than half of the iodine content of milk, and cheese only one quarter, attributed to the very limited binding of the iodine to casein. Since most of the iodine is inorganic, it separates with the whey. More iodine is probably lost during the maturation of cheese.

Influence of the iodine supplementation of mineral mixtures on innards, meat, and sausage - The iodine content of meat in Thuringia was previously < 100 mg I/kg dry matter, but increased to an average of 199 mg I/kg dry matter for cattle and 121 mg/kg in pigs after supplementation. There was a highly significant correlation between the iodine content of liver and meat of the same animal in cattle (r = 0.85) and pig (r = 0.78). Usually the liver and meat of pigs are poorer in iodine than are the same tissues of cattle, due to the application of iodine-containing preparations for the disinfection of cow teats and probably to the higher fat content of pork. Overall, the iodine content of meat was approximately doubled by the iodization of mineral mixtures.

The analysis of different kinds of sausage and roast meat shows the influence of both the iodine supplementations of feedstuffs and the iodization of cooking salt (Table 2). The seven kinds of sausages contained between 134 and 630 mg/kg dry matter. Due to its high fat content, Brunswick sausage contained the least iodine. Surprisingly, hot dogs proved to be the richest in iodine, with > 600 mg/kg dry matter. This high iodine content mainly results from including the thyroid gland in this kind of sausage. Roast mutton was found to be poorer in iodine than roast pork and roast beef. Sheep apparently receive less of the iodine supplemented mineral mixtures than do cattle and pigs, as shown by the values for roast mutton.

Iodine supply of humans after the iodine supplementation of mineral mixtures and cooking salt - All foodstuffs for humans that we measured contain less than < 1000 mg I/kg dry matter, except sea fish (Table 3). Lettuce, cucumbers, eggs, and carrots contain an appreciable amount of iodine, from 200 to 610 mg I/kg. In contrast, fruits, freshwater fish, potatoes, and particularly cereal products contain < 100 mg I/kg dry matter and thus contribute little to the calculated daily human iodine requirement of 150 mg/day (Hetzel 1986). The iodization of mineral mixtures and of packed cooking salt in Saxonia, Thuringia and Saxonia-Anhalt reduced the occurrence of goiter within one year, but the calculated daily iodine intake of adults was still low, remaining in the 50 mg range. The iodine in animal foodstuffs is probably utilized particularly efficiently and this may explain the rapid disappearance of goiter in this region of Germany. After reunification, the iodine consumption of adults in the New Lands was reduced by 10% due to the delivery of animals for slaughter and milk from the former West Germany.

Summary

The addition of 10 mg I to each kg of mineral mixtures for farm animals quadrupled the iodine content of milk and doubled that of meat and innards. This effect and the iodization of cooking salt (10 mg I/kg) have provided an effective goiter prophylaxis program in the New Lands of Germany (the former East Germany).

References

Iodization of Salt: Legislation in Europe

H. Bürgi, Medizinische Klinik, Bürgerspital, Solothurn, Switzerland.

The European Community is preparing legislation which will govern the manufacture and sale of iodized salt. Since trade monopolies of any kind are not tolerated in the Community, it is to be expected that individual national iodization programs relying on a state monopoly for the sale of salt (e.g., in Switzerland or Austria) will have to be modified. In the meantime, iodization of salt is still subject to national legislation and the following survey shows interesting individual differences. These data may be helpful in formulating future laws, eventually at the European level. Due to lack of information from some countries, the survey is incomplete.

Iodized salt: availability and enforcement of use - The sale of iodized salt is prohibited in a single country, Denmark. The sale of iodized salt is voluntary in a large majority of European countries, namely in Belgium (Arrêté Royal, April 25, 1990), Finland, France (Arrêté Journal Officiel, March 16, 1963), Germany (Verordnung über Speisesalz, June 1989), Greece (Code of Foodstuff and Beverages Article No. 38, Government Paper 1005/76 Part B), Ireland, Italy (Decree Official Gazette 42-2-1972, and Decree 28.1.1977 Official Gazette 28.1.1977 No. 26), the Netherlands (Governmental Decree 1968, modified 1982; compulsory enforcement reversed by court order 1984), Norway, Poland, Spain (Royal Decree 1424/83 June 1, 1983), Sweden, Switzerland (Lebensmittelverordnung Articles 9.3 and 329.2 and Interkantonale Vereinbarung über Salzverkauf 1975), and in the United Kingdom (Food Standards Committee Rep Dec 1949; Code of Practice No. 11; Food Labelling Regulations 1984).

The use of iodized salt is compulsory in some countries: Austria (BG Verkehr mit Speisesalz, Bundesgesetzblatt 12.6.90 Nr. 126); Bulgaria (compulsory in endemic regions only, Order of Council of Ministers Nr 18, February 1959); Czechoslovakia (CSFR State Norm CSN 580910 October 10, 1967); Hungary; Portugal (Decreto Dei 49.27/26 September 1969, Portaria 338/70 and 4/70, compulsory in endemic regions only); and Yugoslavia (Sluzbeni List, Pravlinik No. 22/63.

In view of current public emphasis on individual rights and liberties it will be increasingly difficult to maintain compulsory programs in the future. In the Netherlands two bakers in 1984 mounted a successful court challenge to the compulsory addition of iodide to bread and the addition is now voluntary.

Iodine compound, amount of iodine and type of salt iodized - The amounts cited below refer to part per million (ppm) iodine, and not iodine compound.

Potassium iodide (KI) is the preferred addition, namely in Austria (15 ppm iodine, all salt), Bulgaria (20 ppm, all salt), Czechoslovakia (25 ppm, all salt), Finland (20 ppm, household salt), Greece (50 ppm, household salt), Hungary (15 ppm), Ireland (25 ppm, household salt), Italy (15 ppm, household salt), the Netherlands (20 ppm household salt; 45 ppm baker salt), Norway (5 ppm, household salt), Poland (20 ppm, all salt), Portugal 11.4 ppm, all salt), Spain (60 ppm, household salt), Sweden (50 ppm, household salt), United Kingdom (10-12 ppm, household salt), and Yugoslavia (7.5 ppm, all salt).

Sodium iodide (NaI) - First used in France (maximally 15 ppm; minimal amount not stated; household salt packages of not more than 1 kg).

Potassium iodate (KIO3) must be used exclusively in Germany (15-25 ppm, household salt), and may be used as an alternative to KI in Spain (60 ppm, household salt). The iodine compound remains unspecified in Belgium (4-45 ppm, all salt).

Labeling instructions - Legislators also must consider whether they want to impose rules for labeling of iodized salt. In Belgium, packages must indicate the mg iodine per 100 g salt and the shelf-life. In France the salt must be labeled as "iodized table or kitchen salt" and no therapeutic benefit may be mentioned.

Summary - Legislation allows iodization of salt in most European countries. In many of these, iodized salt, even though available and legal, is used quite sporadically, is distributed unevenly, or contains iodine well below the stated amount. Control of iodine deficiency will require not only proper legislation but also heightened awareness by the salt manufacturers and the public.