Goiter and Iodine Deficiency in Europe. the European Thyroid Association Report As Updated in 1988 R

JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION

Official Journal of the Italian Society of Endocrinology

Volume 12 March 1989 Number 3

CONTENTS

Thyroid function tests in acute viral hepatitis: relative reduction in serum thyroxine levels due to T4-TBG binding inhibitors in patients with severe liver cell necrosis M.C. Pagliacci, G. Pelicci, D. Francisci, C. Giammartino, L Fedeli, G. Stagni, and I. Nicoletti 149

Insulin resistance in acromegaly: evaluation by studies of insulin binding to erythrocytes A.C. Lerario, W. El-Andere, B.L Wajchenberg, L.Y. Ohnuma, M.H. Rocha, and A. Andriolo 155

Intravenous dexamethasone and subsequent ACTH test in comparison with dexamethäsone oral test in the diagnosis of Cushing's Syndrome: a report of 20 cases S. Gämbardella, G. Tamburrano, A. Giaccari, S. Frontoni, A. Lala, V. Spallone, A. Barini, M.G. Felici, and G. Menzinger 163

Melatonin effects on prolactin secretion in pituitary-grafted female rats A.l. Esquifino, M.A. Villanua, C. Agrasal, R.J. Reiter, and J.A.F. Tresguerres 171 Immunoreactive thyroglobulin in sera and saliva of patients with various thyroid disorders: role of autoantibodies AJ. Van Herle, P.D. Rosenblit, TL. Van Herle, P. Van Herle, M. Greipei, and K. Kellett 177

CASE REPORTS Possible association of aldosterone producing adenoma and non-functioning adrenal tumor R. Sorna, I. Miyamori, A. Nakagawa, T. Matsubara, H. Takasaki, T. Morise, I. Kon-i, R. Takeda, and T. Kobayashi 183

Partially compensated hypoadrenalism presenting with persistent skin pigmentation EM Whitehead, A.B. Atkinson, D.R. Hadden, J. Weaver, and B. Sheridan 187 Male pseudohermaphroditism due to 17-hydroxylase deficiency A. D'Alberton, E. Reschini, T Motta, and A. Catania 193

Cyproheptadine may act at the pituitary in Cushing's disease: evidence from CRF Stimulation J.R. Tucci, K.J. Nowakowski, and I.M.D. Jackson 197

COMMENT Inductive effects of progestogens on aromatase activity in stromal cells of human uterine endometrium T. Yamamoto, K. Shiroshita, J. Kitawaki, and H. Okada 201

SHORT COMMUNICATION Raised plasma levels of atrial natriuretic peptides in Addison's disease F.P. Cappuccio, N.D. Markandu, M.G. Buckley, A.L. Sugden, G.A. Sagnella, and G.A. MacGregor 205

II CONTENTS (continued)

REVIEW ARTICLE Goiter and iodine deficiency in Europe. The European Thyroid Association report as updated in 1988 R. Gutekunst and P.C. Scriba 209

ANNOUNCEMENTS IV International Congress of Andrology 154 XXXII Symposium of the Journees Internationales Henri-Pierre Klotz d'Endocrinologie Clinique on Peptide Hormone Secreting Tumors 154 Giornate Endocrinologiche Pisane 162 International Symposium on Circulating Regulatory Factors and Neuroendocrine Function 162 IV Congress of the European Neuroendocrine Association 192 XIV European Symposium on Hormones and Cell Regulation 192 International Workshop on Multiple Endocrine Neoplasia, Type 2 208 International Symposium "Thyroid Gland, Environment and Autoimmunity 1989" 208 Satellite Meeting on Iodine and the Thyroid 208

IV J. Endocrinol. Invest. 12: 209-220, 1989

REVIEW ARTICLE

Goiter and iodine deficiency in Europe. The European Thyroid Association report as updated in 1988.

R. Gutekunst and P.C. Scriba Department of Internal Medicine, Medical University Lübeck, Federal Republic of Germany

INTRODUCTION country. For the older literature, the reader is referred This review is based on the report of the subcommit- to references (3, 4, 15, 18-31). tee for the study of endemic goiter and iodine defi• Albania: ciency of the European Thyroid Association (1-4). Epidemiologie information on the prevalence of goi• No information is available. ter and alimentary iodine supply is scanty for most Austria: European countries. Although regional data are Iodine Prophylaxis has been mandatory since 1963. available, these do not necessarily reflect the Situa• Due to this, endemic cretinism had disappeared. tion throughout the country from which they origi• The incidence of hypothyroidism of newborn is nale. The regional data give relatively good informa• 1:4600, goiter prevalence in 6 years old 1.1-1.5%. tion concerning the population sample studied; Goiter prevalence rises with growing age up to however, it is frequently difficult to conclude which 13.4% in 18 years old. Up to 1 /3 of the adult popula• part of the whole population of a given area is re- tion have a goiter. Iodine exeretion in 2262 patients presented by the sample studied and which percen- from 5 cities show an iodine exeretion slightly below tage of the total inhabitants of the country live in the 100 jug iodine/g Creatinine. In Graz and Oberwölz, areas studied. Most surveys have used the Standard iodine exeretion is still below 70 ng iodine/g Creati• Classification of goiter size aecording to Pan Ameri• nine, though aecording to the decrease of radioio- can. Health Organization from 1974 (5), which is dine uptake from 52.4% in 1972 to 30.5% in 1981 associated with a signifteant risk of overestimation in (32) iodine intake must have improved. In Sicheldorf, children and underestimation especially in older a mean iodine exeretion of 132.6 iodine/g Creatinine adults as Sonographie volumetry has shown (5, 6-9). was found. Compared with the epidemiological data Daily urinary iodine exeretion or iodine exeretion before 1963, the Situation had drastically improved, from spot urine samples have widely been aeeepted however, a rise of potassium iodide from 10 mg to 20 as a satisfactory index of iodine intake (10, 11). mg/kg salt has been recommended and is in legisla• Since Europe, except one Spanish region (12), is not tive planning (33-37). considered to suffer from protein malnutrition, the urinary iodine/creatinine ratio is acceptable (13). Belgium: Hardly any data are available about potential effects A prevalence of goiter of 1.8% had been noted in of dietary goitrogens (14-16). Limitations of the study over 50.000 male army recruits in 1956 (18). A study of endemic goiter and iodine deficiency are partly on the seasonal Variation of stable iodine in non-tox- due to legal obstacles for epidemiology and the wide- ic goiter indicated a mean exeretion of 50 jLtg io• spread disinterest in iodine supplementation pro- dine/g Creatinine. Data from the 1960th indicate grams of European health administrations (17). similar figures (19, 38-42). In 1986, the median Information on goiter prevalence (Fig. 1), iodine urinary iodine concentration (jug/dl) in 196 healthy supply (Fig. 2) and supplementation programs (Ta• full-term infants born in Brüssels was 4.8 and thus ble 1) is listed in alphabetic order for each European lowerthan in Helsinki, Finland (11.2), but higherthan in Göttingen, FRG (1.5) (43). New and methodologi- cally reliable data on goiter prevalence and iodine supply are urgently needed. Key-words: Goiter, endemic goiter, iodine deficiency, thyroid. Bulgaria: Correspondence: Dr. Rainer Gutekunst, Dept. Internal Medicine. Medical University Lübeck Ratzeburger Allee 160. D-2400 Lübeck 1. West Ger• In 1957 a survey of 1 million schoolchildren revealed many. a goiter prevalence of 19.2%. First, iodized salt be-

209 R. Gutekunst and P C. Scriba

came mandatory only locally (20 mg Kl/Kg salt). GOITER PREVALENCE % Meanwhile, iodized salt is generally used in the whole country. In 1974, a reduetion of the regional goiter prevalence from 55 to 12% was reported for adults (44). In schoolchildren, goiter prevalence decreased to 8.5% in the district of Gabrovo and to 10.7% in Sofia in 1983 (45). One tablet containing 0.5-1.0 mg iodine is given weekly to every youngster up to the age of 18 years in endemic areas.

Czechoslovakia: The prevalence of goiter of 50% (m) and 70% (f) was observed in more than 370 persons examined between 1947 and 1953 (45), before the introduetion of iodine Prophylaxis. Correlation to low iodine exere• tion and to thioeyanate from brassica (16), respectively, was shown. Detailed data on the prevalence of diffuse and nodular goiters and of different sizes of goiters in men and women aecording to old districts during the years 1949 to 1953 have been published (46, 47). Iodine Prophylaxis was started in 1947 in some selected areas only, but since 1953 it was introduced in the whole territory. At that time, the content of potassium iodide was 12 mg/kg, but in some areas 25 mg/kg were used. Since 1965,18 mg

Fig. 1 - Goiter prevalence in percent; updated map of the ETA (2). l/kg salt is used in the whole territory. It is being Regional values are denoted by brackets. considered to increase the level up to 35 mg/kg after 1985. In 1966, follow-up studies in 100.000 subjects showed urinary iodine values having increased to 100 /^g/24 h and age-dependent de-

Table 1 - Status of iodine Prophylaxis

No endemic goiter Intermediate Belgium V Austria m Denmark n Bulgaria m Finland m Czechoslovakia» m Iceland — Hungary m Ireland V Netherland m Norway V Poland m Sweden m Switzerland m United Kingdom n Yugoslavia m

Endemic goiter No information FR Germany V Albania — France V Luxemburg — German DR m Soviet Union — Greece V Italy V Portugal V Romania _ Spain V Turkey —

Fig. 2 - Urinary iodine exeretion (fJtg/g Creatinine); updated map of m = mandatory or used by the vast majority; v = voluntary; n = none; — = no the ETA (2). Regional values are denoted by brackets. information.

210 Goiter and iodine deficiency in Europe

creases of goiter prevalence reported as an RT- Federal Republic of Germany: value of 110, which Stands for relative thyroid weight In 1984, thyroid size of more than 3000 school child- given in percent with RT=100 being normal (48). ren and more than 3000 adults from 25 and 10 The iodine Prophylaxis was interrupted for almost 7 German towns respectively were measured by so- years in 2 districts, which clearly showed and in- nography. These data of several authors (6-8, 55- crease of radioiodine uptake by the thyroid, a rise of 58) reveal a prevalence of enlarged thyroid glands in serum-TSH, and a decrease of urinary iodine exere• all age groups of approximately 40%. The iodine tion from 109.0 to 33.3 mg/24 h (district BK) and a exeretion from jspot urine samples amounts to 60/ig PBI in serum (30, 49, 50). l/g Creatinine. In neonates, iodine exeretion was Baby foods were sampled in two series - first from between 1.7 and 2.7 /ig/dl and thus 3 to 4-fold lower February 1977 to January 1979 (46 samples) and as compared to Swedes. Furthermore, alterations in second from February 1981 to October 1982 (79 Sonographie echopatterns were found in almost samples). In series one, the content of total iodine in 16% of the healthy adult population (6-8,55-58). The pure milk foods ranged between 20 and 40 jucg/l in iodinated salt (15-25 mg I /kg) is used on a voluntary 6.1%, 40 and 70 /ig/l in 72.2%, 70 and 100 jug/l in basis by less than 1 /3 of the population. Since this 12.1 %, and 100 and 150 /ig/l in 9.1 %, respectively. salt is only available as additional table salt, and In the second series, the total content of iodine since the mean use of salt was shown to be 1.7 g per ranged between 20 and 40 /ig/l in 6.1%, 40 and 70 day and person, the iodination program has not /ig/l in 24.5%, 70 and 100 /ig/l in 36.7%, 100 and pröven to be effective enough (59, 60). Since com- 150 /ig/l in 30.6%, and above 150 /ig/l in 8.2%, pulsory iodination of all salts used is legally not pos- respectively. The total iodine content in mixed foods sible, alternatively a gradual increase of iodine con• resembled that of pure milk foods. None of the sam• tent upto 50 mg I/kg table salt and/orageneral use ples exceeded 70 /ig l/l (51). of iodized salt in food produetion are recommended In 1985, thyroid volume was examined by ultrasono- (4). Programs to increase public awareness have graphy in 207 boys and 220 girls aged 15-16 years been started. from East Slovakia. 49.3% of the boys and 52.3% of the girls respectively had slightly enlarged thyroids Finland: between 10 and 15 ml. These thyroid volume re- Endemic goiter has declined to less than 6% (61). semble those found in areas of mild iodine deficien• Iodized salt is voluntarily but widely used. Milk prod- cy (i.e. FRG) and are twice as large as those reported uets are further iodine sources (62). The average from Sweden, where iodine intake is sufficient. Forty dietary iodine intake amounts to 340 /ig/d/person years of goiter Prophylaxis with iodized salt abol- (63). Earlier reports of goitrogens in milk have to be ished large and medium sized goiters in all age remembered (64, 65). groups and increased the urinary iodine exeretion to France: approximately 100 /ig/24 h. However, goiters grade Endemic goiter was reported from the Pyrenees. I are still endemic (52). Aecording to the older literature (1937) there were several areas of endemic goiter in France. In 1982 Denmark: the examination of 36,308 children from 13 districts In 1969, a nation-wide Screening of 6000 young men showed a goiter prevalence of up to 16.7%. Spot revealed a mean urinary iodine exeretion of 64 /ig urine samples (n = 3311) revealed a mean of 86 /ig I/24 h. The values were higher in Sealand (ränge 68 l/g Creatinine (66). A survey in Languedoc-Roussil- to 139) than in Jütland (ränge 41 to 28) (53). Aecord• lon including 3,157 ten to sixteen year old boys and ing to the ETA-questionaire 1981 and to personal girls revealed a goiter prevalence of 7.4% and a communication (P. Lauerberg), a committee under urinary iodine exeretion of 71.7 /ig l/g creatnine the Danish Health Department concluded from un- (67). published data on goiter prevalence in school children that iodine Prophylaxis was not necessary. Very German Democratic Republic: recent data from Funen showed an estimated daily In the last decade several epidemiological surveys urinary iodine - based on extrapolations from five were carried out in the GDR. All studies indicated hour collections in 505 subjects - of 76 /ig/24 h for that goiter prevalence was higher than 12% in the adult women, 89 for men, and 85 for the whole popu• whole country in all age groups increasing from lation, respectively. The median iodine exeretion North to South. Iodine exeretion was often found to was 58.8 /ig/9 Creatinine (54). The iodine exeretion be less than 50/ig I /g Creatinine. Iodized salt (unrel- for men was 77% higher than reported in 1969. iable and unstable content 5 - 25 mg Kl/kg) was Further information is lacking. used by less than 1 /3 of the whole population. By

211 R. Gutekunst and P C Scriba

1985, eighty-four percent of all table salt was iodized Adige, the prevalence of goiter was 9.2 to 37.9% by the more stable iodate (32 mg KI03/kg). Urinary amoung 3, 109 school children, whith regional iodine exeretion increased from less than 30 /ig in values of iodine exeretion between 4.57 and 18.5 1985 to more than 60 (ig in 1987. Goiter prevalence /ig/g Creatinine in 1982. In Tuscany, thyroid enlar- in newborns decreased below 1 %. In January 1988, gement was found in 63% of school children and mandatory use of iodinated salt has been intro- 83% of adults. TG-concentrations increased and duced. An interdiseiplinary iodine commission was serum TSH-Ievels decreased with goiter size. Func- established to control and coordinate necessary fol- tional autonomy of the thyroid was assumed for the low up studies (68-72). findings of low serum TSH (88).

Greece: Luxemburg: Endemic goiter remains common with prevalence Aecording to health authorities, there is no need for figures as high as 50% in some areas. Iodized salt iodized salt. The iodination of salt is not permitted by (40 mg Kl/kg) is available but more expensive than law. Data on goiter prevalence are lacking. non-iodized preparations. They are mainly used by the urban population, but not in the rural areas where The Netherlands: ID prevails. Urinary iodine exeretion in Athenians Endemic goiter has decreased since iodization of has increased to 94,5 /ig I Ig Creatinine in 1982 (24, breadsalt became mandatory in 1968 (46 mg Kl /kg). 73). In 1976 it became clear that the goiter Prophylaxis was insufficient. Based on the "Report of the Na• Hungary: tional Health Committee Goiter Prophylaxis" the io• A decrease of goiter prevalence from 32 to 11 % in dine content of breadsalt was increased to 60 mg schoolboys from some iodine deficiency areas was Kl /kg and iodized table salt (25 mg Kl /Kg) for volun- reported in 1981. The iodine content of salt was tary use was reintroduced. Due to a supreme court subsequently increased. However, the supply of io• verdict the use of iodized bread salt is not mandato• dized salt is irregulär. From data of 69 newborns, it ry, but only recommended since 1984. Fortunately, was deduced that iodine deficiency may still prevail the use of iodinated bread salt has hardly decreased (3). so far (17). The median urinary iodine exeretion var- Iceland: ies in different areas between 96 jug/d up to 138 There is no endemic goiter. In 1960, urinary iodine /ig/dl. Goiter prevalence is generally below3% (2 -4, exceeded 300 /ig/day (74). 89-92). However, areas with endemic goiter still ex- ist. In Doetinchem a goiter prevalence of 35% was Ireland: found in women. Sixty percent of these women ex- Available figures date back to the 1970s and before. creted less than 100 /ig iodine per day. In 1985 the Goiter prevalence of 27% and 12% was reported in goiter prevalence in school girls in different regions female and male emigrants, respectively (24, 75). varied between 19-39% with a median urinary iodine Random samples taken recently from 411 outpa- exeretion of 110 /ig l/g Creatinine, and in boys the tients in Dublin hospitals showed a mean urinary goiter prevalence was lower (4-31 %) with an exere• iodine of 137.5 /ig/g Creatinine and a median of tion of 120 /ig l/g Creatinine (91). Locally occurring 110.0; 23.3% had iodine exeretion values below 70 goitrogens are discussed, causing the regional differ- /ig/g Creatinine (76). It is cautioned that these fig• ences in goiter prevalence. ures cannot be taken as representative of the total Irish population; however, they justify more careful Norway: investigation for iodine deficiency. No further infor• Recent information was gained from 6 towns in Nor• mation could be obtained. way where 20 to 70 year old people were examined. No endemic goiter could be found. The iodine exere• Italy: tion ranged between 147 up to 247 /ig I a day and Endemie goiter is widespread in Italy, especially in has not significantly changes since 1972. The high the mountain areas, while big cities and heavily pop- iodine intake is mainly due to feeding cows with ulated areas are apparently free of endemic goiter seaweed. Salt is iodized with 5/ig l/kg (13, 93-95). (77). Iodized salt is available in some regions although its useremains limited (78-87). In Sicily, 25 to Poland: 80% of the school children had goiter, before prophy- Goiter prevalence of 20-40% in adolescents was lactic programs through water iodination have been reported, despite the use of 8 mg potassium iodide carried out in Troina, Sicily, resulting in a nearly per kg salt. After 20 years of Prophylaxis with current- complete goiter eradication in 1982 (87). In Alto ly 5-12 mg Kl per kg salt, the goiter prevalence

212 Goiter and iodine deficiency in Europe

ranges between 31 and 50 % in southern parts of ter and 46% had urinary exeretions of less than 50 Poland as the Carpathian Mountains and Cracow. /ig. In the Las Hurdes region, goiter prevalence of Eastern parts of Poland were heavily affected in 86% was found in school children. In this area creti• 1967 (45, 96). New data are lacking. nism still persists. Prophylaxis with iodized oil has been introduced in this region (12, 102). A thorough Portugal: review about iodine deficiency and goiter epidemi- Most of the population of Portugal lives near the ology has recently been issued by Francisco Es- coast, where no endemic goiter is found. Several cobar del Rey (Endocrinologia [Barcelona] 34, regions of the interior are severely affected. Prophy• Suppl. 2,1987). laxis with iodized salt (20 mg Kl/kg) in one area in Castel Branco started in 1971 reduced the goiter Sweden: prevalence in school children from 51% to 9,3% by There is probably no endemic goiter in Sweden. Salt 1977, whereas in another region of this district goiter has been iodized (50 mg/kg) for more than 10 years, prevalence in school children approximated 40%. In starting with 10 mg/kg in 1930 and rising to 20 Portalegre, Baixo Alentejo and Algarve, goiter en- mg/kg in 1940. Commercial baby diets are iodized. demia goes up to 54%. Some endemic cretinism was Foods used for animals are iodized. In Stockholm, a reported (2-4,97, 98). Since 1981, iodized table salt median iodine exeretion of 141 was found in adults (60 mg Kl/kg) is available but not mandatory and and 124 /ig/g Creatinine in 13-years old. Swedish rarely used, particularly in rural areas. neonates showed a two- or three- to four-fold medi• Surprisingly , in the island of S. Miguel (the Azores) an urinary iodine exeretion, when compared to the prevalence of goiter in school children varied Swiss or Germans, respectively. The median thyroid between 11 and 41%. In the most affected region, volume of adults and 13-years old, respectively, as 16% of the adult males and 48% of the women had estimated by sonography was twice as small, when goiter. The median urinary exeretion of iodine varied compared with those found in the iodine deficient between 10 and 49 /ig l/g Creatinine (99). Germany(6-9, 43, 55). Further mappings of iodine Romania: exeretion and goiter prevalence figures are lacking. A regional prevalence of more than 60% is reported Switzerland: for the Carpathian Mountains in 1980. Antiendemic I n 1975, a survey showed a goiter prevalence of 20% centers have been organized in all endemic regions in adults aged 20-39 and of 60% in the 60-79 age during 1949 -1978 period (100). Iodized salt for the group. The higher figures in the elderly reflect inade- population and, in addition, iodinated tablets for quate iodination of salt before 1980 (103-105). In school children and pregnant women, have been 1983, a goiter prevalence of only 1% was found in used (43, 100). In 1986,20,000 children from Mures 19-year old male army recruits. The potassium Jo• county representing 91.2% of all enlisted 6-14 years dide content of table salt has been increased pro• old were examined. Goiter was found in 16.8% (62). gressive^ over the last two decades to now 20 Soviet Union: mg/kg. Iodination of all salt for huaman consump- No information about the European part of the Soviet tion (includes salt for food Industries and restau- Union has been obtained. An endemic area of Us• rants) is practically mandatory (106). In 1983 the bekistan with iodine deficiency goiter was described mean iodine exeretion was 141 /ig per day (107). (101); subjects in this area reeeive 1 mg iodine per Turkey: day as Prophylaxis. Endemie goiter is a problem at the Black Sea,shore Spain: and in the inner parts of Eastern and Western Anato- Several surveys from this decade have been pub- lia. In some provinces such as Bolu, Bursu, Isparta, lished. In Galicia, 2,872 school children revealed a Kastamonu, Rize and Trabzon, goiter prevalence 79% prevalence of goiter with 85% exereting less exceeds 15%. In many provinces such as Adiya- than 25 /ig l/l urine. From Andalusia the goiter pre• man, Artvin, Bilecik, Bingöl, Burdur, Canakkale, De- valence of 4,949 school children was 29%; 40% had nizli, Eskisehir, Gümüshane, Izmir, Kars, Konya, Kü- an urinary iodine exeretion of less than 40/ig l/l. In tahya, Malatya, Mardin, Mus, Sakarya, Samsün, Sin- Catalonia, a population sample from 255 rüral com- op, Sivas, Tokat, Yozgat and Zonguldak, goiter preva• munities showed a goiter prevalence of 35,8% and a lence is 5-15%. The nation-wide detailed investiga- mean exeretion of 79/ig l/g Creatinine. In Asturias, tion on the prevalence of endemic goiter dates back 6922 school children had a goiter prevalence of 20% to the sixties. Urinary iodine exeretion was below 70 and a urinary iodine exeretion of 63/ig/l. In Guada• /ig l/g Creatinine (108-111). New data are urgently lajara, near Madrid, 58% of school children had goi• needed.

213 R. Gutekunst and P.C. Scriba

United Kingdom: take remains borderline and analysis of the iodine The average British diet provides 250 jug iodine a content of salt from three of these countries gave day. Milk is the most important individual source of values ranging from 4 to 12 mg of I/Kg salt (2). iodine but is also the most variable. Regional preva• Experience from other countries in which iodine lence of goiter reported in 1924 does not permit Prophylaxis is mandatory has shown that iodine con• epidemiologieal conclusionsfor today. There is little tent of salt must be at least 20 mg/kg (preferable in evidence that major areas of endemic goiter persist the stable form of KI03) to meet the WHO recom- (112-116). mended iodine intake (150-300 jug/d) in areas where there is little iodine in other components of the Yugoslavia: diet. Persisting regional prevalence of endemic goiter up to 25% and the mandatory use of iodized salt (10 mg - Iodine Prophylaxis not mandatory Kl/kg) since 1956 have been reported. Defects in This large group consists of the Federal Republic of iodizing techniques and/or loss of iodine from the Germany, France, Greece, Italy, Portugal, Romania, salt are considered to be responsible for the incom- Spain, and Turkey. Goiter continues to be a major pleteness of goiter eradication (15). Further informa• problem in these countries, either nationwide or re- tion is lacking. gionally. Iodine intake is so low in some regions that the risk of cretinism persists. Effective iodine Prophy• DISCUSSION laxis programs are urgently required in these coun• tries. The data reported above are not uniform; variations between countries represent methodological differ- Adequate information unobtainable ences, incomplete information and, in some instan- Albania, Luxemburg and the USSR. ces, failure to use the generally accepted Classifica• tion of thyroid size. Although these data are incom• CONCLUSION plete, the report elucidates the present Status of The data of this survey provoke concern rather than endemic goiter and iodine intake in Europe and complacency. More epidemiologieal studies, includ- urges for further surveys. Obviously, goiter remains ing studies of other goitrogenic mechanisms (117- a significant problem (Table 1). 119) and comprehensive iodination programs are No endemic goiter urgently needed. Such programs have to be moni- This applies for Iceland, Norway and the United tored for their effectiveness. Any iodine-induced hy- Kingdom. Belgium, Denmark, and Ireland, though perthyroidism due to an increased prevalence of borderline ID, probably also belong to this group. In thyroid autonomy or immunogenic effects have to Sweden, and Finland highly effective goiter Prophy• reeeive adequate attention (120-132). Furthermore, laxis programs have been established. These coun• the daily intake, as well as the quality and standardi- tries define the goal which can and should be zation for iodized salt preparations must be checked achieved elsewhere in Europe. carefully (133-139). In a recent study, the iodine content of 104 commercial salt samples from 19 Intermediate European countries was analyzed. The results This group comprises Bulgaria, Czechoslovakia, showed that iodine content was significantly lower The Netherlands, and Switzerland. These countries than that intended by the manufacturer in approxi• have had major problems with endemic goiter in the mately 30% of samples (2-4). past, but have introduced goiter prevention pro• In the newborn, iodine deficiency causes transient grams. Epidemiologieal surveys have shown that effects on thyroid funetion and increased suseepti- endemic goiter persists in some adults in these bility to the toxic effects of acute iodine loads (55, countries, but that it is hardly seen in children. 140, 141). The increased frequency of elevated thyrotropin levels in Screening programs for congen• Endemic goiter persists ital hypothyroidism may also be regarded as a sensi• This group contains 13 countries - 50% of the total in tive index for iodine deficiency (142). this review. The German experience suggests that the Societies - Iodine Prophylaxis mandatory for Nutrition may be more successful than endoeri- This sub-group consists in Austria, The German nologists in persuading health authorities to intro- Democratic Republic, Hungary, Poland, and Yugosl• duce iodine Prophylaxis. In addition, it should be avia; substantial areas of high goiter prevalence remembered that permission and recommendation persist despite iodine Prophylaxis. Dietary iodine in• to use iodized salt in preprepared food as bread,

214 Goiter and iodine deficiency in Europe

sausages, cheese etc. can be particularly success- 9. Gutekunst R., Scriba PC. ful as experienced in Bulgaria, Finland, the German Iodine deficiency disorders in Europe. Democratic Republic, Sweden and Switzerland. In: Hetzel BS, Dunn J.T., Stanbury J.B. (Eds.), The Notably, the aedequate iodine intake in Finland, Prevention and Control of Iodine Deficiency Dis• Norway and the United Kingdom is at least partly due orders. to an inadevertently high iodine content of the milk, Elsevier, Amsterdam, 1987, p. 249. which might be subject to undesirable modification 10. Jolin T., Escobar del Rey F. in the future. Evaluation of iodine/creatinine ratio of casual sam• ples as indices of daily urine iodine Output during field Considerable sums are spent on the diagnosis and studies. treatment of goiter by public health Systems or insu- J. Clin. Endocrinol. Metab. 25: 540,1965. rance companies in many countries -more than 500 11. Oddie T.H., Fisher DA, McCohaney W.M., Thompson million US-Dollars in 1987 in the Federal Republic of CS. Germany (143, 144). Prevention is straight forward Iodine intake in the United States. A reassessment. and cheap. J. Clin. Endocrinol Metab. 30: 659,1970. 12. Escobar del Rey F., Gomez-Pan A., Obregon M.J. A survery of schoolchildren from a severe goiter area in Spain. REFERENCES Quart. J. Med. 50: 233,1981. 1. Delange F., Bürgi H. 13. Frey H.M., Rösenlund B., Torgersen J.P. Iodine deficiency disorders in Europe. Value of Single urine speeimens on estimation of 24 17th Annual Meeting of the European Thyroid Asso• hour urine iodine exeretion. ciation and WHO Bulletin, 1989, in press. Acta Endocrinol. (Kbh.) 72: 287,1973. 2. Scriba P,C, Beckers C, Bürgi K, Escobar del Rey F., 14. Ingenbleek Y., Luypaert P., DeNayer P. Gembicki M., Koutras D.A., Lamberg B.A., Langer P., Nutritional Status and endemic goiter. Lazarus A„ Querido A., Thilly C, Vigneri R. Lancet 1: 388,1980. Goiter and iodine deficiency in Europe. Report of the 15. Matovinovic J. Subcommittee for the Study of EndemicGoiter and Endemic goiter and cretinism at the dawn of the third Iodine Deficiency of the European Thyroid Associa• millennium. tion. Ann. Rev. Nutr. 3:341,1983. Lancet 7:1289,1985. 16. Podoba J., Langer P. 3. Scriba P.C. Naturally occuring goitrogens and thyroid funetion. Goiter and iodine deficiency in Europe - a review. Bratislava, Slovak Academy of Sciences, Pub. 1964, p. 1. In Reinwein D., Scriba P.C. (Eds.). Treatment of en• 17. Bundesministerium für Jugend, Familie, Frauen und demic and sporadic goiter. Gesundheit. Stuttgart, Schattauer, 1985, p. 19. Rechtliche Regelung für jodiertes Speisesalz und 4. Scriba P.C., Gutekunst R. Hötzel D. seine Verwendung in Lebensmitteln. Probleme der Jodprophylaxe. Ergebnis einer Länderumfrage, 1987 Verh. Dtsch. Ges. Inn. Med. 92: 263,1986. 18. Brüll L, Dewart L 5. Dunn J.T., Medeiros-Neto G.A. Repartititon et frequence du goiter chez les recrues Endemic Goiter and cretinism: Continuing threats to en Belgique. world health. Rev. Med. Liege 11: 653,1956. Washington DC: PAHO Scientific Publication No. 19. Delange F., Ermans A.M. 292,1974, p. 1. Le metabolisme de l'iode ä la puberte. 6. Gutekunst R., Groth K., Scriba P.C., Windler B. Rev. Fran. d'Etude Clin. Biol. 72: 815,1967. Zur Kritik der Strumaepidemiologie (III). 20. Habermann J„ Heinze H.G., Horn K., Kantlehner R., Dtsch. Med. Wochenschr 708:1985,1983. Marschner l„ Neumann J., Scriba PC. 7. Gutekunst R., Smolarek H., Wächter W., Scriba P.C. Alimentärer Jodmangel in der Bundesrepublik Deut• Strumaepidemiologie. IV. Schilddrüsenvolumina bei schland. deutschen und schwedischen Schulkindern. Dtsch. Med. Wochenscher 700:1937,1975. Dtsch. Med. Wochenschr. 709: 50,1985. 21. Horster F.A., Klusmann G., Wildmeister W. 8. Gutekunst R., Smolarek H., Hasenpusch U., Stubbe Der Kropf: Eine endemische Frankheit in der Bundes• P., Friedrich HJ., Wood W.G., Scriba P.C. republik? Goiter epidemiology: thyroid volume, iodine exere• Dtsch. Med. Wochenschr 700: 8,1975. tion, thyroglobulin and thyrotropin in Germany and 22. Johnsson S. Sweden. Endemisk struma-frekvens i Medelpad. Acta Endocrinol (Kbh.) 7 72: 494,1986. Läkartidningen 62: 2049,1965.

215 R. Gutekunst and P.C. Scriba

23. Kelly F.C, Snedden WW. 36. Riccabona G., Glatzi J., Platzer S., Fill H., Ehlich P., Prevalence and geographica! distribution of endemic Obendorf L goiter. Gibt es noch eine Kropfendemie bei Ostereichs Ju• In: (Ed.) Endemic Goiter. gend? WHO Monograph Series No. 44, WHO, Geneva, Päd Pädol 16: 189,1981. 1960, p. 27. 37. Steiner H., Zimmermann G. 24. Koutras D.A. Die Epidemiologie der endemischen Struma unter Survey - Europe and the Middle East. Jodsalzprophylaxe. In: Stanbury J.B., Hetzel BS. (eds.). Endemic goiter Wien. Med Wochenschr. 128: 476,1978. and endemic cretinism. 38. Beckers C, de Crombrugghe, de Visscher M. Wiley, New York and Sans, 1980, p. 79. Le role de la carence en iod dans le goiter spora- 25. Lagasse R., Ramioul L, Yegers O., Thilly C.H. dique. Collaborative study of geographica! variations in thy- Ann. Endoer. 23: 238,1962. roidal uptake and iodine intake in Europe. 39. Beckers C, Delange F. ETA, 7th Meeting, Helsinki, 1976, unpublished. Iodine deficiency. 26. Malamos B., Miras K., Koutras D.A., Kostamis P., Bi- In: Stanbury J.B., Hetzel B.S. (Eds.) Endemic goiter and endemic cretinism. nopoulos D.t Mantzos J., Levis G., Rigopoulos G., Zerefos N., Tassopoulos C.N. Wiley and Sons, New York, '1980, pp. 199. Endemic goiter in Greece: Metabolie studies. 40. Beckers C, Noel A. J. Clin. Endocrinol. Metab. 26: 696,1966. Evidence for relative iodine deficiency during puberty. 27. Malvaux P., Beckers C, de Visscher M. J. Clin Endocrinol. Metab. 34: 414,1972. Iodine balance studies in non-goitrous children and 41. De Crombrugghe B., Beckers C, de Visscher M. in adolescents on low iodine intake. Channel aspects of iodine metabolism in sporadic J. Clin. Endocrinol; Metab. 29: 79,1969. goiter. 28. O'Donovan D.K. Acta Endocrinol. (Kbh.), 42: 300,1963. The problem of endemic goiter in Ireland. 42. De Crombrugghe B., Beckers C, de Visscher M. Ir.J. Med. Sei. 161:1950. Bilan du cycle i'iode chez des sujets thyroidiens non 29. Pflüger H. goitreux. Die geographiesche Verbreitung des Kropfes in Eu• Rev. Fran. d'Etude Clin. Biol. 9: 307,1964. ropa. 43. Delange F., Heidemann P., Bourdoux P., Larsson A., Dtsch. Arch Clin. Med. 180: 212,1973. Vigneri R., Klett M., Beckers C, Subbe P. 30. Podoba J., Stukovsky R. Regional variations of iodine nutrition and thyroid Thyroid funetion after stopping of iodinated salt distri• funetion during the neonatal periöd in Europe. bution. Biol. Neonate, 49: 322,1986. Acta Endoer. Panameric. 3:135,1972. 44. Bozadjeva E., Staikov T., Solakova V. 31. Thilly C.H., Ramioul L, Ermans A.M. The Screening of endemic goiter in Bulgaria. A collaborative study on the geographica! variations Proceedings of IV Balkan Congress of Endocrinol- of thyroidal uptake in normal subjects of Europe. ogy. Printing Office of Ankara University, 1986, p. 155. Eur. J. Clin. Invest. 3: 272,1973. 45. Langer P. Eastern and Southeastern Europe. 32. Goebel R., Leb G., Passath A., Knapp G. In: Stanbury J.B., Hetzel B.S. (Eds.) Endemic goiter Jod-123-Speicherwerte der Schilddrüse und Harnjo- and endemic cretinism. dausscheidung in einem Strumaendemiegebieti Wiley and Sons, New York, 1980, p. 141. Therapiewoche 33: 3530,1983. 46. Podoba J. 33. Galvan G., Balcke C, Giblitz J.H., Hauch D., Rücker Endemicka Struma na Slovensku. W., Maier F. Vydavatel'stvo Slovenskej Akademie Vied, Bratisla• Jodmangel in Salzburg trotz Jodsalzprophylaxe. va, 1962, p. 1. Wien. Klin. Wochenschr. 94: 609,1982. 47. Podoba J., Stuvkovsky R., Kovav R. 34. Galvan G. Thyroid funetion sibships in endemic goiter regton. Soll die Jodierung des Spesesalzes in Osterreich er• J. Clin. Endocrinol. Metab. 31:134, 1970. höht werden? 48. Silink K., Cemy K. Wien Med. Wochensch. 135: 71,1985. Endemic goiter and allied disease. Bratislava, Slovak 35. Lind P., Klima G., Wakonig P., Wawschinek O., Eber O. Academy of Sciences, Pub. Bratislava 1966, p. 1. Harnjodidausscheidung und Strumahäufigkeit in der 49. Podoba J. Steiermark - Untersuchungen 20 Jahre nach gesetz• Research report. licher Einführung der Jodsalzprophylaxe. Bratislava, Institute of Experimental Endocrinology, Acta Med. Austriaca 12: 45,1985. Bratislava, 1975.

216 Goiter and iodine deficiency in Europe

50. Podoba J., Reisenauer R. 62. Vasilescu G.H., Tofoianu I.H.G., Ismanscu I., Hirsch• Die Wirksamkeit der Jodprophylaxe in der CSSR. feld I., Horga M., Kun L, M.R. Maior., Ciobanu-Sonea In: Scriba P.C., Rudorff K.H., Weinheimer B. (Eds.), V., Reka Vancza, Dungaciu G.H., Babau D. Schilddrüse. Prevalence of endemic goiter in Mures County. Stuttgart, Thieme, p. 239. Rev. Roum Med. Endocrinol. 24: 27,1986. 63. Varo P., Saari E., Passo A., Koivistoinen P. 51. Görner F., Knopp J., Havelka B., Jakubco E., Pazitko- Iodine in Finnish foods. va A., Zigova Z. Int. J.Vit. Nutr. Res. 52: 80,1982. Dynamik obsahu celkoveho jodu v mliecnych pri- pravkoch pre dojcenecku vyzidu. 64. Lamberg B.A., Haikonen M., Makela M., Jukkara A., Sbornik Uvtiz - Potravinarske Vedy 19: 63,1984. Axelson E., Welin M.G. 52. Tajtakova M. Further decrease in thyroidal uptake and disappear- Thyroid volume of East Slovakian adolescents de- ance of endemic goiter in children after 30 years of termined by ultrasound 40 years after introduction of iodine Prophylaxis in the East of Finland. iodized salt. Acta Endocrinol. (Kbh.) 98: 205,1981. Klin. Wochenscher. 66: 749,1988. 65. Lamberg B.A., Haikonen M., Makela M., Jukkara A. 53. Munkner T. Wirksamkeit der Jodprophylaxe in Ostfinnland. Urinary exeretion of 127 iodine in the Danish population. In: Scriba P.C., Rudorff K.H., Weinheimer B. (Eds.) Scand J. Clin. Lab. Invest. 24: (Suppl. 110), 134,1969. Schilddrüse. Thieme, New York, Stuttgart, 1982, p. 248. 54. Haas V.f Marley M., Green A., Date J., Blichert-Toft M., Mogensen E.F. 66. Mornex R. Urinary iodine exeretion in a geographically stratified Goiter prevalence in France. Danish population sample not affected by iodination Bull. Acad. Natle Med. 171: 301,1987. programs. 67. Jaffiol C, Gebert M., Cailhol A., Baylet R., Baldet L, Acta Endocrinol. (Kbh.) 119:125,1988. Lachiver F., Chapate M., Mirouze J. 55. Heidemann P.H., Stubbe P., von Reuss K., Schnürn- Etüde approfondie complementaire d'une enquete brandt K., Larsson A., von Petrykowski W. epidemiologique realisee en milieu scolaire sur la Jodausscheidung und alimentäre Jodversorgung bei frequence du goiter et la carence iodee en Langue- Neugeborenen in Jodmangelgebietn der Bundesre• doc-Roussillon. publik. Bull, Acad, Natle Med. (171) 8:1095,1987. Dtsch. Med. Wochenschr., 109: 773,1984. 68. Bauch K. 56. Ulbricht T., Schmitka T., Meilinghoff U., Bencker G., Zur Frage des alimentären Jodmangels in der DDR. Reinwein D. Z., Gessante, Med. 39: 307,1984. Sonographische Bestimmung von Schilddrüsenvo• lumina bei Schilddrüsengesunden. 69. Bauch K., Grosse E., Seitz W. Dtsch. Med. Wochenschr 108:1355,1983. Untersuchungen zur Frage des Jodmangels während 57. Reiser H.H., Schmidt K.J., Rothenbuchner G., Labon- der Schwangerschaft im Strumaendemiegebiet. vie S. Dtsch. Gesundh-Wesen 39:1820,1984. Zur Häufigkeit von Schilddrüsenerkrankungen im 70. Bauch K., Anke M., Gürtler H., Hesse V., Knappe G., Bayrisch/ Baden Württembergischen Allgäu. Körber R., v. Kozierowski, Meng W., Thomas G. In: Pickardt CR., Schleusener H., Weinheimer B., Zur Entwicklung und Effektivität der Strumaprophy-' (Eds), Schilddrüse 1983. laxe in der DDR. Stuttgart, Thieme, 1985, p. 524. Z. Gessante inn. Med. 24: 714,1987, 58. Stubbe P., Heidemann P. 71. Meng W., Ventz M., Weber S., Bednar J. Struma neonatorum - blande Struma im Kindesalter. Struma und alimentärer Jodmangel in der DDR. Dtsch. Arztebl 80: 40, 1983. Dtsch Gesundheitswes 36:1275,1981. 59. Weber P., Manz F., Horster F.A., Kersting M., Klett M., 72. Meng W., Bauch K., Knappe G. Schöch G. Iodine deficiency in the GDR. Die Bedeutung von jodiertem Speisesalz, Milch und Endocrinol. Exp. 20: 79,1986. Milchprodukten sowie Fisch für die Jodversorgung. Ernährungs - Umschau 33, Heft 3, 99,1986. 73. Koutras DA, Katsouyanni E.K., Livadas D.P., Piper- 60. Weber P., Manz F., Kersting M., Schöch G. ingosr D.G., Tzonou A., Trichopoulos D. Jodsalzverbrauch und Kochsalzumsatz. An epidemiologic survey of thyroid enlargement Dtsch. Med. Wochenschr 111:1916,1986. among school children in a non-endemic area. Endokrinologie (Leipzig) 79: 349,1982. 61. Lamberg B.A. Endemic goiter in Finland and changes during 30 74. Sigurjonsson I. years of iodine Prophylaxis. Advance in thyroid research. Endocrinol. Exper. 20: 35,1986. Pergamon Press, Oxford, 1961, p. 279.

217 R. Gutekunst and P.C. Scriba

75. Greenwald I. 90. van Rees-Wortelboer M.M., Tan W.D., van der Heide The history of goiter in Ireland. D., Querido A. J. Irish Med. Assn. 68: 69,1975. Changes in goiter frequency and iodine exeretion 76. Smith P.P.A. after increased iodine supply. In: Hall R., Köbberling J. (Eds). Thyroid disorder asso- Personal communication, 1986. ciated with iodine deficiency and excess. 77. Lampertico P. Raven Press Serono Symposia, 22: 25,1985. Pathology of the thyroid gland in Italy: final remarks. Pathologica 74: 409,1982. 91. Van Rees M.M. Ned. Tijdschr. Geneeskd 131:1981,1987. 78. Bartalena L, Baschieri L, Ceccarelli C, Fenzi G.F., 92. Van Rees-Wortelboer M.M. Giani C., Lippi F., Macchia E., Monzani F., Pinchera AM Siclari C. Jodium en krop in Nederland. Een evaluatie van de II gozzo endemico in Toscana. Strumaprophylaxe. Salute e Territorio 24:18,1982. Thesis, Leiden, The Netherlands, 1988, p. 5. 79. Baschieri L, Costa A., Basile A. 93. Frey H.M., Rosenklund B., Storli U. II Gozzo Utskülese av jod i urinen i enkelte norske befol- Pozzi Pub., Roma, 1978, pp 80-87. kningsgrupper 1971 - 1972. Tidsskr. Nor. Laegeforen 94: 982,1974. 80. Costa A., Mortara M. Goiter. 94. Frey H.M., Tangen T., Lovik J. Thorsen K., Sand T., Panminerva Medica, 23:141,1981. Rosenlund B., Kornstad L. Endemisk struma eksisterer ikke lenger pa Modum. 81. Delange F., Vigneri R., Trimarchi F. Tidsskr. Nor. Laegeforen 101:1184,1981. Etiological factors of endemic goiter in Northeastern Sicily. 95. Kapelrud H., Frey H. J. Endocrinol. Invest. 2:137,1978. Utskillelse av jod i urinen. Tidsskr. Nor. Laegeforen. 107:1320,1987. 82. DeLuca F., Cramarossa L, Toneiii S., Benedetti G.A., Negri M., Baschieri L, Cassano C. 96. Falkiewicz A., Pacynski A. Iodine deficiency in two endemic goiter areas of Cen• Wolew Polsce. Goiter in Poland. Prace Wroclawskie- tral and Southern Italy. go Towarzystwa Naukowego Seria B, No. 147,1967.

J. Clin. Endocrinol. Metab. 26: 393,1966. 97. Lopes de Oliveira A.t Sobrinho L.G., Botelho LS., 83. Doveri F., Fenzi G.F., Siclari C, Bartalena L, Cecca• Oliveira P.A., Concalves M.J., Antunes M.T. relli C, Chiovato E., Macchia E., Pinchera A., Ba• Bocio endemico no sul de Portugal. schieri L. Med. Chir. 3: 269,1983. II gozzo endemico in.provincia di Pisa. Aspetti epide- 98. Sobrinho LG., Limbert E.S., Santos M.A. miologici e metodologia della ricerca. Thyroxine toxicosis in patients with iodine induced Riv. Ital. Igiene 47:104,1981. thyrotoxicosis. 84. Sava L, Ferrigno R., La Rocca C Padova G., Bonar- J. Clin. Endocrinol. Metab. 45: 25,1977. rigo G., Frascona L, Vigneri R. 99. Lopes de Oliveira A., Concalves M.J., Sobrinho L.G. Studio dell'endemia gozzigena nel distretto di Nicosia Endemic goiter in the island of S. Miguel (the Azores). (Sicilia Orientale). Acta Endocrinol. (Kbh.) 7 77: 200,1986. Minerva Endoer. 7: 263,1982. 100. Milcu St-M. 85. Squatrito S., Delange F., Trimarchi F., Lisis E., Vigneri R. Gusa Endemica. Distrofia endemicatireopata. Editu- Endemic cretinism in Sicily. ra Academiei Republicii Populäre Romine 1,1-1957, J. Endocrinol. Invest. 4: 295,1981. 1,1957. 86. The Italian Iodine Manifesto 101. Islambekov R.K., Nasarova L.M., Babatschanov D. Communication by Dr. A. Pinchera, 1986. Endemic goiter in the Choreskic distric of the USSR. 87. Vigneri R., Squatrito R., Polley R., Polosa P., Ermans Taschkent: USSR, Medical Pub., 1973, p. 1. A.M., Ingbar S.H. 102. Escobar del Rey F. Iodine Prophylaxis in an endemic area in Sicily: a new Goiter and iodine deficiency in Spain. method for iodine supplementation. Lancet 7 7:149,1985; cfr. IDD Newsletter 3: (4), 10, In: Reinwein D., Klein E. (Eds.) Diminished thyroid 1987. hormone formation. 103. Geiser J., Bürgi H., Grob P.J., Studer H. Schattauer, Stuttgart, 1982, p. 187. Bedeutung der Schilddrüsenkrankheiten in einer al• 88. Fenzi G.F., Ceccarelli C, Macchia E. lgemeininternistischen Klinik. Reciprocal changes of serum thyroglobulin and TSH Schweiz. Med. Wochenschr. 708:1152,1978. in residents of moderate endemic goiter area. 104. Schmid M., Schulthess C, Bürgi H., Studer H. Clin. Endocrinol (Oxf.) 23:115,1985. Jodmangel ist in der Schweiz noch immer ende• 89. Report No. 78 Ministry of Health - Amsterdam, The misch. Netherlands, 1981. Schweiz. Med. Wochenschr. 7 70:1290,1980.

218 Goiter and iodine deficiency in Europe

105. Steck A., Steck B., Köning M.P., Studer H. 117. Bachtarzi H.M., Benmiloud. Auswirkungen einer verbesserten Jodprophylaxe auf TSH-regulation and goitrogenesis in severe iodine Kropfendemie und Jodstoffwechsel. deficiency. Schweiz. Med. Wochenschr. 102: 829,1972. Acta Endocrinol. (Kbh.) 103: 21,1983. 106. Spinnler K., Studer K. 118. Grubeck-Loebenstein B., Kletter K., Kiss A., Vier- Die Jodversorgung in der Schweiz. 2. Schweize• happer H., Waldhäusl W. rischer Ernährungsbericht. Endemische Struma in Osterreich: Ist Jodmangel die Stuttgart Bern - Hans Huber Wien, 299,1984. primäre Kropfursache? Schweiz. Med. Wochenschr. 112:1526,1982. 107. Mordasini C, Abetel G., Lauterburg H., Ludi P., Perre- nound J.P., Schmid H, Suder H. 119. Sanchez-Franco F., Cacicedo L, Morreale de Es• Untersuchungen zum Kochsalzkonsum und Jodver• cobar G., Escobar del Rey F. sorgung der schweizerischen Bevölkerung. Nutrition and iodine versus genetic factors in endem• Schweiz. Med. Wochenschr. 114:1924,1984. ic goiter. J. Endocrinol. Invest. 6:185,1983. 108. Eser S.R. Le goiter endemique en Turquie et son Ätiologie. 120. Adams D.D., Kennedy T.H., Stewart J.C., Utiger R.E., Rev. med. Moy. Orient 23: 262,1966. Vidor F.f. Hyperthyroidism in Tasmania following iodine sup• 109. KologluS., Kologlu LB. plementation: Measurements of thyroid-stimulating Etiopathogenesis of endemic goiter. autoantibodies and thyrotropin. Istanbul medical Convention Symposium on thyroid J. Clin. Endocrinol. Metab. 41: 221 1975. diseases. Istanbul University Med. School, 1977, p. 35. 121. Belfiore A., Sava L, Runello F., Tomaselli L, Vigneri R. Solitary autonomously functioning thyroid nodules 110. Kologlu S., Kologlu LB., Kologlu M. and iodine deficiency. Effects of 10 year iodine Prophylaxis on thyroid biol- J. Clin. Endocrinol. Metab. 56: 283,1983. ogy and the place of TT3, TT4, FT3, FT4 and TSH in the diagnosis of various thyroid diseases in Turkey - a 122. Boukis M.A., Koutras D.A., Souvatzoglou A., Evange- comparative investigation. lopoulu A., Vrontakis M., Moulopoulos S.D. Proceedings of IV Balkan Congress of Endocrinol- Thyroid hormone and immunological studies in en• ogy, Printing Office of Ankara University, 1986, p. 269. demic goiter. J. Clin. Endocrinol. Metab. 57: 859,1983. 111. Urganciologlu I., Hatemi H., Kokoglu E., Fuven Y., Sur N., YilmazO. 123. Bürgi H., Baumgartner H., Steiger G. Iodine determination in drinking water samples of Gibt es eine obese Verträglichkeitsgrenze der ali• Turkey, in relation to the endemic goiter problem. mentären Jodzufurhr? Istanbul, University of Istanbul, Cerrahpase Medical Schweiz. Med. Wochenschr. 112: 2,1982. Faculty. Publication No. 3,1982. 124. Emrich D., Karkavitsas N., Facorro U., Schürnbrand 112. Barker D.J.P., Phillips D.I.W. P., Schreivogel I., Schicha H., Dirks H. Current incidence of thyrotoxicosis and past preval• Influence of increasing iodine intake on thyroid fune• ence of goiter in 12 British towns. tion in euthyroid and hyperthyroid states. Lancet 2:, 567,1984. J. Clin. Endocrinol. Metab. 54:1236,1982. 113. Phillips D.I.W., Barker D.J.P., Winter P.D., Osmond C. 125. Hall R., KöbberlingJ. Mortality from thyrotoxicosis in England and Wales Thyroid disorders associated with iodine deficiency and its association with the previous prevalence of and excess. endemic goiter. Raven Press, Serono Symposia, 1985, p. 1. J. Epidemiol. Comm. Health 37: 305,1983. 126. Heberer G., Speisberg F., Günther B., Kiffner E., Pick- 114. Phillips D.I.W., Nelson M., Barker D.J.P., Morris JA, ardt CR., Scriba P.C. Wood T.J. Chirurgie der Hyperthyreose. Iodine in milk and the incidence of thyrotoxicosis in Langenbecks Arch. Chir., 347 698,1978. England. 127. Leisner B., Igl W„ Scriba P.C. Clin. Endocrinol. (Oxf) 38: 61,1988. Fortschritte in der Diagnostik der autonomen Schild• 115. Tunbridge W.M.G. drüsenadenome. The spectrum of thyroid disease in a Community: The Akt. Endokr. Stoffw 1: 91,1980. Wickham survey. 128. Pfannenstiel P., Horster F.A. Clin. Endocrinol 7: 481,1977. Jodmangel in der Bundesrepublik Deutschland. 116. Wenlock R.W., Buss D.H., Moxon R.E., Bunton N.G. Wirksamkeit (und Risiko) der Kropfprophylaxe durch Trace nutrients. 4. Iodine in British Food. jodiertes Speisesalz. Brit. J. Nutr. 47: 381,1982. Dtsch. Med. Wochenschr. 107: 867,1982.

219 R. Gutekunst and P.C. Scriba

129. Purves H.D. 137. Sanchez-Castillo C.P., Branch W.J., James W.P.T. The aetiology and Prophylaxis of endemic goiter and A test for the validity of the lithium-marker technique cretinism. The New Zealand Experience. for monitoring dietary sources of salt in man. N.Z. Med. ISO: 477, 1974. Clin. Sei. 72:87,1987. 130. Stewart J.C., Vidor G.l. 138. Sanchez-Castillo C.P.. Warrender S., Whitehead T.P., Thyrotoxicosis induced by iodine contamination of James W.P.T. food - a common unrecognised condition? An assessment of the sources of dietary salt in a Br. Med. J. 7:372,1976. British population. 131. Wächter W., Pickardt CR., Gutekunst R., Horn K., Clin. Sei. 72: 95,1987. Köning A., Kavishe F.P., Scriba P.C. 139. Scriba P.C. Use of ultrasonography for goiter assesment in IDD: Kropfprophylaxe mit jodiertem Speise-salz. Studies in Tanzania. Dtsch. Arztebl 78:1677,1981. In: Hetzel B S, Dunn J.T., Stanbury J.B. (Eds). The 140. Delange F., Beckers C, Höfer R., König M.P., Monaco prevention of control of iodine deficiency and dis• F., Varrone S. orders. Neonatal Screening for congenital hypothyroidism in Elsevier Science Publ. B, V, Amsterdam, 1987, p. 95. Europe. Report of the Newborn Committee of the 132. Williams J., Ankrett V.O., Lazarus J.H., Volpe R. European Thyroid Association. Acta Endocrinol. Aetiology of hyperthyroidism in Canada and Wales. (Kbh) (Suppl. 233), 90:1979. J. Epidemiol. Commun. Health 37: 245,1983. 141. Jonckheer M., Coomans D., Broeckart I., van Paepe- 133. Habermann J., Jungermann A., Scriba P.C. gem R., Deconinck F. Qualität und Stabilität von jodierten Speisesalzen. Seasonal Variation of stable intra-thyroidal iodine in Ernährungs-Umschau 25: 45,1978. nontoxic goiter disclosed by X-ray fluorescence. J. Endocrinol. Invest 5: 27,1982. 134. Hetzel B.S. 142. van Thiel D., Wächter W., Triebel E., Habermann J., An overview of the prevention and control of iodine Marschner I., Scriba P.C. deficiency disorders. Assessmen of the eff icaey of iodine supplementation In: Hetzel B.S., Dunn J.T., Stanbury J.B. (Eds.), The by TSH determination in Tanzania. Prevention and Control of Iodine Deficiency Dis• Acta Endocrinol. (Suppl. 240) 96 (Kbh.), 9,1981. orders. Elsevier, Amsterdam, 1987, p. 7. 143. Pfannenstiel P. Direct and indirect costs caused by continuous io• 135. James W.P.T., Ralph A., C.P. Sanchez-Castillo. dine deficiency. The dominance of salt in manufactured food in the In: Hall R., Köbberling J. (Eds.), Thyroid disorders sodium intake of affluent societies. associated with iodine deficiency and excess. Lancet 7: 426,1987. Raven Press, Serono Symposia, 1985, p. 447. 136. Sanchez-Castillo C.P., Seidell J., James W.P.T. 144. Pfannenstiel P. The potential use of lithium as a marker for the as- Costs and benefits for the Community of iodine Pro• sessment of the sources of dietary salt: cooking stud• phylaxis. ies and physiological experiments in men. 17th Annual Meeting of the European Thyroid Asso• Clin. Sei. 72:81,1987. ciation, 1988.

220