The village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, the village was well-known area of severe iodine deficiency disorders (IDD). In 1952', distinguished Croatian endocrinologist Professor Josip Matovinovic carried out detailed village survey. Goiter prevalence in school-age children was 85.0% (with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg of salt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in all endangered areas of the country and no new cretins appeared. However, at the beginning of 1990' mild to moderate iodine deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school-age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 microg/dL. In 1996, the new obligatory regulation with 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after the new law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performed in 7-11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol in boys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in 2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26 girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the village of Rude demonstrated rising values in microg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in 2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999-2005 in boys and girls from the village of Rude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring of IDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians of UIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within the normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren

Dabelić, Nina

Jukić, Tomislav

Kusić, Zvonko

Ljubičić, Mate

Lukinac, Ljerka

Nöthig-Hus, Dunja

Rogan, Sunčica Andreja

English

The village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, the
village was well-known area of severe iodine deficiency disorders (IDD). In 1952’, distinguished Croatian endocrinologist
Professor Josip Matovinovi} carried out detailed village survey. Goiter prevalence in school-age children was 85.0%
(with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg of
salt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in all
endangered areas of the country and no new cretins appeared. However, at the beginning of 1990’ mild to moderate iodine
deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school-
-age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 mg/dL. In 1996, the new obligatory regulation
with 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after the
new law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performed
in 7–11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol in
boys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in
2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26
girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the village
of Rude demonstrated rising values in mg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in
2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999–2005 in boys and girls from the village of
Rude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in iodine-
sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring of
IDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians of
UIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within the
normal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren

Tomislav Jukić

Nina Dabelić

Sunčica Andreja Rogan

Dunja Nõthig-Hus

Ljerka Lukinac

Mate Ljubičić

Zvonko Kusić

Hrčak - Portal of scientific journals of Croatia

Coll. Antropol. 32 (2008) 4: 1251–1254Original scientific paperThe Story of The Croatian Village of Rudeafter Fifty Years of Compulsory Salt Iodinationin CroatiaTomislav Juki}1, Nina Dabeli}1, Sun~ica Andreja Rogan1, Dunja Nõthig-Hus1,Ljerka Lukinac1, Mate Ljubi~i}2 and Zvonko Kusi}11 Department of Oncology and Nuclear Medicine, University Hospital »Sestre milosrdnice«, Zagreb, Croatia2 Croatian National Institute of Public Health, Zagreb, CroatiaA B S T R A C TThe village of Rude is situated near Zagreb, the capital of Croatia in the last Alpine valley on Balkan. In the past, thevillage was well-known area of severe iodine deficiency disorders (IDD). In 1952’, distinguished Croatian endocrinolo-gist Professor Josip Matovinovi} carried out detailed village survey. Goiter prevalence in school-age children was 85.0%(with 2.3% of cretins in the village). In 1953, the first regulation on compulsory salt iodination with 10 mg of KI/kg ofsalt was established in former Yugoslavia. Ten years later a dramatic decrease in goiter prevalence was recorded in allendangered areas of the country and no new cretins appeared. However, at the beginning of 1990’ mild to moderate io-dine deficiency still persisted in Croatia. In 1991, the village of Rude survey demonstrated goiter prevalence in school--age children of 35.0% and median of urinary iodine excretion (UIE) of 7.4 mg/dL. In 1996, the new obligatory regulationwith 25 mg of KI/kg of salt was established in Croatia. The study aim was to monitor IDD status in the village after thenew law on compulsory salt iodination. Measurements of UIE and thyroid volumes (Tvol) by ultrasound were performedin 7–11-y-old schoolchildren living in the village of Rude. Medians of UIE and body surface area (BSA)-adjusted Tvol inboys and girls were calculated. The study included 84 children in 1997, 132 in 2000, 72 in 2002, 85 in 2003 and 46 in2004 for UIE measurement. Thyroid volumes were measured in 1999 (43 boys and 26 girls) and in 2005 (22 boys and 26girls). Data were compared with the new WHO/ICCIDD reference values. Medians of UIE in schoolchildren from the vil-lage of Rude demonstrated rising values in mg/dL: 11.4 in 1997, 14.3 in 2000, 17.3 in 2002, 15.4 in 2003 and 19.0 in2004. Significant decrease in BSA-adjusted Tvol was recorded from 1999–2005 in boys and girls from the village ofRude and in 2005 Tvol were within the normal range according to the new international reference values for Tvol in io-dine-sufficient schoolchildren. As a result of increased iodine prophylaxis, IDD no longer exist in Croatia. Monitoring ofIDD status in the village of Rude after new law on compulsory salt iodination in Croatia demonstrated rising medians ofUIE together with significant reduction of Tvol. In 2005, Tvol in schoolchildren from the village of Rude were within thenormal range according to the new international reference values for Tvol in iodine-sufficient schoolchildren.Key words: iodine deficiency, goiter, salt iodination, urinary iodine excretion, thyroid volume, schoolchildren, thevillage of RudeIntroductionThe village of Rude is situated about 25 km southwestof Zagreb, the capital of Croatia (Figure 1), in the valleyof the river Rudarska Gradna, the last Alpine valley onBalkan, bordered with mountains Ple{ivica, ^rnec andO{trc. The village of Rude probably dates back from earlymiddle-ages, but some data indicate that copper mineshad already existed in this area since antic ages. The vil-lage was named after the mines that were exploited inthis area; »Rude« in Croatian language means ores inEnglish. The valley was settled with German minersfrom Saksonia in XVI century by Croatian noble familyZrinski1 and foreign owners of the mines. German min-ers remained in this area, marrying with Croatian girls.The community kept some old habits but their nativeGerman language was forgotten. Besides the mining, theagriculture was the main activity of the inhabitants.1251Received for publication December 15, 2007In the past, the village was well-known area of severeiodine deficiency, and therefore the object of many epide-miological investigations. Endemic goiter was the mostcommon disease of the village population. In 1952, dis-tinguished Croatian endocrinologist Professor Josip Ma-tovinovi} carried out detailed village survey2. The goiterwas detected in 83% of 865 individuals with increasingprevalence with age. Goiter prevalence in schoolchildrenand adolescents was 85.0%. It was the place with thehighest prevalence of goiter in Croatia before the intro-duction of compulsory salt iodination in former Yugosla-via in 1953. Professor Matovinovi}3 gave detailed de-scription of the life in the village at the beginning of the1950’s: »The houses were small and over-crowded, withan average of five family members per household. The es-sential dietary products were corn bred, potatoes andbeans, with little meat or milk. Wine was an importantsource of calories – 7.4% drank more than one liter perday, and 83% of children consumed alcohol«. A young girl»without a neck« wasn’t considered beautiful and evenangels in the local church were also represented with goi-ter (Figure 2). Drinking water from wells and smallbrooks contained an average of 1.3 and 0.43 mg iodine perliter respectively. The most tragic complication of iodinedeficiency in the village was endemic cretinism. Therewere 20 cretins in the village (2.3% of the village popula-tion). The majority was severely mentally retarded. Pro-fessor Matovinovi} described cretins as good, poor fel-lows who depended inseparably to the life of his mother.After her death they were condemned to isolation anddeath, as it was described in the sentence: »Her care forher unfortunate child reflected boundless love, terror ofhis disease, the height of ignorance and superstition, tor-ment of guilt, and desolation of hopelessness. She wasavare that after her death her beloved cretin would mostlikely suffer from neglect, malnutrition, or die in confine-ment«3.Salt Iodination in Former YugoslaviaIn 1953 the first regulation on obligatory salt iodin-ation for both human and animal consumption, requir-ing 10 mg of KI per kg of salt was established in formerYugoslavia.Ten years later a dramatic decrease in goiter preva-lence was recorded in all endangered areas of the countryand no new cretins appeared4. In endemic areas thestructure of growth normalized and there was an in-crease of intellectual abilities and success in school amongchildren. However, the goiter was still found in 20–30%of children.The Village of Rude Survey in 1991–1993At the beginning of the 1990’s The National Commit-tee for Eradication of Goiter and Control of Iodine Pro-phylaxis was founded. The Committee initiated a com-prehensive epidemiological research with the aim of de-termining the state of iodine intake in different parts ofCroatia5,6. A part of the nationwide survey was carriedout in the village of Rude6. A total of 200 schoolchildrenwere included in the village survey (110 boys and 90girls). The prevalence of goiter among schoolchildrenwas determined by palpation of the neck according to thePAHO/WHO classification7. Urinary iodine excretion wasmeasured by the instructions of ICCIDD/WHO and mod-ified colometric method based on the Sandell-Kalthoffreaction8. The results of the investigation demonstratedthat iodine deficiency in the village still persisted. Goiterwas detected in 26% of schoolchildren aged 7–11 years(n=88) and in 43% of schoolchildren aged 12–15 years(n=112). The urinary iodine excretion in those children(n=118) varied between 0.5–19 mg/dL with a median of7.4 mg/dL. Only few were distinctly low and 30% were be-low 5 mg/dL, while 80% were below 10 mg/dL. The overallprevalence of goiter in the village was 35%6.T. Juki} et al.: The Story of the Croatian Village of Rude, Coll. Antropol. 32 (2008) 4: 1251–12541252RUDEZAGREBFig. 1. Geographic location of the village of Rude.Fig. 2. Angel with goiter in the local church near the village ofRude, where 85% of the children had goiter in 1950’.The New Regulation and SuccessfulElimination of Iodine DeficiencyDisorders in CroatiaIn 1996, the new obligatory regulation requiring 25mg of KI/kg of salt was established in Croatia9,10. In 2002,thyroid volumes and medians of urinary iodine excretionfrom all four major Croatian regions were for the firsttime within the normal range according to the WHO/ICCIDD reference values. An overall median of urinaryiodine excretion for all four major geographic regions ofCroatia was 14.0 mg/dL11–14. Both domestic and importedsalt corresponded with the effective regulation on iodin-ation.The Village of Rude Surveys afterthe New Obligatory RegulationThe study aim was to monitor IDD status in the vil-lage after the implementation of the new law on compul-sory salt iodination in Croatia.Measurement of UIE and thyroid volume by ultra-sound was performed in 7–11-y-old schoolchildren livingin the village of Rude. The prevalence of goiter in school-children was assessed by neck ultrasound using 7,5 MHzlinear transducer (Tossbee, Toshiba, Japan). Urinaryioine excretion was measured by the instructions ofICCIDD/WHO and modified colometric method8. Me-dians of UIE and body surface area – adjusted thyroidvolumes in boys and girls were calculated. The study in-cluded 84 children in 1997, 132 in 2000, 72 in 2002, 85 in2003 and 46 in 2004 for UIE measurement. Thyroid vol-umes were measured by ultrasound in 1999 (43 boys and26 girls) and in 2005 (22 boys and 26 girls). Data werecompared with the new international reference valuesfor thyroid volume in iodine-sufficient schoolchildren15.Medians of urinary iodine excretion in schoolchildrenfrom the village of Rude demonstrated rising values:from 7.4 mg/dL in 1991, and after the new regulation 11.4mg/dL in 1997, 14.3 mg/dL in 2000, 17.3 mg/dL in 2002,15.4 mg/dL in 2003, and 19.0 mg/dL in 2004 (Table 1). Sig-nificant decrease in BSA-adjusted thyroid volumes wasrecorded from 1999 to 2005 in boys (Figure 3) and girls(Figure 4) from the village of Rude. In 2005, Tvol inschoolchildren from the village of Rude were within thenormal range according to the new international refer-ence values for Tvol in iodine-sufficient schoolchildren.DiscussionAs a result of increased iodine prophylaxis, IDD nolonger exist in Croatia. Nowadays, Croatia is interna-tionally recognized as iodine sufficient country16. Moni-toring of the IDD status in the village of Rude after newlaw on compulsory salt iodination in Croatia demon-strated rising medians of urinary iodine excretion inschoolchildren together with significant reduction of thy-T. Juki} et al.: The Story of the Croatian Village of Rude, Coll. Antropol. 32 (2008) 4: 1251–12541253Thyroidvolume(mL)98765432100.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6BSA (m )2M Rude 1999M Rude 2005M P50M P97Fig. 3. Thyroid volumes in boys from the village of Rude in 1999(M Rude 1999) and 2005 (M Rude 2005) adjusted for body sur-face area (BSA) together with 50th percentile (M P50) and 97thpercentile (M P97) of new international reference values.Thyroidvolume(mL)98765432100.8 0.9 1.0 1.1 1.2 1.3 1.4 1.5 1.6BSA (m )2F Rude 1999F Rude 2005F P50F P97Fig. 4. Thyroid volumes in girls from the village of Rude in 1999(F Rude 1999) and 2005 (F Rude 2005) adjusted for body surfacearea (BSA) together with 50th percentile (F P50) and 97th per-centile (F P97) of new international reference values.TABLE 1URINARY IODINE EXCRETION IN SCHOOLCHILDRENFROM THE VILLAGE OF RUDEYearof surveyNumber ofchildrenMedian(g/dL)< 5 g/dL(in %)< 10 g/dL(in %)1997 84 11.4 10.7 41.72000 132 14.3 5.6 26.42002 72 17.3 8.3 26.42003 85 15.4 14.1 25.92004 46 19.0 6.5 23.9roid volume in both boys and girls. Thyroid volumes inschoolchildren from the village of Rude adjusted for BSAwere in 2005 within the normal range according to thenew international reference values for thyroid volume iniodine-sufficient schoolchildren. The struggle against io-dine deficiency disorders in Croatia will contribute to thebenefit of future generationsAcknowledgementsThe research on goiter and iodine deficiency in the vil-lage of Rude was funded by the Ministry of Science, Edu-cation and Sport of the Republic of Croatia under grant134-1342428-2430 for the project »Carcinogenesis inThyroid and Goiter in Croatia«.R E F E R E N C E S1. GU[I] B, Do Anthropogeographic factors take a strumigenic ef-fect. In: FERBER, M, KOVA^EVI] M. (Eds) Drugi Jugoslavenski Sim-pozij o Endemskoj Gu{avosti (KOMNIS, Zagreb, 1961). — 2. FERBER E,MATOVINOVI] J, KOVA^I] N, R. BUZINA R, Higijena, 7 (1956) 295. —3. MATOVINOVI] J, Ann Rev Nutr, 3 (1983) 341. — 4. BUZINA R, Am JClin Nutr, 23 (1970) 1085. — 5. KUSI] Z, \AKOVI] N, KAI]-RAK A,KARNER I, LECHPAMMER S, MESARO[-[IMUN^I] E, PETROVI] I,RON^EVI] S, SMOJE J, STANI^I] A, VALENT I, DELANGE F, JEndocrinol Invest, 19 (1996) 210. — 6. KUSI] Z, LECHPAMMER S, CollAntropol, 21 (1997) 499. — 7. DELANGE F, BASTANI S, BENMILOUDM, Definitions of endemic goiter and cretinism, classification of goiter sizeand severity of endemias, and survey techniques. In: DUNN JT, PRE-TELL E, DAZA CH, VITERI FE (Eds) Towards the eradication of ende-mic goiter, cretinism and iodine deficiency (Pan American Health Organi-zation, PAHO/WHO Scientific Publication No. 502., Washington, 1986).— 8. WAWSCHINEKO, EBER O, PETEKW,WAKONIG P, GÜRAKAR A,ÖGKC, 8 (1985) 13. — 9. KUSI] Z, Lijec Vjesn, 118 (1996) 306. — 10.KUSI] Z, LECHPAMMER S, DELANGE F, J Endocrinol Invest, 20 (1997)346. — 11. KUSI] Z, NOVOSEL SA, DABELI] N, PUNDA M, RON-^EVI] S, LABAR @, LUKINAC LJ, NOTHIG-HUS D, LECHPAMMER S,STANI^I] A, KAI]-RAK A, MESARO[-KANJSKI E, KARNER I,SMOJE J, MILANOVI] N, KATALENI] M, JURE[A V, SARNAVKA V, JEndocrinol Invest, 26 (2003) 738. — 12. KUSI] Z, IDD Newsletter, 5(2003) 27. — 13. KUSI] Z, JUKI] T, Coll Antropol, 29 (2005) 9. — 14.KUSI] Z, JUKI] T, DABELI] N, ROGAN SA, RON^EVI] S, LUKINACLJ, NOTHIG-HUS D, KARNER I, STANI^I] A, PUNDA M, SMOJE J,Thyroid, 15 (Suppl 1) (2005) 174. — 15. ZIMMERMAN MB, HESS SY,MOLINARI L, DE BENOIST B, DELANGE F, BRAVERMANN LE,FUJIEDA K, YOSHIYA I, JOOSTE PL, MOOSA K, PEARCE EN,PRETELL EA, SHISHIBA Y, Am J Clin Nutr, 79 (2004) 231. — 16. VITTIP, DELANGE F, PINCHERA A, ZIMMERMANN M, DUNN JT, Lancet,361 (2003) 1226.T. Juki}Department of Oncology and Nuclear medicine, University Hospital »Sestre milosrdnice«, 29 Vinogradska Street,10000 Zagreb, Croatiae-mail: tjukic@kbsm.hrPRI^A O SELU RUDE PEDESET GODINA NAKON UVO\ENJA OBVEZNE JODNEPROFILAKSE U HRVATSKOJS A @ E T A KSelo Rude smje{teno je nadomak Zagreba u posljednjoj Alpskoj dolini na Balkanu. To je podru~je u pro{losti bilopoznato po te{kom nedostatku joda. Eminentni hrvatski endokrinolog svjetskog ugleda, profesor Josip Matovinovi}proveo je 1952 u Rudama opse`no epidemiolo{ko istra`ivanje i utvrdio prevalencija gu{avosti u {kolske djece od 85,0%(uz 2,3% kretena u seoskoj populaciji). Godine 1953 prvi zakon o obveznoj jodiranju soli sa 10 mg KI/kg soli uveden je ubiv{oj Jugoslaviji. Deset godina kasnije zabilje`eno je dramati~no smanjenje prevalencije gu{avosti u svim zahva}enimpodru~jima Hrvatske uz nestanak kretenizma. Me|utim, po~etkom 1990-tih blagi do umjereni nedostatak joda jo{ uvijekje postojao u Hrvatskoj. Godine 1991, epidemiolo{ko istra`ivanje stanja gu{avosti u selu Rude pokazalo je prevalencijugu{avosti u {kolske djece 35,0% uz medijan izlu~ivanja joda urinom 7,4 mg/dL. Godine 1996 uveden je u Hrvatskoj novizakon o obveznom jodiranju soli s 25 mg KI/kg soli. Cilj ovoga istra`ivanja je pra}enje stanja gu{avosti i unosa joda uselu Rude nakon uvo|enja novog zakona o obveznom jodiranju soli. Provedeno je vi{estruko mjerenje izlu~ivanja jodaurinom i ultrazvu~no mjerenje volumena {titnja~e u {kolske djece u dobi od 7 do 11 godina. Dobivene podaci su prika-zani kao medijani izlu~ivanja joda urinom te volumeni {titnja~e u dje~aka i djevoj~ica uskla|eni prema povr{ini tijela. Uistra`ivanje izlu~ivanja joda urinom uklju~eno je 84 {kolske djece u 1997 godini, 132 u 2000, 72 u 2002, 85 u 2003 i 46{kolske djece u 2004 godini. Ultrazvu~no mjerenje volumena {titnja~e provedeno je 1999 godine (43 dje~aka i 26 djevoj-~ica) i 2005 godine (22 dje~aka i 26 djevoj~ica). Podaci su uspore|eni s novim referentnim vrijednostima WHO/ICCIDD.Medijani izlu~ivanja joda urinom u {kolske djece u selu Rude porasli su nakon novog zakona (mg/dL): 11,4 u 1997, 14,3 u2000, 17,3 u 2002, 15,4 u 2003 i 19,0 u 2004 godini. Zna~ajno smanjenje volumena {titnja~e uskla|enih prema povr{initijela utvr|eno je u dje~aka i djevoj~ica iz sela Rude, a u 2005 godini te vrijednosti bile su granicama normale u odnosuna nove referentne vrijednosti WHO/ICCIDD. Kao rezultat uvo|enja novog zakona o obveznom jodiranju soli 1996godine danas je iskorijenjena gu{avost u {kolske djece u Hrvatskoj i op}enito svi poreme}aji uzrokovani nedostatkomjoda.T. Juki} et al.: The Story of the Croatian Village of Rude, Coll. Antropol. 32 (2008) 4: 1251–12541254

The Story of The Croatian Village of Rude after Fifty Years of Compulsory Salt Iodination in Croatia

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The story of the Croatian village of Rude after fifty years of compulsory salt iodination in Croatia

The story of the Croatian village of Rude after fifty years of compulsory salt iodination in Croatia

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