Iodine Status Assessment in Campania (Italy) As Determined by Urinary Iodine Excretion

Home , Campania, Caserta

Nutrition 25 (2009) 926–929 www.nutritionjrnl.com Applied nutritional investigation Iodine status assessment in Campania (Italy) as determined by urinary iodine excretion

Claudia Mazzarella, Ph.D.a, Daniela Terracciano, Ph.D.a, Angelina Di Carlo, Ph.D.b, Paolo Emidio Macchia, M.D.c, Eduardo Consiglio, M.D.d, Vincenzo Macchia, M.D.a,*, and Angela Mariano, Ph.D.a

aDipartimento di Biologia e Patologia Cellulare e Molecolare ‘‘L. Califano’’, Universita`degli Studi di Napoli Federico II, Naples, Italy bDipartimento di Medicina Sperimentale, Universita`di Roma ‘‘La Sapienza’’, Rome, Italy cDipartimento di Endocrinologia ed Oncologia Molecolare e Clinica, Facolta`di Medicina e Chirurgia, Universita`degli Studi di Napoli Federico II, Naples, Italy dIstituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore, Naples, Italy Manuscript received September 23, 2008; accepted January 31, 2009

Abstract Objective: Mild iodine deficiency was first documented in Campania in the 1990s. We assessed the urinary iodine nutritional status of schoolchildren in Campania before the introduction of legislation for salt iodization and compared the findings with previous results to evaluate to what extent ‘‘silent’’ iodine prophylaxis, which accompanies socioeconomic advances, affects iodine status. Methods: We examined 10552 schoolchildren aged 9–13 y from the five Campania provinces. The study was conducted from April 1999 to October 2002. Urinary iodine excretion was measured in morning urine samples with the AutoAnalyzer 3, an automated system based on the Sandell-Kolthoff reaction. Data were interpreted according to World Health Organization criteria. Results: The median urinary iodine excretion level in Campania was less than 100 mmg/L, which indicates insufficient iodine intake. Mild iodine deficiency was identified in all provinces, namely Napoli, Salerno, Caserta, Avellino, and Benevento, with median urinary iodine excretions of 87, 81, 72, 64, and 61 mg/L, respectively. Overall, the analysis of frequency distribution showed values below 50 and 100 mg/L in 32% and 61% of children, respectively. These values were lower than those previously reported for Campania. Conclusion: This study confirms that Campania is a mild iodine deficiency area. The decrease in iodine deficiency versus previous studies indicates that silent prophylaxis plays a relevant role in this condition, but it is not sufficient to eradicate it. Our data will serve as a basis for future evaluations of iodine status in Campania. Ó 2009 Elsevier Inc. All rights reserved.

Keywords: Urinary iodine excretion; Iodine intake; Iodine deﬁciency; Goiter; Iodine prophylaxis

Introduction diet is associated with a wide spectrum of disorders, collec- tively known as iodine deficiency disorders (IDDs) [3]. Iodine is the main substrate for thyroid hormone biosyn- Accordingly to the World Health Organization (WHO) thesis and is thus essential for thyroid function [1,2].An [4,5], an optimal iodine intake is 150–300 mg/d, which corre- adequate iodine intake is necessary for normal growth, devel- sponds to a median urinary iodine excretion (UIE) of 100– opment, and functioning of the brain and body. Iodine can be 200 mg/L. A median UIE from 50 to 100 mg/L indicates assumed only through the diet [1], and an iodine-deficient mild iodine deficiency, values from 20 to 50 mg/L indicate moderate iodine deficiency, and values below 20 mg/L indicate severe iodine deficiency. This work was supported by the Programma per l’eradicazione del Gozzo Mild iodine deficiency causes slight changes in thyroid Endemico nell’Italia Meridionale of the Italian National Research Council (1999). gland morphology without altering thyroid function; this *Corresponding author. Tel.: þ39-81-746-3616; fax: þ39-81-746-3676. condition is classified as endemic euthyroid goiter. Subjects E-mail address: [email protected] (V. Macchia). living in areas of moderate iodine deficiency are at risk of

0899-9007/09/$ – see front matter Ó 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.nut.2009.01.020 C. Mazzarella et al. / Nutrition 25 (2009) 926–929 927 hypothyroidism and mental retardation. Severe iodine defi- replaced by ultraviolet irradiation [17]. Calibration of the ciency can result in hypothyroidism and goiter associated analyzer was performed according to the manufacturer’s in- with such relevant clinical manifestations as endemic cretin- structions, using standard potassium iodide solutions in ism. Consequently, the socioeconomic consequences of low, medium, and high concentrations of iodine, in triplicate IDDs are potentially very serious [5,6]. in each assay. Standards and reference ranges are appropriate At present, iodine deficiency is a public health problem in for children [7]. According to the statistician’s suggestions, 54 countries worldwide. In particular, nearly 60% of school- 676 samples below the analytical sensitivity of the method age children in Europe have an insufficient intake of iodine (5 mg/L) were excluded from the analysis, as were 369 sam- [7]. According to the WHO, measurement of UIE is the ples with a UIE above 350 mg/L because such high values most accurate method with which to assess a population’s io- have been attributed to extradietary iodine intake [8]. dine status [4,5] In fact, 90% of iodine intake is excreted in The results are reported as medians rather than means, urine. Various groups have investigated iodine nutritional because urinary iodide levels of schoolchildren are not nor- status by monitoring UIE in areas of Italy other than Campa- mally distributed [5]. We used the Wilcoxon-Mann-Whitney nia [8–10]. Previous studies of UIE in children and adults test for comparisons. P < 0.05 was considered statistically have shown that, based on WHO criteria, Campania is an significant. area with mild to moderate iodine deficiency [11–13]. Median UIE values and interquartile ranges (IQRs) of the The consequences of iodine deficiency and of IDDs can be 8874 samples collected in the five provinces of Campania are prevented by ensuring an optimal iodine intake [7]. Various shown in Fig. 1. Overall, the median UIE was 79 mg/L (IQR strategies have been devised to achieve this aim, one of the 39–140), with no significant difference between male and fe- most effective being food fortification with iodized salt. In male subjects (data not shown). addition, it appears that the ‘‘silent’’ prophylaxis, namely the increased consumption of iodine-rich products associated with socioeconomic development, plays a significant role in Results IDD prevention [10,14,15]. Despite such encouraging results, silent iodine prophylaxis alone may not be sufficient The median UIE value was always below 100 mg/L, to eradicate completely iodine deficiency. although it varied among provinces: Benevento and Avellino We report UIE levels in Campania schoolchildren and had the lowest median UIE values (61 mg/L, IQR 29–114, analyzed the effects of silent prophylaxis by comparing our and 64 mg/L, IQR 32–113, respectively) and Napoli results with previous studies. In addition, we have established (87 mg/L, IQR 46–151) and Salerno (81 mg/L, IQR 41– a UIE setpoint that can be used to evaluate the effects of 152) the highest. Schoolchildren in the province of Caserta mandatory salt fortification in the Campania population in had a median UIE value of 72 mg/L (IQR 36–129). The Wil- the future. coxon-Mann-Whitney rank sum test revealed statically significant differences in the median UIE when Avellino, Benevento, and Caserta provinces were compared with the Materials and methods provinces of Napoli and Salerno. According to the Italian National Institute of Statistics We selected a population of school-age children for this [18], Campania is divided into four geographic zones that dif- study because of ready access to schools, and because this fer in altitude and distance from the coast (inland mountains, populations reflects current rather than remote iodine nutri- inland hills, coastal hills, and lowlands). The median UIE and tional status in the community [7]. The study population IQR calculated for each zone are listed in Table 1. The UIE was constituted by 10 552 schoolchildren from the five differed significantly among various geographic zones. Campania provinces (Napoli, Salerno, Caserta, Avellino, We next clustered UIE in four classes: 5–19, 20–49, and Benevento): 5487 boys and 5065 girls 9 to 13 y of age. 50–99, and 100–350 mg/L (Fig. 2). As expected, the high- The population was selected according to well-established est percentages of samples with a UIE from 5 to 19 mg/L criteria as reported elsewhere [16]. Parents provided signed occurred in Avellino (14%) and Benevento (18%), and informed consent to the study. Avellino and Benevento are the lowest were in Napoli (9%) and Salerno (10%). More- mainly inland mountain/hill zones, whereas Caserta, Napoli, over, in the provinces of Avellino and Benevento, about and Salerno are mainly coastal, lowland zones. 40% of schoolchildren had UIE values below 50 mg/L, From April 1999 to October 2002, urine samples were col- whereas the highest percentage of samples from 100 to lected in the morning into screw-cap plastic tubes. All urine 350 mg/Loccurredinschoolchildrenintheprovincesof samples were taken to the laboratory, frozen, and stored at Napoli (44%) and Salerno (43%). The iodine deficiency 20 C until analysis. Urine iodine levels were analyzed status of schoolchildren in Caserta province was interme- with an automated system (Autoanalyzer 3 system, diate between those of Napoli and Salerno. Therefore, Bran þ Luebbe GmbH, Nordestedt, Germany), using the the highest degree of iodine deficiency in Campania oc- ceric-arsenious acid reaction and a modified digestion curred in Avellino and Benevento provinces, which corre- method in which the conventional acid digestion was spond to the areas with largest number of areas classified 928 C. Mazzarella et al. / Nutrition 25 (2009) 926–929

Fig. 1. Median and interquartile range of UIE in the five provinces of Campania. There were significant differences for the provinces of Avellino, Benevento, and Caserta versus the provinces of Napoli and Salerno (P < 0.0001). Only the median UIE between the provinces of Avellino and Benevento was not significantly different (P ¼ 0.8292). Comparisons were done with the Wilcoxon-Mann-Whitney rank sum test. Avellino and Benevento are mainly inland mountain/hill zones, whereas Caserta, Napoli, and Salerno are mainly coastal, lowland zones. UIE, urinary iodine excretion. as inland mountain or inland hill [18]. In addition, it Discussion should be noted that, when the number of samples excluded from median analysis was analyzed, the following Iodine deficiency is considered a public health problem in distribution of the lowest values in the five provinces was countries with a median UIE level below 100 mg/L [5].Inour found: total values in Campania 676 samples (7% of total), study, the median UIE level in Campania as a whole was Avellino 173 of 1519 (11%), Benevento 68 of 397 (17%), 72 mg/L. Moreover, the median UIE did not reach 100 mg/ Caserta 97 of 1566 (6%), Napoli 214 of 3765 (6%), and L in any of the five Campania provinces. Salerno 124 of 2303 (5%). These data clearly suggest Iodine intake in a given population can be estimated from that in the provinces with a lower median iodine excretion the proportion of the population with a low UIE [19]:according the percentage of data below the analytical sensitivity of to WHO criteria, in an iodine sufficient area, UIE should be be- the method is higher. low 50 mg/l in fewer than 20% and below 100 mg/l in fewer It has been suggested that, in a given population, iodine than 50% of the examined samples [5]. In the school-age pop- deficiency can be identified from a high prevalence of sam- ulation of Campania, UIEs were below 50 mg/L in 37% of sub- ples with UIE levels below a certain value [19]. As expected, jects and below 100 mg/L in 64% of subjects. Therefore, our the highest percentages of UIE below the sensitivity of the data demonstrate that, at the time of our investigation, Campa- method occurred in schoolchildren from the provinces of nia is an area of mild iodine deficiency, which is more pro- Avellino and Benevento (11.2% and 16%, respectively). In nounced in the provinces of Avellino and Benevento. the other provinces, the percentages of these values were The UIE levels observed in our study are higher than those 5.2% (Salerno), 5.4% (Napoli), and 5.9% (Caserta). previously reported for Campania [8,11–13]. In the absence In conclusion, our data indicate that schoolchildren from of specific iodine prophylaxis programs, the increase in all five Campania provinces have mild iodine deficiency, UIE may be the consequence of silent iodine prophylaxis. and the condition is more pronounced in children from It has been suggested that the decline of iodine deficiency Avellino and Benevento. in areas without specific iodine prophylaxis programs is the result of silent prophylaxis, which is associated with socioeconomic development and increased consumption of Table 1 iodine-rich products from localities distant from iodine- UIE in different geographic zones in Campania* deficient areas [10,14,15]. Geographic zone Samples Median UIE (mg/L) IQR Our study confirms that iodine deficiency is more prevalent in mountain areas than in lowlands, which is consistent with en- Inland mountains 798 60 32–114 Inland hills 1975 72 34–129 vironmental conditions such as the lack of iodine in soil and wa- Coastal hills 2522 90 47–153 ter of mountainous areas [20]. The comparison of our data with Lowlands 3288 81 41–143 previous reports demonstrates a more pronounced increase in IQR, interquartile range; UIE, urinary iodine excretion UIE levels in mountain areas, mostly in the province of Benev- * All comparisons were highly significant (P < 0.05) using the Wilcoxon- ento, which suggests that, in the previous decade, silent iodine Mann-Whitney rank sum test. prophylaxis has produced a stronger effect in this area. C. Mazzarella et al. / Nutrition 25 (2009) 926–929 929

even eradicate iodine deﬁciency; consequently, our data will be useful for comparison purposes in future studies.

References

[1] DeGroot LJ. Kinetic analysis of iodine metabolism. J Clin Endocrinol Metab 1966;26:149–73. [2] DeGroot LJ, Niepomniszcze H. Biosynthesis of thyroid hormone: basic and clinical aspects. Metabolism 1977;26:665–718. [3] Hetzel BS. Iodine deficiency disorders (IDD) and their eradication. Lancet 1983;2:1126–9. [4] Delange F, Burgi H, Chen ZP, Dunn JT. World status of monitoring iodine deficiency disorders control programs. Thyroid 2002; 12:915–24. [5] WHO, UNICEF, ICCIDD. Assessment of iodine deficiency disorders and monitoring their elimination: a guide for programme managers. 2nd ed. Geneva: World Health Organization; 2001. [6] de Benoist B, Andersson M, Egli I, Takkouche B, Allen H. Iodine status worldwide. Geneva: World Health Organization; 2004. [7] Andersson M, Takkouche B, Egli I, Allen HE, de Benoist B. Current global iodine status and progress over the last decade towards the elimination of iodine deficiency. Bull World Health Organ 2005;83:518–25. [8] Ando`S, Maggiolini M, Di Carlo A, Diodato A, Bloise A, De Luca GP, et al. Endemic goiter in Calabria: etiopathogenesis and thyroid function. J Endocrinol Invest 1994;17:329–33. [9] Aghini-Lombardi FAL, Martino E, Vitti P, Maccherini D, Leoli F, Rago T, et al. The spectrum of thyroid disorders in an iodine-deficient community: the Pescopagano survey. J Clin Endocrinol Metab 1999; 84:561–6. [10] Vermiglio F, Finocchiaro MD, Lo Presti VP, La Torre N, Nucifora M, Trimarchi F. Partial beneficial effects of the so called ‘‘silent iodine prophylaxis’’ on iodine deficiency disorders (IDD) in northeastern Sicily endemia. J Endocrinol Invest 1989;12:123–6. [11] Nasti A, Pisano G, Mariano A, Macchia V. Urinary iodine excretion in the Campania region. Ann Ist Super Sanita 1998;34:413–6. Fig. 2. Relative frequency distribution of urinary iodine excretion levels in [12] Pagliara S, Spagnuolo E, D’Avanzo A, Vitale M, Macchia PE, schoolchildren by district. Avellino and Benevento are mainly inland moun- Salvatore D, et al. Widespread endemic goiter and iodine deficiency tain/hill zones, whereas Caserta, Napoli, and Salerno are mainly coastal, low- in the province of Avellino. Ann Ist Super Sanita 1998;34:417–21. land zones. [13] Salerno M, Di Maio S, Pisaturo L, Mariano A, Macchia V. Fetal goiter in a iodine-deficient area. J Endocrinol Invest 1998;21:721–2. It has been reported that silent iodine prophylaxis is not [14] Delange F, Van Onderbergen A, Shabana W, Vandemeulebruoche E, sufficient to ensure an adequate iodine intake in a population, Vertongen F, Gnat D, et al. Silent iodine prophylaxis in Western Europe and active iodine prophylaxis is required also in industrial- only partly corrects iodine deficiency; the case of Belgium. Eur J Endo- crinol 2000;143:189–96. ized countries with a high intake of processed foods [14]. [15] Regalbuto C, Salamone S, La Rosa GL, Calaciura F, Buscema M, Universal salt iodization is the main strategy used to increase Vigneri R. [Iodine deficiency and iodine prophylaxis experience in Si- iodine intake and prevent the consequences of IDDs [5]. cily]. Ann Ist Super Sanita 1998;34:429–36. Until March 2005, the consumption of iodized salt in Italy [16] WHO/UNICEF/ICCIDD. Indicators for assessing iodine deficiency was limited to a minority of the population [21]. In March disorders and their control programmes. Report of a joint consultation, 3–5 November 1992, review version. Geneva: World Health 2005, a law requiring mandatory active iodine prophylaxis Organization; 1993. was approved. The UIE data reported in this study can serve [17] Tsuda K, Namba H, Nomura T, Yokoyama N, Yamashita S, Izumi M, as a basis to evaluate the effects of mandatory salt fortifica- et al. Automated measurement of urinary iodine with use of ultraviolet tion in Campania in the next decade. irradiation. Clin Chem 1995;41:581–5. [18] ISTAT Istituto Nazionale di Statistica Annuario Statistico Italiano. 2008; Rome, Italy. Conclusions [19] Bourdoux PDF, Filetti S, Thilly C, Ermans AM. Reliability of the iodine/creatinine ratio: a myth? In: Hall R, Knobberling J, editors. Our results confirm Campania as an area of mild iodine Thyroid disorders associated with iodine deficiency and excess. New deficiency. Although silent iodine prophylaxis has certainly York: Raven; 1985, vol. 22, p. 45–152. [20] Ortner DJ, Hotz G. Skeletal manifestations of hypothyroidism from played a role in decreasing iodine deficiency in Campania, Switzerland. Am J Phys Anthropol 2005;127:1–6. the condition still affects a large percentage of the population. [21] Aghini-Lombardi F, Antonangeli L. Iodine prophylaxis legislation in It is expected that mandatory salt iodization will decrease or Italy. Ann Ist Super Sanita 1998;34:363–6.