|Year : 2017 | Volume
| Issue : 1 | Page : 85-89
Improving iodine nutritional status and increasing prevalence of autoimmune thyroiditis in children
Srinivasan Palaniappan1, Lakshmi Shanmughavelu2, Hemchand K Prasad3, Sundari Subramaniam4, Nedunchezian Krishnamoorthy3, Lakshmi Lakkappa5
1 Department of Pediatric Intensive Care, Sri Ramachandra Medical College, Chennai, Tamil Nadu, India
2 Departent of Pediatrics, Stanley Medical College, Chennai, Tamil Nadu, India
3 Department of Pediatrics, Mehta Children's Hospital, Chennai, Tamil Nadu, India
4 Department of Pediatrics, Institute of Child Health and Hospital for Children, Chennai, Tamil Nadu, India
5 Department of Pediatrics, CSI Hospital, Bengaluru, Karnataka, India
|Date of Web Publication||19-Dec-2016|
Hemchand K Prasad
Mehta Children's Hospital, 2, MC Nichols Road, Chetpet, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Objective: The objective of this study is to evaluate the link between excess iodine intake as evidenced by increased urinary iodine excretion (UIE) and autoimmune thyroiditis in children and to assess the correlation between UIE and thyroid microsomal antibody (thyroid peroxidase [TPO]) titers in children. Materials and Methods: All children with goiter between age group 6 and 12 years, were subjected to blood tests for free thyroxine, thyroid stimulating hormone, and TPO antibody, fine needle aspiration was advised for all children with goiter. Forty-three children with confirmed autoimmune thyroiditis served as cases, and 43 children with euthyroid goiter with workup negative for autoimmune thyroiditis and iodine deficiency were enrolled as controls. UIE was estimated in spot urine sample for both cases and controls. The levels of urinary iodine were compared between cases and controls. Results: The levels of urinary iodine were significantly higher in children with autoimmune thyroiditis as compared with control. There was a positive correlation between UIE and antimicrosomal antibody titers among cases. Among cases 65% children had subclinical hypothyroidism, 27.9% had overt hypothyroidism and 7% of cases, and 100% of controls had euthyroid functional status. Excessive (≥300 μg/L) UIE was strongly associated with autoimmune thyroiditis. If the UIE level is ≥ 300 μg/L, then there is 17.94 times higher chance of having amiodarone-induced thyrotoxicosis than those who have UIE level < 300 μg/L (P < 0.001). Conclusions: A possible association between increased iodine intake and autoimmune thyroiditis was found in this study. Excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction.
Keywords: Hashimoto, iodine, thyroiditis
|How to cite this article:|
Palaniappan S, Shanmughavelu L, Prasad HK, Subramaniam S, Krishnamoorthy N, Lakkappa L. Improving iodine nutritional status and increasing prevalence of autoimmune thyroiditis in children. Indian J Endocr Metab 2017;21:85-9
|How to cite this URL:|
Palaniappan S, Shanmughavelu L, Prasad HK, Subramaniam S, Krishnamoorthy N, Lakkappa L. Improving iodine nutritional status and increasing prevalence of autoimmune thyroiditis in children. Indian J Endocr Metab [serial online] 2017 [cited 2017 Apr 27];21:85-9. Available from: http://www.ijem.in/text.asp?2017/21/1/85/195996
| Introduction|| |
Following the implementation of National Iodine Deficiency Disorders Control Programme based on Universal Salt Iodization (USI), there are reports of normalization of iodine nutrition as reflected by urinary iodine excretion (UIE) from the country., According to current recommendations by the World Health Organization, median urinary iodine concentration of 100–199 µg/L in samples from school children indicate adequate iodine intake and optimal iodine nutrition. The UIE is the primary indicator for a person's iodine nutritional status and the primary variable used to measure the success of iodine supplementation in a population.
It is well known that when a cohort is supplemented with iodine, the pattern of thyroid diseases is bound to undergo a definitive change. Many researchers from the western world began to observe an increase in Juvenile autoimmune thyroiditis (JAT) in populations who have been supplemented with iodine. Predominant studies in this arena are from the western world and population-based studies. Hence, we decided to perform this study to evaluate the link between excess iodine intake as evidenced by increased UIE and autoimmune thyroiditis in children and correlation between UIE and thyroid microsomal antibody (TMA) (thyroid peroxidase [TPO]) titers in children.
| Materials and Methods|| |
We conducted this study as a case–control study over a period of 3 years from February 2010 to February 2014. The study was initiated after institutional ethical committee approval. All children aged 6–12 years with goiter attending the pediatric endocrinology outpatient department were evaluated for autoimmune thyroiditis as per standard protocols. Goiter with autoimmune thyroiditis served as cases. Children with goiter but workup negative for autoimmune thyroiditis and iodine deficiency disorder were considered to be controls (one control per case recruited). Children with proven congenital hypothyroidism, iodine deficiency disorder, other endocrine disorder, and history of taking iodine-containing medications were excluded from the study. Children with goiter were subjected to blood tests for free thyroxine (FT4), thyroid stimulating hormone (TSH) and TPO antibody, fine needle aspiration was advised for all children with goiter. UIE was estimated in spot urine sample for both cases and controls. Definitions used in the study are shown in [Table 1].
The stained slides were reported blindly by a cytopathologist, who had no access to clinical and serological data. The criteria adopted for the diagnosis of autoimmune thyroiditis were: the presence of lymphocytic infiltrate, diminished colloid, and minimal to moderate follicular destruction, with or without Hürthle cell change.
T4 and TSH were estimated by enzyme immunoassay method. The normal range of FT4 as standardized in our laboratory was 7.3–13.4 pM/L and for TSH 0.5–5 µIU/mL. TMAs were tested by electrochemiluminescence assay (Cobas-Roche- Elecsys1010 analyzer), titers ≥ 34 IU/L were considered positive. Spot urine samples were collected in a wide-mouthed plastic container with tight screw tops and kept in a refrigerator at − 4°C after addition of 1 drop of toluene. Urine was digested with ammonium persulfate to get rid of interfering substances; then iodide was measured by its catalytic action on the reduction of ceric ammonium sulfate (yellow) to the cerous form (colorless), coupled to oxidation of arsenite to arsenate (Sandell–Kolthoff reaction).
Data were entered using Microsoft corp., Excel and analyzed using SPSS statistics for windows, version 20, Chicago, IL, USA. For continuous data mean with standard deviation and median were calculated. Mann–Whitney U-test was used to compare the difference between median UIE between cases and controls. Correlation between urinary iodine and antimicrosomal antibody (AMA) titers was analyzed by arriving at Pearson correlation coefficient (R value). Logistic regression was used to find the association between excess UIE levels, sex, family history of thyroid disease and autoimmune thyroiditis. All tests are considered statistically significant at P < 0.01.
| Results|| |
During the study, 91 children presented to the thyroid clinic with goiter. Of these, 4 children with mild iodine deficiency and 1 child with dyshormonogenesis were excluded from this study. Thus, 86 children (43 cases and controls each) satisfied the necessary criteria and were recruited into the study. The baseline demographic, clinical, biochemical parameters of the study population are depicted in [Table 2].
The study population was divided as per the iodine status as adequate, above adequate requirements, and excessive iodine status (median UIE 100–199 µg/L, 200–299 µg/L, and ≥300 µg/L, respectively). 9.3%, 16.3%, and 74.4% of cases fell in the adequate, above adequate, and excessive, respectively. The corresponding percentages in controls were: 62.8%, 23.3%, and 14%, respectively [Figure 1]a; P < 0.05]. The levels of urinary iodine were significantly higher in children with autoimmune thyroiditis as compared with controls (329.53 ± 80.813 vs. 214.30 ± 78.464 µg/L P < 0.001) [Figure 1]b.
|Figure 1: (a) Urinary iodine excretion levels in case and controls as per the World Health Organization definitions. (b) Comparison of mean urinary iodine excretion levels in cases and controls. *P < 0.05|
Click here to view
To elucidate the relationship between UIE and JAT, a correlation analysis was performed between UIE levels and AMA titers. A positive correlation between UIE and AMA titers (R = 0.503 and P < 0.001) among cases was observed [Figure 2].
|Figure 2: Depiction of correlation between thyroid microsomal antibody levels and urinary iodine excretion levels. R - 0.503, P < 0.05|
Click here to view
The factors associated with JAT: Age, UIE levels, sex, family history of thyroid disease was considered, and their independent influence over JAT analyzed by a logistic regression analysis. It was observed that the odds of having UIE level ≥ 300 µg/L is 17.94 in cases versus controls (odds ratio 17.94, 95% confidence interval 5.96–53.97 P < 0.001). None of the study subjects had hyperthyroidism.
| Discussion|| |
To the best of our knowledge, this is the first study investigating the impact of excessive iodine on thyroid autoimmunity in a clinic-based setting from South India. We observed 63.9% of the study sample to have higher than optimal UIE. Children with JAT had higher UIE levels. A significant correlation was observed between UIE levels and AMA titers in children with JAT.
In this study, 90.7% (n = 39) of the cases and 37.3% (n = 16) of the controls exhibited higher than optimal UIE. The high UIE of the present study may reflect a trend with time with improved penetration and execution of USI program. A possibility of nonsalt sources of iodine like domestic water filters, based on polyiodide resin technology can provide 3000–6000 µg of iodine per day to an individual, that could contribute to high UIE or it can be hypothesized due to the inability of the diseased thyroid to trap available iodine efficiently. This observation is in agreement with Marwaha et al. and Bazrafshan et al. However, one must remember that these were community-based studies and ours in a clinic-based study; hence, the element of referral bias must be taken into account.
The association between increased UIE and JAT has been supported by the previous studies;,,, refuted by Zimmermann, et al. and BacZyk, et al. We observed a significantly higher median Iodine levels in children with JAT versus children without (329.53 ± 80.813 vs. 214.30 ± 78.464 µg/L P < 0.001). This is in line with the study from North India by Gopalakrishnan, et al. (166 µg/L in children with JAT versus 133 µg/L in children without JAT, P < 0.05). However, Zois, et al. did not observe any difference in Median UIE in children with and without JAT. The possible explanations attributable to our observation include:
- Iodine toxicity hypothesis – Iodine undergoes peroxidation and generates free radicals and causes thyroid cell destruction ,
- Increased immunogenicity of the iodinated thyroglobulin 
- Direct stimulation of the immune system by the iodine.
We observed a weak, but significant correlation between UIE levels and TMA antibody titers (R = 0.501). A lack of correlation has been reported from a Srilankan study (R = 0.44, P = 0.3) and Zois, et al. The biological explanation to this observation would be that Iodine plays a permissive role, not causative role, in the background of genetic predisposition.
Based on logistic regression analysis, we observed that the odds of having UIE level ≥ 300 µg/L are 17.94 among children with JAT to those without. This is in agreement with the results of Zois et al. who concluded silent iodine prophylaxis resulted in the elimination of iodine deficiency in Greece, and this has been accompanied by an increase in the prevalence of autoimmune thyroiditis. However, Kaloumenou observed family history, female sex as strong determining factors for the occurrence of JAT, over excessive iodine intake. It is also interesting to note that none of our subjects developed hyperthyroidism during the study. Iodine-induced hyperthyroidism related to thyroid autonomy has been reported previously., Whether this is related to small sample size or genetic factors that merit further exploration cannot be answered at this point of time.
We wish to clarify certain issues pertaining to the methodology adopted in the study. We applied both serological and cytomorphological criteria to diagnose autoimmune thyroiditis. It is recognized that antibody titers might change, but cytomorphological features persist during the clinical course of amiodarone-induced thyrotoxicosis (AIT) indicating the need to combine cytological and serological evaluation to diagnose AIT. Furthermore, we have selected only prepubertal subjects for the study purpose to eliminate the immune modulatory effects of pubertal hormones on antibody titers. Previous studies have considered children with negative antibody titers as controls. Considering ethical issues, we included children with simple colloid goiter as controls as an estimation of anti-TMA titers and urine iodine would be a part of the routine evaluation of the condition.
Our study is not without limitations. Ours is aclinic-based study, not a community-based one, which would be ideal. Lack of periodization data does not permit the conclusion that high value of iodine in AIT is due to salt iodization. Salt iodine content was not estimated, and the amount of salt consumption was not quantified in this study.
| Conclusions|| |
We observed a possible association between increased iodine intake and autoimmune thyroiditis. Excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction. Proper monitoring of the salt iodization program is essential to achieve acceptable iodine status. If a causal relationship is established by future research, then supplementation programs can be tailored to the need of the particular region.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kapil U, Singh P. Current status of urinary iodine excretion levels in 116 districts of India. J Trop Pediatr 2004;50:245-7.
Kapil U, Singh P, Pathak P. Current status of iodine nutriture and iodine content of salt in Andhra Pradesh. Indian Pediatr 2004;41:165-9.
WHO/UNICEF/ICCIDD. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination. WHO Document WHO/NHD/01.1. Geneva: World Health Organization; 2001.
WHO/UNICEF/ICCIDD. Indicators for assessing iodine deficiency disorders and their control through salt iodization. WHO Document WHO/NUT/94.6. Geneva: World Health Organization; 1994.
Muirhead S. Diagnostic approach to goitre in children. Paediatr Child Health 2001;6:195-9.
Orell SR, Philips J. The thyroid. Fine needle biopsy and cytological diagnosis of thyroid lesions. Monogr Clin Cytol 1997;14:VII: 61-184.
Ohashi T, Yamaki M, Pandav CS, Karmarkar MG, Irie M. Simple microplate method for determination of urinary iodine. Clin Chem 2000;46:529-36.
Delange F, de Benoist B, Burgi H; ICCIDD Working Group. Determining median urinary iodine concentration that indicates adequate iodine intake at population level. Bull World Health Organ 2002;80:633-6.
Kapil U, Prakash S, Nayar D, Ramachandran S, Vashist M, Balamurugan A, et al
. Addition of iodine to water by a filter based on polyiodide resin technology used at household level. J Assoc Physicians India 1998;46:209-10.
Marwaha RK, Tandon N, Desai A, Kanwar R, Mani K. Iodine nutrition in upper socioeconomic school children of Delhi. Indian Pediatr 2010;47:335-8.
Bazrafshan HR, Mohammadian S, Ordookhani A, Farhidmehr F, Hedayati M, Abdolahi N, et al
. Prevalence of goiter among schoolchildren from Gorgan, Iran, a decade after national iodine supplementation: Association with age, gender, and thyroperoxidase antibodies. J Endocrinol Invest 2005;28:727-33.
Markou KB, Georgopoulos NA, Makri M, Vlasopoulou B, Anastasiou E, Vagenakis GA, et al
. Improvement of iodine deficiency after iodine supplementation in schoolchildren of Azerbaijan was accompanied by hypo and hyperthyrotropinemia and increased title of thyroid autoantibodies. J Endocrinol Invest 2003;26 2 Suppl:43-8.
Teng X, Shan Z, Chen Y, Lai Y, Yu J, et al
. More than adequate iodine intake may increase subclinical hypothyroidism and autoimmune thyroiditis: a cross-sectional study based on two Chinese communities with different iodine intake levels. Eur J Endocrinol 2011;164:943-50.
Pedersen IB, Laurberg P, Knudsen N, Jørgensen T, Perrild H, Ovesen L, et al. An increased incidence of overt hypothyroidism after iodine fortification of salt in Denmark: A prospective population study. J Clin Endocrinol Metab 2007;92:3122-7.
Teng W, Shan Z, Teng X, Guan H, Li Y, Teng D, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med 2006;354:2783-93.
Zimmermann MB, Moretti D, Chaouki N, Torresani T. Introduction of iodized salt to severely iodine-deficient children does not provoke thyroid autoimmunity: A one-year prospective trial in Northern Morocco. Thyroid 2003;13:199-203.
Baczyk M, Ruchala M, Pisarek M, Pietz L, Junik R, Sowinski J, et al. Changes in thyroid morphology and function in children in Western Poland as a result of intensified iodine prophylaxis. J Pediatr Endocrinol Metab 2007;20:511-5.
Gopalakrishnan S, Singh SP, Prasad WR, Jain SK, Ambardar VK, Sankar R. Prevalence of goitre and autoimmune thyroiditis in schoolchildren in Delhi, India, after two decades of salt iodisation. J Pediatr Endocrinol Metab 2006;19:889-93.
Zois C, Stavrou I, Kalogera C, Svarna E, Dimoliatis I, Seferiadis K, et al. High prevalence of autoimmune thyroiditis in schoolchildren after elimination of iodine deficiency in Northwestern Greece. Thyroid 2003;13:485-9.
Vitale M, Di Matola T, D'Ascoli F, Salzano S, Bogazzi F, Fenzi G, et al. Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 2000;141:598-605.
Sundick RS, Herdegen DM, Brown TR, Bagchi N. The incorporation of dietary iodine into thyroglobulin increases its immunogenicity. Endocrinology 1987;120:2078-84.
Dai YD, Rao VP, Carayanniotis G. Enhanced iodination of thyroglobulin facilitates processing and presentation of a cryptic pathogenic peptide. J Immunol 2002;168:5907-11.
Weetman AP, McGregor AM, Campbell H, Lazarus JH, Ibbertson HK, Hall R. Iodide enhances IgG synthesis by human peripheral blood lymphocytes in vitro. ActaEndocrinol (Copenh) 1983;103:210-5.
Kaloumenou I, Mastorakos G, Alevizaki M, Duntas LH, Mantzou E, Ladopoulos C, et al. Thyroid autoimmunity in schoolchildren in an area with long-standing iodine sufficiency: Correlation with gender, pubertal stage, and maternal thyroid autoimmunity. Thyroid 2008;18:747-54.
Stanbury JB, Ermans AE, Bourdoux P, Todd C, Oken E, Tonglet R, et al. Iodine-induced hyperthyroidism: Occurrence and epidemiology. Thyroid 1998;8:83-100.
Delange F, de Benoist B, Alnwick D. Risks of iodine-induced hyperthyroidism after correction of iodine deficiency by iodized salt. Thyroid 1999;9:545-56.
Mäenpää J, Raatikka M, Räsänen J, Taskinen E, Wager O. Natural course of Juvenile autoimmune thyroiditis. J Pediatr 1985;107:898-904.
[Figure 1], [Figure 2]
[Table 1], [Table 2]