|Year : 2018 | Volume
| Issue : 2 | Page : 75-79
Impact of iodine nutrition status on thyroid autoimmunity in subclinical hypothyroid patients attending a tertiary hospital of Bangladesh
Md Asaduzzaman1, A B M Kamrul-Hasan2, A K M Aminul-Islam3, Md Rafiq-Uddin4, MA Hasanat5, Md Fariduddin5
1 Resident Physician, Shaheed Sheikh Abu Naser Specialized Hospital, Khulna, Bangladesh
2 Department of Endocrinology, Mymensingh Medical College Hospital, Mymensingh, Bangladesh
3 Department of Endocrinology, Colonel Abdul Malek Medical College, Manikganj, Bangladesh
4 Department of Endocrinology, Chittagong Medical College Hospital, Chittagong, Bangladesh
5 Department of Endocrinology, BSMMU, Dhaka, Bangladesh
|Date of Web Publication||17-Jul-2018|
Shaheed Sheikh Abu Naser Specialized Hospital, Khulna-9000
Source of Support: None, Conflict of Interest: None
Background: Iodine excess may trigger thyroid autoimmunity. The aim of this study was to observe the iodine nutrition status in thyroid autoantibody-positive and -negative subclinical hypothyroid (SCH) patients.
Materials and Methods: This cross-sectional study enrolled 99 SCH patients (50 thyroid autoantibody-positive and 49 autoantibody-negative) aging 18–65 years from June 2014 to April 2015. Serum free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase (TPO), and anti-thyroglobulin (TG) antibodies were measured; the urinary iodine concentration (UIC) was estimated and the iodine nutrition status was categorized (deficiency, optimal, more than optimal, and excessive) according to urinary iodine levels by WHO/UNICEF/ICCIDD recommended cutoffs. Statistical analysis was performed by using IBM SPSS Statistics for Windows, version 23.0 software. P ≤≤0.05 was considered to be statistically significant.
Results: The antibody-positive SCH subjects had a higher mean (299.03 ± 19.43 vs. 263.54 ± 23.10, mean ± standard error of mean, P = 0.314) and median (295.85 vs. 212.70, P = 0.035) UIC than antibody-negative ones. Although there was no statistical difference in the frequency of antibody-positive and antibody-negative status among various subgroups of iodine status (χ2 = 4.941, P = 0.176); the anti-TG titer showed significant statistical difference among the subgroups (P = 0.047) and was the highest in patients having excessive iodine. The frequency of goiter was also higher in patients having over sufficient (more than optimal and excessive) UIC (P = 0.905). UIC did not significantly correlate with serum TSH, FT4 levels, and anti-TPO titer but had a significant positive correlation with anti-TG titer (r = 0.292, P = 0.003).
Conclusion: Over sufficient state of UI may be related to the thyroid autoimmunity and goiter in SCH patients.
Keywords: Iodine nutrition status, subclinical hypothyroidism, thyroid autoimmunity
|How to cite this article:|
Asaduzzaman M, Kamrul-Hasan A B, Aminul-Islam A K, Rafiq-Uddin M, Hasanat M A, Fariduddin M. Impact of iodine nutrition status on thyroid autoimmunity in subclinical hypothyroid patients attending a tertiary hospital of Bangladesh. Thyroid Res Pract 2018;15:75-9
|How to cite this URL:|
Asaduzzaman M, Kamrul-Hasan A B, Aminul-Islam A K, Rafiq-Uddin M, Hasanat M A, Fariduddin M. Impact of iodine nutrition status on thyroid autoimmunity in subclinical hypothyroid patients attending a tertiary hospital of Bangladesh. Thyroid Res Pract [serial online] 2018 [cited 2019 Jun 15];15:75-9. Available from: http://www.thetrp.net/text.asp?2018/15/2/75/236811
| Introduction|| |
Iodine is an essential raw material for thyroid hormone synthesis. The minimum daily iodine intake that will maintain normal thyroid function is 150 μg in adults. Iodine deficiency can result in goiter and hypothyroidism. On the other hand, excess iodine intake may also lead to thyroid dysfunction as iodine exerts some effects on the normal and the sick thyroid gland. Epidemiological studies have found a higher incidence of subclinical hypothyroidism and autoimmune thyroiditis in areas with higher dietary iodine intake than in areas with subnormal or normal dietary iodine intake.,
In 1990, the goal of the World Summit for Children at the United Nations was to eliminate iodine deficiency diseases and recommended universal salt iodization (USI) as the main strategy. The introduction of iodine fortification of salt and the appearance of various iodine fortifications in food greatly improved the iodine nutritional status worldwide including Bangladesh. Iodine supplementation should be carefully monitored to ensure adequate iodine intake while avoiding iodine excess which is currently a more frequent occurrence than iodine deficiency as reflected by the WHO data showing that over 30 countries worldwide having more than adequate or excessive iodine intake.,
Data relating iodine status and thyroid autoimmunity is scarce, and no data are available in our perspective, particularly in the context of subclinical hypothyroidism about urinary iodine. This study was planned to observe the iodine nutrition status in biochemically proved antibody-positive and antibody-negative subclinical hypothyroid (SCH) patients.
| Materials and Methods|| |
This cross-sectional study enrolled 99 SCH patients (50 thyroid autoantibody positive and 49 thyroid autoantibody negative) aging 18–65 years recruited from the outpatient Department of Endocrinology of a tertiary level hospital of Bangladesh from June 2014 to April 2015. The Institutional Review Board of institute approved the protocol of the study. Samples were selected by consecutive purposive nonprobability basis. Subclinical hypothyroidism was defined as raised serum thyroid stimulating hormone (TSH) level (>5.5 μIU/ml) with normal free thyroxine (FT4) level (0.8–1.8 ng/dl). Pregnant and lactating mother, the patient taking drugs that may interfere thyroid function (e.g., amiodarone, lithium), patients with current or recent severe acute illness, patients with other chronic autoimmune diseases or chronic debilitating conditions were excluded. After taking informed written consent, all patients were interviewed for and examined for relevant clinical information. A volume of 5 mL of venous blood sample was collected from all. Analysis of FT4, TSH, anti-thyroid peroxidase (TPO), and anti-thyroglobulin (TG) antibodies was done using the chemiluminescent sequential immunometric assay with IMMULITE 2000 system analyzers. Five mL spot urine sample was collected from each subject in screw-capped deiodinized plastic cups and transferred to tightly sealed deiodinized tubes and preserved under − 20°C in a refrigerator until analysis. The urinary iodine content was estimated using the wet digestion method of Dunn et al. with modification of Sandell and Kolthoff. The iodine nutrition status was categorized according to urinary iodine levels according to the WHO/UNICEF/ICCIDD recommended cutoffs (excessive: ≥300 μg/L, more than optimal: 200–299 μg/L, optimal: 100–199 μg/L, deficiency: <100 μg/L).
Statistical analysis was performed using IBM SPSS Statistics for Windows, version 23.0 (IBM Corp., Armonk, NY, USA) software. The categorical variables were represented as percentages and measurable variables as mean ± standard deviation or mean ± standard error of the mean (SEM) and median. Student's t-test, Chi-square test, one-way ANOVA, and Mann–Whitney test were performed for comparing the variables between different groups as appropriate. Pearson's correlation test was used to observe correlation among different variables (urinary iodine concentration [UIC], age, TSH, FT4, anti-TPO titer, and anti-TG titer). P ≤0.05 was considered to be statistically significant.
| Results|| |
In this cross-sectional study, 99 cases of subclinical hypothyroidism were included, among them, 50 were positive for thyroid autoantibody, and 49 were negative for thyroid autoantibody.
General characteristics of the study participants are shown in [Table 1]. Their mean age was 36 ± 10.93 years; the ratio of male and female was 1:6.6. Nearly 97% of the respondents consumed iodized salt though only 62.6% were aware of the necessity of dietary iodine intake. The majority (86.9%) had no family history of thyroidal diseases.
The mean, median and inter-quartile ranges of UIC of antibody positive and antibody negative SCH subjects are shown in [Table 2]. The antibody-positive subjects had a higher mean (299.03 ± 19.43 vs. 263.54 ± 23.10, mean ± SEM, P = 0.314) and median (295.85 vs. 212.70, P = 0.035). UIC than antibody-negative ones. [Table 3] compares the frequency of antibody-positive and antibody-negative status among various subgroups of urinary iodine status showing no statistical difference among the subgroups.
|Table 2: Urinary iodine (mean±standard error of mean, median) in the subjects with or without thyroid auto-immunity|
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|Table 3: Urinary iodine status (µg/L) among subjects with or without positive thyroid auto-antibody|
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Comparison of goiter frequency; TSH, FT4, anti-TPO and anti-TG levels among subjects with various degrees of iodine status are shown in [Table 4]. Only serum-free T4 level and anti-TG titer showed statistical difference among the subgroups of iodine nutrition status.
|Table 4: Comparison of goiter frequency, thyroid stimulating hormone, free thyroxine and thyroid autoantibodies among various degrees of iodine status|
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Correlations of UIC with other variables are shown in [Table 5]. UIC did not significantly correlate with the age of the subjects, serum TSH, FT4 levels and anti-TPO titer but had a significant positive correlation with anti-TG titer (r = 0.292, P = 0.003).
| Discussion|| |
In the present study, it was clearly observed that more than 60% (23% more than adequate, 41% excessive) of the subjects suffering from SCH have iodine status to be considered as more than sufficient, one-quarter has adequate iodine level and around 10% seems deficient with iodine nutrition as judged on the basis of recommended cutoff values. SCH subjects who were positive for thyroid autoantibody tend to have the higher mean and median UIC than their autoantibody negative counterparts. The frequency of goiter was relatively higher, though not statistically significant, in the subjects with more than sufficient urinary iodine than those for groups with adequate or deficient iodine status. Although TSH level was almost similar in all groups, it tends to be higher in excessive iodine group.
In 1989, the Government of Bangladesh passed a law making it mandatory for all edible salt to be iodized. Fortification of salt with iodine was initiated in 1990 and success of the program was revealed by a UNICEF survey in 1999, which indicated that the proportion of households consuming iodized salt had risen to 71%. Another survey in 2004-2005 also found normal median UIC in rural women and children (123 μg/L and 141 μg/L respectively) though in urban women and children were found to have more than adequate median UIC (230 μg/L and 229 μg/L, respectively).
Holding the cutoff as UIC 200 μg/L for more than sufficient, this study observed that 64% of the studied subjects were more than sufficient with iodine nutrition status. The observed median and mean urinary iodine in the antibody-positive and antibody-negative groups as well as total subjects were more than 200 μg/L. These findings are in agreement with some studies in Bangladesh and some other countries which observed improvements in iodine nutrition status and also more than normal iodine status after implementation of USI.,,,, Thus, it seems pertinent to suspect that as part of the national iodization program, overall urinary iodine status might have been improved but warrant for watching over the predisposition of thyroid autoimmunity.
Although the mechanisms are not fully elucidated, excess iodine is a well-recognized environmental factor for autoimmune thyroid disease. Thyroid autoimmunity may be related to over sufficient status of urinary iodine has been apprehended by many investigators.,,, Totally, three mechanisms have been assumed for the development of iodine-induced autoimmune thyroiditis. First, iodine intake increases the immunogenicity of TG, thereby precipitating an autoimmune process at both the T- and B-cell level. Second, iodine has a toxic effect on thyroid cells. Third, iodine directly stimulates immune and immunity-related cells.
In Japan, the incidence of autoimmune thyroiditis was found to be higher in areas with high dietary iodine intake than in areas with normal dietary iodine intake; the prevalence of positive thyroid autoantibodies was also found to be higher in subjects with more than adequate iodine intake than in those with adequate iodine intake. Alsayed et al. observed that the levels of urinary iodine were significantly higher in Egyptian patients with SCH as compared with healthy controls; and in patients with SCH, there was a significant correlation between UIC and TPOAb levels. Bastemir et al. found the prevalence of antithyroid antibody (anti-TG and/or anti-TPO) positivity was significantly higher in people from an iodine-sufficient area than those from an iodine-deficient area of Turkey. A Greek study also found that the administration of iodized oil to patients with small nontoxic goiter in an iodine-replete area was accompanied by the development of abnormal levels of ThAbs in some cases and by an increase in thyroid lymphocytic infiltration.
In the background of observed sufficiency and over sufficient status of UI, it is not possible to clearly predict the matter of iodine excess and autoimmunity in small-scale cross-sectional study like the present one, whereupon even it is not clear whether iodine nutrition status has been sustained in the individuals for certain period to trigger autoimmunity. However, it is observed that frequency of antithyroid antibody positivity was higher in subjects with excessive UI status though it was not statistically significant. Although both the antibody-positive group and antibody negative group showed mean and median UI level greater than the upper limit of sufficiency, the median UIC was significantly higher in antibody positive group. Thus, it is not possible to make any inference nor possible to assume over the link of high iodine and autoimmunity in the studied patients unless they are followed periodically for their iodine and antibody status. Some studies observed a positive correlation of UI with antithyroid antibodies while others did not.,,, The present study also observed a positive correlation of UI with anti-TG but not with anti-TPO. It was interesting to observe that overall positivity of antibody status was higher in the adequate than the deficient UI status, and further higher in the excessive group than that of the deficient, adequate and more than adequate groups. All these indicate a strong possibility for assuming predisposition of autoimmunity with high status of UI. A long-term follow-up with SCH patients for autoimmunity and iodine status can hopefully be able to resolve the issue of controversy.
Although autoimmunity may have increased following universal iodization of salt, as per reports of observational studies mentioned earlier, it is important to reiterate the benefits of eradicating iodine deficiency related thyroid diseases and mental retardation that affected a large population across the globe. The increase in autoimmune thyroid disorders that can be managed easily may only be partially contributed to by the increasing urine iodine concentrations as evidenced in this study with both TPO negative and positive patients having similar UIC (statistically and numerically insignificant). Even for the relationship between UIC and anti-TG, the r value is only 0.29, suggesting a weak positive correlation between the two parameters.
The frequency of goiter was higher in more than adequate and excessive iodine group than in the deficient and adequate iodine groups, but this observation differs with others., This is contrary to the common belief of disappearance of goiter with sufficient iodine nutrition status. Rather, excess iodine status may be linked to the persistence of goiter.
The study had several limitations. This was a single-center study, and the sample size was small. No healthy control group was taken which might have diluted the importance of comparisons and observations. UIC of patients having other categories of abnormal thyroid functions was also not considered. The iodine content of the patients' household table salt was also not measured.
| Conclusion|| |
This small hospital-based study investigated UI status in SCH patients with an aim to see the relationship of UI status with antithyroid antibodies in these patients. It was observed that iodine nutrition status of SCH patients is mostly more than adequate or excess and a very few are deficient. It may be the consequence and beneficial effect of USI throughout the country. Over sufficient state of UI may be related to the autoimmunity and goiter observed in SCH. Long-term studies with periodic follow-up on antithyroid antibodies and urinary iodine may be helpful for the further understanding of the issue.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Barret KE, Barman SM, Boitano S, Brooks HL. Ganong's Review of Medical Physiology. 24th
ed. New York: The McGraw-Hill Companies, Inc.; 2012. p. 340-1.
Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet 2008;372:1251-62.
Laurberg P, Bülow Pedersen I, Pedersen KM, Vestergaard H. Low incidence rate of overt hypothyroidism compared with hyperthyroidism in an area with moderately low iodine intake. Thyroid 1999;9:33-8.
Konno N, Makita H, Yuri K, Iizuka N, Kawasaki K. Association between dietary iodine intake and prevalence of subclinical hypothyroidism in the coastal regions of Japan. J Clin Endocrinol Metab 1994;78:393-7.
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.
WHO/UNICEF/ICCIDD. Indicators for Assessing Iodine Deficiency Disorders and their Control through Salt Iodization. WHO/NUT/94.6. Geneva: WHO; 1994. p. 1-55.
Zimmermann MB. Iodine deficiency and excess in children: Worldwide status in 2013. Endocr Pract 2013;19:839-46.
Zimmermann MB, Andersson M. Update on iodine status worldwide. Curr Opin Endocrinol Diabetes Obes 2012;19:382-7.
Dunn JT, Crutchfield HE, Gutekunst R, Dunn AD. Two simple methods for measuring iodine in urine. Thyroid 1993;3:119-23.
WHO, UNICEF, ICCIDD. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination, a Guide for Programme Managers. 3rd
ed. Geneva: WHO; 2007. Available from: http://www.who.int/nutrition/publications/micronutrients/iodine_deficiency/9789241595827/en/. [Last accessed on 2015 Feb 16].
UNICEF/Bangladesh/Our Work/Health and Nutrition/Nutrition/Salt Iodization. Available from: https://www.unicef.org/bangladesh/health_nutrition_409.htm. [Last accessed on 2018 Mar 03].
Yusuf HK, Rahman AK, Chowdhury FP, Mohiduzzaman M, Banu CP, Sattar MA, et al
. Iodine deficiency disorders in Bangladesh, 2004-2005: Ten years of iodized salt intervention brings remarkable achievement in lowering goiter and iodine deficiency among children and women. Asia Pac J Clin Nutr 2008;17:620-8.
Teng X, Shan Z, Chen Y, Lai Y, Yu J, Shan L, 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.
Alsayed A, Gad AM, Abdel-Baset H, Abdel-Fattah A, Ahmed A, Azab A, et al.
Excess urinary iodine is associated with autoimmune subclinical hypothyroidism among Egyptian women. Endocr J 2008;55:601-5.
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.
Duntas LH. Environmental factors and autoimmune thyroiditis. Nat Clin Pract Endocrinol Metab 2008;4:454-60.
Papanastasiou L, Alevizaki M, Piperingos G, Mantzos E, Tseleni-Balafouta S, Koutras DA, et al.
The effect of iodine administration on the development of thyroid autoimmunity in patients with nontoxic goiter. Thyroid 2000;10:493-7.
Fountoulakis S, Philippou G, Tsatsoulis A. The role of iodine in the evolution of thyroid disease in Greece: From endemic goiter to thyroid autoimmunity. Hormones (Athens) 2007;6:25-35.
Bastemir M, Emral R, Erdogan G, Gullu S. High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents after elimination of iodine deficiency in the eastern black sea region of Turkey. Thyroid 2006;16:1265-71.
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]