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Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Department of Internal Medicine, Copenhagen University Hospital – Herlev and Gentofte, Copenhagen, Denmark
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Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild–moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program – as IF – is initiated.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
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Department of Biotechnology and Translational Medicine, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
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Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
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Center for Interdisciplinary Research on Medicines (C.I.R.M.), University of Liege (ULiège), CHU (B35), Liege, Belgium
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Objective
The aim was to evaluate the possible association between some endocrine disruptive chemicals and thyroid cancer (TC) in an Italian case–control cohort.
Methods
We enrolled 112 TC patients and 112 sex- and age-matched controls without known thyroid diseases. Per- and poly-fluoroalkyl substances (PFAS), poly-chlorinated biphenyls (PCBs), and dichlorodiphenyltrichloroethane (4,4′-DDT and 4,4′-DDE) were measured in the serum by liquid or gas chromatography–mass spectrometry. Unconditional logistic regression, Bayesan kernel machine regression and weighted quantile sum models were used to estimate the association between TC and pollutants’ levels, considered individually or as mixture. BRAF V600E mutation was assessed by standard methods.
Results
The detection of perfluorodecanoic acid (PFDA) was positively correlated to TC (OR = 2.03, 95% CI: 1.10–3.75, P = 0.02), while a negative association was found with perfluorohexanesulfonic acid (PFHxS) levels (OR = 0.63, 95% CI: 0.41–0.98, P = 0.04). Moreover, perfluorononanoic acid (PFNA) was positively associated with the presence of thyroiditis, while PFHxS and perfluorooctane sulfonic acid (PFOS) with higher levels of presurgical thyroid-stimulating hormone (TSH). PFHxS, PFOS, PFNA, and PFDA were correlated with less aggressive TC, while poly-chlorinated biphenyls (PCB-105 and PCB-118) with larger and more aggressive tumors. Statistical models showed a negative association between pollutants’ mixture and TC. BRAF V600E mutations were associated with PCB-153, PCB-138, and PCB-180.
Conclusion
Our study suggests, for the first time in a case–control population, that exposure to some PFAS and PCBs associates with TC and some clinical and molecular features. On the contrary, an inverse correlation was found with both PFHxS and pollutants’ mixture, likely due to a potential reverse causality.
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Global warming is now universally acknowledged as being responsible for dramatic climate changes with rising sea levels, unprecedented temperatures, resulting fires and threatened widespread species loss. While these effects are extremely damaging, threatening the future of life on our planet, one unexpected and paradoxically beneficial consequence could be a significant contribution to global iodine supply. Climate change and associated global warming are not the primary causes of increased iodine supply, which results from the reaction of ozone (O3) arising from both natural and anthropogenic pollution sources with iodide (I−) present in the oceans and in seaweeds (macro- and microalgae) in coastal waters, producing gaseous iodine (I2). The reaction serves as negative feedback, serving a dual purpose, both diminishing ozone pollution in the lower atmosphere and thereby increasing I2. The potential of this I2 to significantly contribute to human iodine intake is examined in the context of I2 released in a seaweed-abundant coastal area. The bioavailability of the generated I2 offers a long-term possibility of increasing global iodine status and thereby promoting thyroidal health. It is hoped that highlighting possible changes in iodine bioavailability might encourage the health community to address this issue.
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Graphical abstract
Abstract
In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g. hand disinfectants, disinfection of animals’ teats/udder, embalming fluids before cremation) that contain molecular iodine (I2), entirely neglecting the 2013 ECHA Regulation (EU) no. 528/2012 describing iodine as being of ‘great importance for human health’. Clearly, the current sweeping and erroneous classification of ‘iodine’ as an endocrine disruptor is ill-advised. We moreover call upon the scientific and medical community at large to use the accurate scientific nomenclature, i.e. iodide or iodate instead of ‘iodine’ when referring to iodized salts and food prepared there with. Drugs, diagnostic agents, and synthetic chemicals containing the element iodine in the form of covalent bonds must be correctly labeled ‘iodinated’, if possible, using each time their distinctive and accurate chemical or pharmacological name.
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Background
Intake of potassium iodide (KI) reduces the accumulation of radioactive iodine in the thyroid gland in the event of possible contamination by radioactive iodine released from a nuclear facility. The World Health Organization (WHO) has stated the need for research for optimal timing, appropriate dosing regimen, and safety for repetitive iodine thyroid blocking (ITB). The French PRIODAC project, addressed all these issues, involving prolonged or repeated releases of radioactive iodine. Preclinical studies established an effective dose through pharmacokinetic modeling, demonstrating the safety of repetitive KI treatment without toxicity.
Summary
Recent preclinical studies have determined an optimal effective dose for repetitive administration, associated with pharmacokinetic modeling. The results show the safety and absence of toxicity of repetitive treatment with KI. Good laboratory practice level preclinical studies corresponding to individuals >12 years have shown a safety margin established between animal doses without toxic effect. After approval from the French health authorities, the market authorization of the two tablets of KI, 65 mg/day, was defined with a new dosing scheme of a daily repetitive intake of the treatment up to 7 days unless otherwise instructed by the competent authorities for all categories of population except pregnant women and children under the age of 12 years.
Conclusion
This new marketed authorization resulting from scientific-based evidence obtained as part of the PRIODAC project may serve as an example to further harmonize the application of KI for repetitive ITB in situations of prolonged radioactive release at the European and international levels, under the umbrella of the WHO.
Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea
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Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul, Republic of Korea
Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea
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Environmental Health Center, Seoul National University College of Medicine, Seoul, Republic of Korea
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Department of Internal medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea
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Department of Internal medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
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Department of Pediatrics, Seoul National University College of Medicine, Seoul, Republic of Korea
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Objective
Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea.
Methods
Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100–299 μg/L), mild excess (300–499 μg/L), moderate excess (500–999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references.
Results
The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1–9.2) and aOR = 3.1 (95% CI: 1.2–8.3), respectively; age-specific criteria) than the iodine-adequate group.
Conclusions
Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.
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Background
Iodine deficiency disorder (IDD) is a major public health problem in Ethiopia. The availability of adequate iodized dietary salt at the household level is immensely important. Hence, this review aimed to estimate the pooled prevalence of adequate iodine concentration level of iodized dietary salt at the household level and its associated factors in Ethiopia.
Methods
We searched the literature using electronic databases (PubMed/Medline, Google Scholar, Science Direct, and Embase) and gray literature from January 9, 2022, to February 25, 2022. The rapid test kit was used to measure the adequacy of iodine level of dietary salt. The quality of studies was assessed using Joanna Briggs Institute critical appraisal tool. Heterogeneity between studies was checked using I2 test statistics and publication bias was checked using funnel plot and Egger’s statistical test at a 5% significance level. A random-effects model was employed to estimate the pooled prevalence of the outcome variable and its determinants in Ethiopia.
Results
The search identified 149 studies of which 18 studies were included with a total of 10,556 participants. The pooled prevalence of adequate iodine levels of iodized salt in Ethiopia was 44.37% (95% CI: 35.85-52.88). Women who had formal education (adjusted odds ratio (AOR) = 1.99 (95% CI: 1.47–2.48)), good knowledge of women (AOR = 2.14, 95% CI: 1.36–3.36), packed iodized salt (AOR = 3.85 (95% CI: 1.88–7.87)) and storage of iodized salt at home for less than 2 months (AOR = 2.66 (95% CI: 2.11–3.35) were the significant factors.
Conclusion
This review suggests that the pooled prevalence of adequate iodine levels was low. Our finding highlights the need for considering the educational status, knowledge, and duration of salt storage to enhance the prevalence of adequate levels of iodized salt at the national level.
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Thyroid hormones are essential for the metabolism of vertebrates and their synthesis, storage and release in the thyroid gland are orchestrated by their large protein precursor thyroglobulin (Tg). Alterations of Tg structure and localisation often correlate with major thyroid disorders. Namely, Tg is the main antigen in autoimmune thyroid diseases, and mutations in its gene are one of the causes of congenital hypothyroidism. Post-translational modifications (PTMs) are crucial for Tg surface properties and may be affected by the disease microenvironment; yet, their role in thyroid homeostasis and pathogenesis remains elusive. The advance of electron cryo-microscopy (cryo-EM) has recently enabled the structure of Tg to be revealed in the un-iodinated and iodinated states. Moreover, ad hoc proteomic analyses have lately identified new PTMs in Tg. Here, we provide an overview of the Tg cryo-EM models obtained so far, and we build a three-dimensional map of known PTMs in Tg. Based on their location, we suggest the potential implication of each PTM in hormonogenesis, interactions with cellular partners, colloid cross-linking and hormone release. In addition, several PTMs overlap with immunogenic regions and pathogenic gene mutations. Hence, our analysis reveals a possible cross-talk between PTMs and alteration of Tg function in these disorders. In perspective, multi-omics analyses from patients, interpreted with structural and functional data, may generate more robust models to correlate phenotypes with classes of Tg functional alterations. This integrative approach will likely provide more targeted strategies to restore specific Tg functions in different thyroid pathologies.
Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
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Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Heping District, Shenyang, Liaoning, China
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Department of Endocrinology, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China
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Objective
Central sensitivity of thyroid hormone refers to the sensitivity of hypothalamic–pituitary–thyroid (HPT) axis to the change in circulating free thyroxine (fT4). A complex relationship exists between thyroxine levels and iodine nutritional status. To explore the relationship between thyroid hormone sensitivity and iodine nutritional status in elevated thyrotropin (TSH), we used national data to assess the relationship between thyroid hormone sensitivity and iodine nutritional status with contrasting demographic characteristics in China.
Methods
We enrolled 12,197 participants with TSH > 4.2 mIU/L from China. Serum and urine samples were collected, and we measured serum fT4, TSH, thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels and urinary iodine concentration (UIC). The thyroid hormone sensitivity indices were calculated based on fT4 and TSH. The thyroid feedback quantile-based index (TFQI) is a new index to reflect thyroid hormone sensitivity. Higher TFQI quartiles indicated lower thyroid hormone sensitivity.
Results
The odds ratios (ORs) for the fourth versus first TFQI quartile were 0.84 (95% CI 0.72–0.99) for iodine deficiency, 1.24 (95% CI 1.05–1.47) for TPOAb+, and 0.44 (95% CI 0.40–0.50) for females. The OR of the fourth and first TFQI quartiles for age <30 years and >60 years was 2.09 (95% CI 1.82–2.41) and 1.19 (95% CI 1.05–1.36), respectively (P < 0.05). Other thyroid sensitivity indices also yielded similar results.
Conclusion
Thyroid hormone sensitivity and age have a U-shaped association in individuals with elevated TSH. Increased thyroid hormone sensitivity is associated with iodine deficiency and the female gender. Decreased thyroid hormone sensitivity is associated with TPOAb+. These findings are interesting and potentially useful for understanding the interaction between iodine nutrition and the hypothalamic–pituitary–thyroid axis.
