Oral Contraceptive Intake and Iodine Status in Young Women.

OBJECTIVE: Similar to pregnant women, women taking an oral contraceptive (OC) might have elevated iodine requirements due to the altered hormonal state. This is the first study aimed at investigating the prevalence of iodine deficiency and possible influences of OC intake on urine creatinine and iodine levels in young women. METHODS: One hundred fifty-five women between the age of 18 and 35 years (62 taking an OC and 93 controls) participated in a cross-sectional pilot study at the Medical University of Vienna, which included a 1-spot urine sample and a questionnaire on OC intake as well as a food questionnaire. RESULTS: The median urinary iodine concentration (UIC) in this study was 68 µg/L (41, 111 µg/L) suggesting an inadequate iodine status in the women according to the WHO guidelines. Median UIC (OC: 89 µg/L, IQR 55-120; control: 59 µg/L, IQR 39-91, p = 0.010) and urine creatinine (OC: median = 99.0 µg/L, IQR 74.9-175.5; control: 77.0 µg/L, IQR 49.6-147.2, p = 0.030) levels were significantly higher in OC women than in the control group. UIC corrected for urine creatinine was comparable between both groups. CONCLUSION: With similar creatinine-corrected UICs in both groups, OC intake might not have a significant impact on iodine status. However, the low median UIC in a vulnerable group of young women potentially conceiving in the following years points at the necessity of optimizing the iodine intake in the Austrian population and reiterates the insufficiency of the current iodine supplementation measures.

Iodine Intake Estimated by 24 h Urine Collection in the Italian Adult Population: 2008-2012 Survey.

Monitoring the population iodine status is essential for iodine deficiency eradication. This study assessed the average dietary iodine intake and the iodine status of a random sample of the Italian general adult population. The study population included 2378 adults aged 35-79 years (1229 men and 1149 women) from all 20 Italian regions, participating in the Osservatorio Epidemiologico Cardiovascolare/Health Examination Survey 2008-2012 (OEC/HES), and were examined for iodine intake in the framework of the MINISAL-GIRCSI Programme. Dietary iodine intake was assessed by the measurement of 24 h urinary iodine excretion. The median daily iodine intake of the whole population was lower (96 µg/d, interquartile range 51-165) than the daily adequate iodine intake according to both EFSA and WHO recommendation (150 µg/d), with a significantly lower value among women (85 µg/d) compared with men (111 µg/d). Iodine intake diminished with age and increased with BMI (body mass index) in male but not in female participants, without achieving the adequate intake in any sex, age, or BMI category. In this random sample of Italian general adult population examined in 2008-2012, iodine intake still remained lower than the recommended values despite the implementation of a strategy of iodoprophylaxis based on salt iodization in 2005. These data represent a valuable reference for future monitoring of iodine status in our country.

Prenatal and Postpartum Maternal Iodide Intake from Diet and Supplements, Urinary Iodine and Thyroid Hormone Concentrations in a Region of the United Kingdom with Mild-to-Moderate Iodine Deficiency.

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. Iodine requirements increase in pregnancy, but many women in regions without salt iodization have insufficient intakes. We explored associations between iodide intake and urinary iodine concentration (UIC), urinary iodine/creatinine ratio (I/Cr), thyroid stimulating hormone, thyroglobulin, free triiodothyronine, free thyroxine and palpable goiter in a region of mild-to-moderate iodine insufficiency. A total of 246 pregnant women aged 18-40 in Bradford, UK, joined the Health and Iodine in Babies (Hiba) study. They provided detailed information on diet and supplement use, urine and serum samples and were assessed for goiter at around 12, 26 and 36 weeks' gestation, and 6, 18 and 30 weeks postpartum. Dietary iodide intake from food and drink was estimated using six 24 h recalls. During pregnancy, median (IQR) dietary iodide intake was 101 µg/day (54, 142), with 42% from dairy and 9% from white fish. Including supplements, intake was 143 µg/day (94, 196), with 49% < UK reference nutrient intake (140 µg/day). Women with Pakistani heritage had 129 µg/day (87, 190) median total intake. Total intake during pregnancy was associated with 4% (95% CI: 1%, 7%) higher UIC, 5% (3%, 7%) higher I/Cr, 4% (2%, 6%) lower thyroglobulin and 21% (9%, 32%) lower odds of palpable goiter per 50 µg/day. This cohort consumed less iodide in pregnancy than UK and World Health Organization dietary recommendations. UIC, I/Cr and thyroglobulin were associated with intake. Higher intake was associated with fewer goiters. Because dairy was the dominant source of iodide, women following plant-based or low-dairy diets may be at particular risk of iodine insufficiency.

Urinary Iodine Concentrations in Pregnant Women and Offspring Brain Morphology.

Background: Severe maternal iodine deficiency during pregnancy leads to marked intellectual disability in the offspring. Although recent studies showed that even mild-to-moderate maternal iodine deficiency is associated with lower intelligence quotient and attention deficit hyperactivity disorder in offspring, the underlying neurobiological mechanism of these associations remains unknown. The aim of this study was to investigate the association of maternal iodine excretion during pregnancy with offspring brain morphology during pre-adolescence. Methods: This study was embedded within Generation R, a prospective population-based birth cohort in Rotterdam, the Netherlands. We included 990 mother-child pairs with data on urinary iodine concentration (UIC) and creatinine during pregnancy. The UIC was assessed at <18 and/or 18-25 weeks of gestation and offspring brain imaging data were acquired with magnetic resonance imaging (MRI) at age 10 years. We used linear regression to study the association of the iodine-to-creatinine ratio (UI/Creat) with offspring brain MRI outcomes. Results: Maternal UI/Creat during pregnancy was not consistently associated with offspring brain morphology. A low UI/Creat (<150 µg/g) during pregnancy was nominally associated with smaller total gray matter volume, but this did not survive correction for multiple testing. Also, we could not identify a linear association between continuous iodine excretion and offspring brain morphology. Instead, our results suggest a curvilinear association between UI/Creat and brain morphology. In sensitivity analyses using the World Health Organization categorization for UIC values, both low and high UI/Creat were associated with smaller total gray matter volume. Conclusions: The current study provides some but no conclusive evidence for an association of maternal iodine excretion during pregnancy with offspring brain morphology. Our results suggest that the exact definition of the reference group is important because of potential non-linear associations, which could be leveraged in future studies.

Prevalence of inadequate and excessive iodine intake in a US pregnancy cohort.

BACKGROUND: US iodine intake, estimated from the median urinary iodine concentration of population representative data, has declined by half since the 1970s, which is problematic because maternal iodine intake is critical for fetal neurodevelopment. Relying on median urinary concentrations to assess iodine intake of populations is standard practice but does not describe the number of individuals with insufficient intake. Prevalence estimates of inadequate and excessive intake are better for informing public health applications but require multiple urine samples per person; such estimates have been generated in pediatric populations but not yet among pregnant women. OBJECTIVE: Our aims were as follows: (1) to assess median urinary iodine concentrations across pregnancy for comparison with national data and (2) to estimate the prevalence of inadequate and excessive iodine intake among pregnant women in mid-Michigan. STUDY DESIGN: Data were collected from 2008 to 2015 as part of a prospective pregnancy cohort in which women were enrolled at their first prenatal clinic visit. Few exclusion criteria (<18 years or non-English speaking) resulted in a sample of women generally representative of the local community, unselected for any specific health conditions. Urine specimens were obtained as close as practicable to at least 1 specimen per trimester during routine prenatal care throughout pregnancy (n=1-6 specimens per woman) and stored at -80°C until urinary iodine was measured to estimate the iodine intake (n=1014 specimens from 464 women). We assessed urinary iodine across pregnancy by each gestational week of pregnancy and by trimester. We used multiple urine specimens per woman, accounted for within-person variability, performed data transformation to approximate normality, and estimated the prevalence of inadequate and excessive iodine intake using a method commonly employed for assessment of nutrient status. RESULTS: Maternal characteristics reflected the local population in racial and ethnic diversity and socioeconomic status as follows: 53% non-Hispanic white, 22% non-Hispanic black, and 16% Hispanic; 48% had less than or equal to high school education and 71% had an annual income of <$25,000. Median urinary iodine concentrations in the first, second, and third trimester-including some women contributing more than 1 specimen per trimester-were 171 µg/L (n=305 specimens), 181 µg/L (n=366 specimens), and 179 µg/L (n=343 specimens), respectively, with no significant difference by trimester (P=.50, Kruskal-Wallis test for equality of medians). The estimated prevalence of inadequate and excessive iodine intake was 23% and <1%, respectively. CONCLUSION: Median urinary iodine concentrations in each trimester were above the World Health Organization cutoff of 150 µg/L, indicating iodine sufficiency at the group level across pregnancy. However, the estimated prevalence of inadequate iodine intake was substantial at 23%, whereas prevalence of excessive intake was <1%, indicating a need for at least some women to increase consumption of iodine during pregnancy. The American Thyroid Association, the Endocrine Society, and the American Academy of Pediatrics recommend that all pregnant and lactating women receive a daily multivitamin or mineral supplement that contains 150 µg of iodine. The data presented here should encourage the collection of similar data from additional US population samples for the purpose of informing the American College of Obstetricians and Gynecologists' own potential recommendations for prenatal iodine supplementation.

Optimal Assessment and Quantification of Iodine Nutrition in Pregnancy and Lactation: Laboratory and Clinical Methods, Controversies and Future Directions.

Iodine intake must be boosted during pregnancy to meet the demands for increased production and placental transfer of thyroid hormone essential for optimal foetal development. Failure to meet this challenge results in irreversible brain damage, manifested in severity from neurological cretinism to minor or subtle deficits of intelligence and behavioural disorders. Attention is now being focused on explaining observational studies of an association between insufficient iodine intake during pregnancy and mild degrees of intellectual impairment in the offspring and confirming a cause and effect relationship with impaired maternal thyroid function. The current qualitative categorisation of iodine deficiency into mild, moderate and severe by the measurement of the median urinary iodine concentration (MUIC) in a population of school-age children, as a proxy measure of dietary iodine intake, is inappropriate for defining the degree or severity of gestational iodine deficiency and needs to be replaced. This review examines progress in analytical techniques for the measurement of urinary iodine concentration and the application of this technology to epidemiological studies of iodine deficiency with a focus on gestational iodine deficiency. We recommend that more precise definitions and measurements of gestational iodine deficiency, beyond a spot UIC, need to be developed. We review the evidence for hypothyroxinaemia as the cause of intrauterine foetal brain damage in gestational iodine deficiency and discuss the many unanswered questions, from which we propose that further clinical studies need to be designed to address the pathogenesis of neurodevelopmental impairments in the foetus and infant. Agreement on the testing instruments and standardization of processes and procedures for Intelligence Quotient (IQ) and psychomotor tests needs to be reached by investigators, so that valid comparisons can be made among studies of gestational iodine deficiency and neurocognitive outcomes. Finally, the timing, safety and the efficacy of prophylactic iodine supplementation for pregnant and lactating women needs to be established and confirmation that excess intake of iodine during pregnancy is to be avoided.

Maternal Iodine Status is Associated with Offspring Language Skills in Infancy and Toddlerhood.

Inadequate iodine status affects the synthesis of the thyroid hormones and may impair brain development in fetal life. The aim of this study was to explore the association between maternal iodine status in pregnancy measured by urinary iodine concentration (UIC) and child neurodevelopment at age 6, 12 and 18 months in a population-based cohort. In total, 1036 families from nine locations in Norway were enrolled in the little in Norway cohort. The present study includes n = 851 mother-child pairs with singleton pregnancies, no use of thyroid medication in pregnancy, no severe genetic disorder, data on exposure (UIC) in pregnancy and developmental outcomes (Bayley Scales of Infant and Toddler Development, third edition). Data collection also included general information from questionnaires. We examined associations between UIC (and use of iodine-containing supplements) and repeated measures of developmental outcomes using multivariable mixed models. The median UIC in pregnancy was 78 µg/L (IQR 46⁻130), classified as insufficient iodine intake according to the WHO. Eighteen percent reported use of iodine-containing multisupplements. A UIC below ~100 was associated with reduced receptive (p = 0.025) and expressive language skills (p = 0.002), but not with reduced cognitive or fine- and gross motor skills. Maternal use of iodine-containing supplements was associated with lower gross motor skills (b = -0.18, 95% CI = -0.33, -0.03, p = 0.02), but not with the other outcome measures. In conclusion, an insufficient iodine intake in pregnancy, reflected in a UIC below ~100 µg/L, was associated with lower infant language skills up to 18 months. The use of iodine-containing supplements was not associated with beneficial effects.

Is iodine nutrition in the Spanish pediatric population adequate? Historical review and current situation. / ¿Es suficiente la nutrición de yodo en la población infantil española? Revisión histórica y situación actual.

Iodine is an essential component of thyroid hormones, and iodine deficit is the leading cause of preventable mental retardation worldwide. Spain was considered iodine-deficient until 2003. Although iodine urinary levels have been in the optimal range in Spain since 2004, the WHO recognizes that our country does not meet the necessary requirements to ensure that the whole population is not at risk of an iodine deficiency disorder. The aim of this article is to review the current iodine status in Spain. Data from several studies emphasize the low consumption of iodized salt at home. Despite the progress made in recent decades, Spanish children are not exempt from suffering an iodine deficiency disorder. Policies that allow for controlling iodine nutrition and promote universal consumption of iodized salt should therefore be implemented.

Iodine Deficiency in a Study Population of Norwegian Pregnant Women-Results from the Little in Norway Study (LiN).

Iodine sufficiency is particularly important in pregnancy, where median urinary iodine concentration (UIC) in the range of 150⁻250 µg/L indicates adequate iodine status. The aims of this study were to determine UIC and assess if dietary and maternal characteristics influence the iodine status in pregnant Norwegian women. The study comprises a cross-sectional population-based prospective cohort of pregnant women (Little in Norway (LiN)). Median UIC in 954 urine samples was 85 µg/L and 78.4% of the samples (n = 748) were ≤150 µg/L. 23.2% (n = 221) of the samples were ≤50 µg/L and 5.2% (n = 50) were above the requirements of iodine intake (>250 µg/L). Frequent iodine-supplement users (n = 144) had significantly higher UIC (120 µg/L) than non-frequent users (75 µg/L). Frequent milk and dairy product consumers (4⁻9 portions/day) had significantly higher UIC (99 µg/L) than women consuming 0⁻1 portion/day (57 µg/L) or 2⁻3 portions/day (83 µg/L). Women living in mid-Norway (n = 255) had lowest UIC (72 µg/L). In conclusion, this study shows that the diet of the pregnant women did not necessarily secure a sufficient iodine intake. There is an urgent need for public health strategies to secure adequate iodine nutrition among pregnant women in Norway.

Universal Salt Iodization Provides Sufficient Dietary Iodine to Achieve Adequate Iodine Nutrition during the First 1000 Days: A Cross-Sectional Multicenter Study.

Background: Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d. Objective: We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups. Methods: We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk. Results: The salt iodine concentration was low (<15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (>40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia. Conclusions: Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

Suboptimal Iodine Status among Pregnant Women in the Oslo Area, Norway.

Norway has been considered iodine replete for decades; however, recent studies indicate reemergence of inadequate iodine status in different population groups. We assessed iodine status in pregnant women based on urinary iodine concentration (UIC), urinary iodine excretion (UIE), and iodine intake from food and supplements. In 804 pregnant women, 24-h iodine intakes from iodine-rich foods and iodine-containing supplements were calculated. In 777 women, iodine concentration was measured in spot urine samples by inductively coupled plasma/mass spectrometry (ICP-MS). In addition, 49 of the women collected a 24-h urine sample for assessment of UIE and iodine intake from food frequency questionnaire (FFQ). Median UIC was 92 µg/L. Fifty-five percent had a calculated iodine intake below estimated average requirement (EAR) (160 µg/day). Iodine intake from food alone did not provide the amount of iodine required to meet maternal and fetal needs during pregnancy. In multiple regression models, hypothyroidism, supplemental iodine and maternal age were positively associated with UIC, while gestational age and smoking were negatively associated, explaining 11% of the variance. This study clearly shows that pregnant women in the Oslo area are mild to moderate iodine deficient and public health strategies are needed to improve and secure adequate iodine status.

Iodine Status among Somali Immigrants in Norway.

We lack knowledge about iodine status in the Norwegian population in general, and particularly among immigrants. We aimed to estimate the iodine status and potentially associated factors in a Somali population in Norway. Somali men and women aged 20-73, who were living in one district in Oslo, were recruited between December 2015 and October 2016. Twenty-four-hour urine was collected from 169 participants (91 females and 78 males). Iodine was analysed using the Sandell-Kolthoff reaction on microplates and colorimetric measurement. Information about diet was collected using a short food frequency questionnaire. Iodine intake was calculated from the 24-h iodine excretion. The mean urine volume over 24-h was 1.93 liters (min-max: 0.55-4.0) and the urinary iodine concentration (UIC) varied from 13 to 263 µg/L with a median value of 62.5 µg/L indicating a population with mild iodine deficiency. The median daily iodine intake for the study population was estimated to be 124 µg/day. Mean serum thyroid-stimulating hormone, thyroxine (T4) and triiodothyronine (T3) was 2.1 (SD 1.1) mU/L, 15.0 (SD 2.1) pmol/L, and 5.1 (SD 0.6) pmol/L, respectively. No food groups were associated with iodine intake and neither was gender, age, education level nor length of residence in Norway. In conclusion, this study showed that iodine intake was low, and a considerable proportion of the Somali population studied had sub-optimal iodine status. Monitoring of iodine status should be prioritised and measures to ensure adequate iodine intake, particularly among vulnerable groups initiated.

Pre-analytical Factors Influence Accuracy of Urine Spot Iodine Assessment in Epidemiological Surveys.

Urinary iodine concentration (UIC) is commonly used to assess iodine status of subjects in epidemiological surveys. As pre-analytical factors are an important source of measurement error and studies about this phase are scarce, our objective was to assess the influence of urine sampling conditions on UIC, i.e., whether the child ate breakfast or not, urine void rank of the day, and time span between last meal and urine collection. A nationwide, two-stage, stratified, cross-sectional study including 1560 children (6-12 years) was performed in 2012. UIC was determined by the Sandell-Kolthoff method. Pre-analytical factors were assessed from children's mothers by using a questionnaire. Association between iodine status and pre-analytical factors were adjusted for one another and socio-economic characteristics by multivariate linear and multinomial regression models (RPR: relative prevalence ratios). Skipping breakfast prior to morning urine sampling decreased UIC by 40 to 50 µg/L and the proportion of UIC < 100 µg/L was higher among children having those skipped breakfast (RPR = 3.2[1.0-10.4]). In unadjusted analyses, UIC was less among children sampled more than 5 h from their last meal. UIC decreased with rank of urine void (e.g., first vs. second, P < 0.001); also, the proportion of UIC < 100 µg/L was greater among 4th rank samples (vs. second RPR = 2.1[1.1-4.0]). Subjects' breakfast status and urine void rank should be accounted for when assessing iodine status. Providing recommendations to standardize pre-analytical factors is a key step toward improving accuracy and comparability of survey results for assessing iodine status from spot urine samples. These recommendations have to be evaluated by future research.

Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.

PURPOSE: Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 µg/L] and extremely excessive (UIC ≥ 2500 µg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. METHODS: UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with PTC was 287 µg/L (range from 7 to 7, 426 µg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 µg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 µg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 µg/L) and more than excessive (UIC ≥ 500 µg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 µg/L UIC group. CONCLUSION: Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.

Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply.

Pregnant women are prone to iodine deficiency due to the increased need for iodine during gestation. Progress has recently occurred in establishing serum thyroglobulin (Tg) as an iodine status biomarker, but there is no accepted reference range for iodine sufficiency during pregnancy. An observational study was conducted in 164 pregnant women. At week 16 of gestation urinary iodine concentration (UIC), serum Tg, and thyroid functions were measured, and information on the type of iodine supplementation and smoking were recorded. The parameters of those who started iodine supplementation (≥150 µg/day) at least 4 weeks before pregnancy (n = 27), who started at the detection of pregnancy (n = 51), and who had no iodine supplementation (n = 74) were compared. Sufficient iodine supply was found in the studied population based on median UIC (162 µg/L). Iodine supplementation ≥150 µg/day resulted in higher median UIC regardless of its duration (nonusers: 130 µg/L vs. prepregnancy iodine starters: 240 µg/L, and pregnancy iodine starters: 205 µg/L, p < .001, and p = .023, respectively). Median Tg value of pregnancy starters was identical to that of nonusers (14.5 vs. 14.6 µg/L), whereas prepregnancy starters had lower median Tg (9.1 µg/L, p = .018). Serum Tg concentration at week 16 of pregnancy showed negative relationship (p = .010) with duration of iodine supplementation and positive relationship (p = .008) with smoking, a known interfering factor of iodine metabolism, by multiple regression analysis. Serum Tg at week 16 of pregnancy may be a promising biomarker of preconceptual and first trimester maternal iodine status, the critical early phase of foetal brain development.

Age-specific reference interval of serum TSH levels is high in adolescence in an iodine excess area: Korea national health and nutrition examination survey data.

PURPOSE: Serum thyroid-stimulating hormone level was influenced by several factors, including age, gender, thyroid auto-antibodies, race, and intake of dietary iodine. We evaluated age-specific reference interval of serum thyroid-stimulating hormone levels in Korea, an iodine excess area. METHODS: This nationwide population-based cross-sectional study included representative civilian, non-institutional population (n = 6564) who underwent thyroid function tests from Korea National Health and Nutrition Examination Survey VI (2013-2015). The reference interval of serum thyroid-stimulating hormone levels was defined between the 2.5th and 97.5th percentiles in the reference population. RESULTS: The geometric mean of serum thyroid-stimulating hormone levels in the reference population was 2.17 mIU/L with a reference interval of 0.62-6.84 mIU/L. In the reference population, the geometric mean of serum TSH levels in each age group of 10-18, 19-29, 30-39, 40-49, 50-59, 60-69, and equal or older than 70 years was 2.47, 2.20, 2.07, 2.04, 2.23, 2.12, and 2.27 mIU/L, with a reference interval of 0.74-7.35, 0.67-6.42, 0.63-6.04, 0.62-6.20, 0.56-7.37, 0.57-6.90, and 0.42-6.58 mIU/L, respectively. In the reference population, the urinary iodine concentrations were consistently high in all age groups (median 298.5 µg/L). Subjects aged 10-18 years had the highest urinary iodine concentrations. CONCLUSIONS: There was no shift toward higher levels with age in the distribution of serum thyroid-stimulating hormone levels. The reference interval of serum thyroid-stimulating hormone levels was consistently high in all age group, especially from adolescence 10-18 years in a Korean population who had excessive intake of dietary iodine.

Is low iodine a risk factor for cardiovascular disease in Americans without thyroid dysfunction? Findings from NHANES.

BACKGROUND AND AIMS: Low body iodine levels are associated with cardiovascular disease, in part through alterations in thyroid function. While this association suggested from animal studies, it lacks supportive evidence in humans. This study examined the association between urine iodine levels and presence of coronary artery disease (CAD) and stroke in adults without thyroid dysfunction. METHODS AND RESULTS: This cross-sectional study included 2440 adults (representing a weighted n = 91,713,183) aged ≥40 years without thyroid dysfunction in the nationally-representative 2007-2012 National Health and Nutrition Examination Survey. The age and sex-adjusted urine iodine/creatinine ratio (aICR) was categorized into low (aICR<116 µg/day), medium (116 µg/day ≤ aICR < 370µg/day), and high (aICR ≥ 370µg/day) based on lowest/highest quintiles. Stroke and CAD were from self-reported physician diagnoses. We examined the association between low urine aICR and CAD or stroke using multivariable logistic regression modeling. The mean age of this population was 56.0 years, 47% were women, and three quarters were non-Hispanic whites. Compared with high urine iodine levels, multivariable adjusted odds ratios aOR (95% confidence intervals) for CAD were statistically significant for low, aOR = 1.97 (1.08-3.59), but not medium, aOR = 1.26 (0.75-2.13) urine iodine levels. There was no association between stroke and low, aOR = 1.12 (0.52-2.44) or medium, aOR = 1.48 (0.88-2.48) urine iodine levels. CONCLUSION: The association between low urine iodine levels and CAD should be confirmed in a prospective study with serial measures of urine iodine. If low iodine levels precede CAD, then this potential and modifiable new CAD risk factor might have therapeutic implications.

First Israeli National Iodine Survey Demonstrates Iodine Deficiency Among School-Aged Children and Pregnant Women.

BACKGROUND: National data on iodine status in Israel are lacking. Reliance on iodine-depleted desalinated water, the absence of a salt iodization program, and reports of increased use of thyroid medication in Israel suggest that the population's iodine intake is likely inadequate. The aims of this study were therefore to determine the iodine status of Israeli school-age children (SAC) and pregnant women (PW) in a nationally representative sample obtained by a novel approach of using pre-discard urinalysis samples collected from a centralized national laboratory. METHODS: Spot urine samples from 1023 SAC and 1074 PW, representing all regions and major sectors in Israel, were collected during 2016 at the Maccabi Healthcare Services central laboratory. Urinary iodine concentration (UIC) was measured, and the results were analyzed by trimester, sex, region, and sector. RESULTS: SAC were iodine deficient, with a median (interquartile range [IQR]) UIC of 83 µg/L (52-127 µg/L); 62% of SAC UICs were below the World Health Organization adequacy range for SAC (100-199 µg/L). PW were also iodine deficient, with a median (IQR) UIC of 61 µg/L (36-97 µg/L); 85% of PW UICs were below the adequacy range for PW (150-249 µg/L). For both SAC and PW, the median UIC was below the World Health Organization's adequacy range across all sectors, sexes, and districts. Among SAC, the median (IQR) UIC was lower among females (75 µg/L; 48-119 µg/L) than males (92 µg/L; 59-133 µg/L; p < 0.05). Median UIC values of PW correlated significantly with the median UIC for SAC by sub-district (R2 = 0.3, p < 0.05). CONCLUSIONS: Urine sampling via a centralized national laboratory was efficient and cost-saving. Iodine deficiency in Israeli SAC and PW is a serious public-health concern. A national program of salt iodization and iodine supplementation of PW should be urgently considered.

Thyroid homeostasis in mother-child pairs in relation to maternal iodine status: the MISA study.

BACKGROUND/OBJECTIVES: Iodine deficiency during pregnancy may influence maternal and foetal thyroid function with the risk of causing neurocognitive and psychomotor deficits in the offspring. The objective of this study was to assess iodine status in pregnant women from Northern Norway and to investigate the influence of iodine status on maternal and infant thyroid function. SUBJECTS/METHODS: Women from the Northern Norway Mother-and-Child contaminant Cohort Study (MISA) donated a blood and urine sample at three visits during their pregnancy and postpartum period (in second trimester, 3 days and 6 weeks after delivery. N=197). Women were assigned to iodine status groups according to urine iodine concentrations (UICs) in second trimester and mixed effects linear models were used to investigate potential associations between iodine status and repeated measurements of thyroid-stimulating hormone (TSH), thyroid hormones (THs), TH-binding proteins and thyroid peroxidase antibodies. Associations between maternal iodine status and TSH in heel prick samples from the infants were investigated with linear regression. RESULTS: Median UIC in second trimester was 84 µg/l (range 18-522) and 80% had UIC below recommended level (<150 µg/l). Iodine-deficient women had higher concentrations of T3, FT3 and FT4 (estimated differences (confidence intervals) of 0.10 nmol/l (0.01, 0.17), 0.16 pmol/l (0.05, 0.26) and 0.45 pmol/l (0.10, 0.78), respectively) compared with iodine-sufficient women. The concentrations varied within normal reference ranges, but the majority of women with subclinical hypothyroidism were iodine deficient. Maternal iodine status did not influence infant TSH concentrations. CONCLUSIONS: This study indicate iodine deficiency among pregnant women in Norway. Iodine status during pregnancy influences maternal thyroid homeostasis and is therefore a risk factor for foetal and infant development.

Reliability of thyroglobulin in serum compared with urinary iodine when assessing individual and population iodine nutrition status.

The occurrence of thyroid disorders relies on I nutrition and monitoring of all populations is recommended. Measuring I in urine is standard but thyroglobulin in serum is an alternative. This led us to assess the reliability of studies using serum thyroglobulin compared with urinary I to assess the I nutrition level and calculate the number of participants needed in a study with repeated data sampling in the same individuals for 1 year. Diet, supplement use and life style factors were assessed by questionnaires. We measured thyroglobulin and thyroglobulin antibodies in serum and I in urine. Participants were thirty-three Caucasians and sixty-four Inuit living in Greenland aged 30-49 years. Serum thyroglobulin decreased with rising I excretion (Kendall's τ -0·29, P=0·005) and did not differ with ethnicity. Variation in individuals was lower for serum-thyroglobulin than for urinary I (mean individual CV: 15·1 v. 46·1 %; P<0·01). It required 245 urine samples to be 95 % certain of having a urinary I excretion within 10 % of the true mean of the population. For serum-thyroglobulin the same precision required 206 samples. In an individual ten times more samples were needed to depict I deficiency when using urinary I excretion compared with serum-thyroglobulin. In conclusion, more participants are need to portray I deficiency in a population when using urinary I compared with serum-thyroglobulin, and about ten times more samples are needed in an individual. Adding serum-thyroglobulin to urinary I may inform surveys of I nutrition by allowing subgroup analysis with similar reliability.