Iodine contrast exposure and incident COVID-19 infection.

Background: Iodine and particularly its oxidated forms have long been recognized for its effective antiseptic properties. Limited in vitro and in vivo data suggest that iodine exposure may rapidly inactivate, reduce transmission, and reduce infectivity of SARS-CoV-2. We hypothesized that iodine exposure may be associated with decreased incident COVID-19 infection. Methods: A retrospective population-level cohort analysis was performed of the U.S. Veterans Health Administration between 1 March 2020 and 31 December 2020, before the widespread availability of vaccines against SARS-CoV-2. Multivariable logistic regression models estimated the adjusted odds ratios (OR) and 95% confidence intervals (CI) of the associations between iodinated contrast exposure and incident COVID-19 infection, adjusting for age, sex, race/ethnicity, place of residence, socioeconomic status, and insurance status. Results: 530,942 COVID-19 tests from 333,841 Veterans (mean ± SD age, 62.7 ± 15.2 years; 90.2% men; 61.9% non-Hispanic Whites) were analyzed, of whom 9% had received iodinated contrast ≤60 days of a COVID-19 test. Iodine exposure was associated with decreased incident COVID-19 test positivity (OR, 0.75 95% CI, 0.71-0.78). In stratified analyses, the associations between iodinated contrast use and decreased COVID-19 infection risk did not differ by age, sex, and race/ethnicity. Conclusion: Iodine exposure may be protective against incident COVID-19 infection. Weighed against the risks of supraphysiologic iodine intake, dietary, and supplemental iodine nutrition not to exceed its Tolerable Upper Limit may confer an antimicrobial benefit against SARS-CoV-2. A safe but antimicrobial level of iodine supplementation may be considered in susceptible individuals, particularly in geographic regions where effective COVID-19 vaccines are not yet readily available.

Excess iodine exposure acutely increases salivary iodide and antimicrobial hypoiodous acid concentrations in humans.

The lactoperoxidase (LPO)-hydrogen peroxide-halides reaction (LPO system) converts iodide and thiocyanate (SCN-) into hypoiodous acid (HOI) and hypothiocyanite (OSCN-), respectively. Since this system has been implicated in defense of the airways and oropharynx from microbial invasion, in this proof-of-concept study we measured the concentrations of these analytes in human saliva from a convenience clinical sample of 40 qualifying subjects before and after acute iodine administration via the iodinated contrast medium used in coronary angiography to test the hypothesis that an iodide load increases salivary iodide and HOI concentrations. Saliva was collected and salivary iodide, SCN-, HOI and OSCN- were measured using standard methodology. The large iodine load delivered by the angiographic dye, several 100-fold in excess of the U.S. Recommended Daily Allowance for iodine (150 µg/day), significantly increased salivary iodide and HOI levels compared with baseline levels, whereas there was no significant change in salivary SCN- and OSCN- levels. Iodine load and changes of salivary iodide and HOI levels were positively correlated, suggesting that higher iodide in the circulation increases iodide output and salivary HOI production. This first of its kind study suggests that a sufficient but safe iodide supplementation less than the Tolerable Upper Limit for iodine set by the U.S. Institute of Medicine (1,100 µg/day) may augment the generation of antimicrobial HOI by the salivary LPO system in concentrations sufficient to at least in theory protect the host against susceptible airborne microbial pathogens, including enveloped viruses such as coronaviruses and influenza viruses.

Iodine Nutrition in Weaning Infants in the United States.

BACKGROUND: As iodine is a requisite micronutrient for infant brain development, infants are at risk for iodine deficiency during the weaning period when their diet transitions from milk (breast-milk, infant formula, or follow-on formula) to solid food. Dietary iodine intake during this weaning period is likely minimal, as the iodine content of commercial baby food is not regulated, and the addition of salt to baby food is not recommended. This study reports the current status of iodine nutrition among weaning infants in the United States. METHODS: Subjects (n = 60; 50% Caucasian, 30% black) were infants <12 months of age who were fed any combination of formula and/or baby food. Samples of all formula and food consumed in the previous 24 hours and a spot urine sample from each infant were obtained for the measurement of iodine. The estimated quantities of ingested formula and baby food were summed from a food diary recorded by the infants' parents. RESULTS: The mean age of the infants was 6.3 ± 3.5 months. The median urinary iodine concentration (UIC) was 117 µg/L (range 26.9-1302.8 µg/L). Estimated daily iodine intake obtained from the measured iodine content in infant formula/foods was 89 µg (range 0-288 µg). There was a positive correlation between the infants' UIC and the iodine content in the consumed foods (r = 0.4, p < 0.001). CONCLUSIONS: Although the median UIC of infants fed a combination of infant formula and baby food would meet the criteria for iodine sufficiency in a larger sample, those consuming the lowest quartile of iodine-containing nutritional sources had a median UIC <100 µg/L.

Concurrent Milk Ingestion Decreases Absorption of Levothyroxine.

BACKGROUND: Levothyroxine is the most commonly prescribed medication in the United States. Many foods and medications, including calcium supplements, can interfere with levothyroxine absorption. No studies have investigated the effect of cow's milk, a common breakfast staple, on the absorption of oral levothyroxine. Cow's milk contains approximately 450 mg of elemental calcium per 12 oz (355 mL) serving. METHODS: A pharmacokinetic study was conducted in healthy euthyroid subjects to assess levothyroxine absorption with and without concurrent cow's milk consumption. Following an overnight fast, serum total thyroxine (TT4) concentrations were measured at baseline and at one, two, four, and six hours after ingestion of 1000 µg of oral levothyroxine alone or when co-administered with 12 oz (355 mL) of 2% milk. There was a four-week washout period between the two assessments in each subject. RESULTS: Ten subjects (Mage ± SD = 33.7 ± 10.2 years; 60% male) completed the study. The area under the curve (AUC) of TT4 concentrations was significantly lower when levothyroxine was ingested along with 12 oz (355 mL) of 2% cow's milk (M ± SD = 67.3 ± 12.1) compared to that with levothyroxine alone (73.5 ± 17.0; p = 0.02). Also, peak serum TT4 concentrations were significantly lower when cow's milk was co-administered with levothyroxine (M ± SD = 14.1 ± 0.8 µg/dL) than with levothyroxine alone (13.0 ± 0.9 µg/dL; p = 0.04). CONCLUSIONS: This is the first study to demonstrate that concurrent cow's milk ingestion reduces oral levothyroxine absorption. The findings support previous literature showing the interference of elemental calcium and food with thyroid hormone absorption. Patients managed with thyroid hormone should be advised to avoid taking their levothyroxine simultaneously with cow's milk.

Urinary Iodine, Perchlorate, and Thiocyanate Concentrations in U.S. Lactating Women.

BACKGROUND: Iodine is an essential micronutrient for thyroid hormone production. Adequate iodine intake and normal thyroid function are important during early development, and breastfed infants rely on maternal iodine excreted in breast milk for their iodine nutrition. The proportion of women in the United States of childbearing age with urinary iodine concentration (UIC) <50 µg/L has been increasing, and a subset of lactating women may have inadequate iodine intake. UIC may also be influenced by environmental exposure to perchlorate and thiocyanate, competitive inhibitors of iodine transport into thyroid, and lactating mammary glands. Data regarding UIC in U.S. lactating women are limited. To adequately assess the iodine sufficiency of lactating women and potential associations with environmental perchlorate and thiocyanate exposure, we conducted a multicenter, cross-sectional study of urinary iodine, perchlorate, and thiocyanate concentrations in healthy U.S. lactating women. METHODS: Lactating women ≥18 years of age were recruited from three U.S. geographic regions: California, Massachusetts, and Ohio/Illinois from November 2008 to June 2016. Demographic information and multivitamin supplements use were obtained. Iodine, perchlorate, and thiocyanate levels were measured from spot urine samples. Correlations between urinary iodine, perchlorate, and thiocyanate levels were determined using Spearman's rank correlation. Multivariable regression models were used to assess predictors of urinary iodine, perchlorate, and thiocyanate levels, and UIC <100 µg/L. RESULTS: A total of 376 subjects (≥125 from each geographic region) were included in the final analyses [mean (SD) age 31.1 (5.6) years, 37% white, 31% black, and 11% Hispanic]. Seventy-seven percent used multivitamin supplements, 5% reported active cigarette smoking, and 45% were exclusively breastfeeding. Median urinary iodine, perchlorate, and thiocyanate concentrations were 143 µg/L, 3.1 µg/L, and 514 µg/L, respectively. One-third of women had UIC <100 µg/L. Spot urinary iodine, perchlorate, and thiocyanate levels all significantly positively correlated to each other. No significant predictors of UIC, UIC <100 µg/L, or urinary perchlorate levels were identified. Smoking, race/ethnicity, and marital status were significant predictors of urinary thiocyanate levels. CONCLUSION: Lactating women in three U.S. geographic regions are iodine sufficient with an overall median UIC of 143 µg/L. Given ubiquitous exposure to perchlorate and thiocyanate, adequate iodine nutrition should be emphasized, along with consideration to decrease these exposures in lactating women to protect developing infants.

HIGH PREVALENCE OF AGENT ORANGE EXPOSURE AMONG THYROID CANCER PATIENTS IN THE NATIONAL VA HEALTHCARE SYSTEM.

OBJECTIVE: Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S. Little is known regarding the epidemiology and characteristics of patients with thyroid cancer within the national Veterans Health Administration (VHA) integrated healthcare system. The aim of this study was to further understand the characteristics of thyroid cancer patients in the VHA population, particularly in relation to Agent Orange exposure. METHODS: This is a descriptive analysis of the VA (Veterans Affairs) Corporate Data Warehouse database from all U.S. VHA healthcare sites from October1, 1999, to December 31, 2013. Information was extracted for all thyroid cancer patients based on International Classification of Diseases-ninth revision diagnosis codes; histologic subtypes of thyroid cancer were not available. RESULTS: There were 19,592 patients (86% men, 76% white, 58% married, 42% Vietnam-era Veteran) in the VHA system with a diagnosis of thyroid cancer within this 14-year study period. The gender-stratified prevalence rates of thyroid cancer among the Veteran population during the study period were 1:1,114 (women) and 1:1,023 (men), which were lower for women but similar for men, when compared to the U.S. general population in 2011 (1:350 for women and 1:1,219 for men). There was a significantly higher proportion of self-reported Agent Orange exposure among thyroid cancer patients (10.0%), compared to the general VHA population (6.2%) (P<.0001). CONCLUSION: Thyroid cancer patients, in this sample, have a higher prevalence of self-reported Agent Orange exposure compared to the overall national VA patient population. ABBREVIATIONS: T4 = thyroxine TCDD = 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin TSH = thyroid-stimulating hormone VA = Veterans Affairs VHA = Veterans Health Administration.

Concentrations of thiocyanate and goitrin in human plasma, their precursor concentrations in brassica vegetables, and associated potential risk for hypothyroidism.

Brassica vegetables are common components of the diet and have beneficial as well as potentially adverse health effects. Following enzymatic breakdown, some glucosinolates in brassica vegetables produce sulforaphane, phenethyl, and indolylic isothiocyanates that possess anticarcinogenic activity. In contrast, progoitrin and indolylic glucosinolates degrade to goitrin and thiocyanate, respectively, and may decrease thyroid hormone production. Radioiodine uptake to the thyroid is inhibited by 194 µmol of goitrin, but not by 77 µmol of goitrin. Collards, Brussels sprouts, and some Russian kale (Brassica napus) contain sufficient goitrin to potentially decrease iodine uptake by the thyroid. However, turnip tops, commercial broccoli, broccoli rabe, and kale belonging to Brassica oleracae contain less than 10 µmol of goitrin per 100-g serving and can be considered of minimal risk. Using sulforaphane plasma levels following glucoraphanin ingestion as a surrogate for thiocyanate plasma concentrations after indole glucosinolate ingestion, the maximum thiocyanate contribution from indole glucosinolate degradation is estimated to be 10 µM, which is significantly lower than background plasma thiocyanate concentrations (40-69 µM). Thiocyanate generated from consumption of indole glucosinolate can be assumed to have minimal adverse risks for thyroid health.

No difference in urinary iodine concentrations between Boston-area breastfed and formula-fed infants.

BACKGROUND: Thyroid hormone is essential for normal mental and physical development in infancy and childhood and is dependent on adequate iodine intake. During the first few months of life, infants are reliant on breastmilk and/or infant formula as their sole sources of dietary iodine. The iodine status of U.S. infants has not been well studied. METHODS: This was a cross-sectional study of 95 breastfed and/or formula-fed infants less than 3 months of age in the Boston area. We measured iodine content from infants' single spot urine samples and assessed associations with infant feeding type as well as maternal demographic data, salt and multivitamin use, smoking status, and diet. RESULTS: The median infant urine iodine concentration was 197.5 µg/L (range 40-897.5 µg/L). Median infant urine iodine concentrations were similar between infants who were exclusively breastfed (n=39, 203.5 µg/L; range 61.5-395.5 µg/L), formula-fed (n=44, 182.5 µg/L; range 40-897.5 µg/L), and mixed (n=10, 197.8 µg/L; range 123-592.5) (p=0.88). There were no significant correlations of infant urinary iodine with maternal salt or multivitamin use (regularly or in the past 24 hours), active or secondhand cigarette smoke exposures, infant weight, infant length, or recent maternal ingestion of common iodine-containing foods, although the correlations with iodine-containing foods are difficult to accurately determine due to the small sample sizes of these variables. CONCLUSIONS: Both breastfed and formula-fed infants less than 3 months of age in the Boston area were generally iodine sufficient. Larger studies are needed to confirm these observations among infants nationwide and elucidate other factors that may contribute to infant iodine nutrition.

Long-term efficacy of modified-release recombinant human thyrotropin augmented radioiodine therapy for benign multinodular goiter: results from a multicenter, international, randomized, placebo-controlled, dose-selection study.

BACKGROUND: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ((131)I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with (131)I therapy. METHODS: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2 ± 9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0 mL; range 31.9-242.2 mL) were randomized to receive placebo (n=32), 0.01 mg MRrhTSH (n=30), or 0.03 mg MRrhTSH (n=33) 24 hours before a calculated (131)I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. RESULTS: At six months, TV reduction was enhanced in the 0.03 mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01 mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44 ± 12.7% (SD) in the placebo group, 41 ± 21.0% in the 0.01 mg MRrhTSH group, and 53 ± 18.6% in the 0.03 mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03 mg MRrhTSH group, the subset of patients with basal (131)I uptake <20% had a 24% greater TV reduction at 36 months than the corresponding subset of patients in the placebo group (p=0.01). At 36 months, the largest relative increase in SCAT was observed in the 0.03 mg MRrhTSH group (13.4 ± 23.2%), but this was not statistically different from the increases observed in the placebo or the 0.01 mg MRrhTSH group (p=0.15). Goiter-related symptoms were reduced and QoL improved, without any enhanced benefit from using MRrhTSH. At three years, the prevalence of permanent hypothyroidism was 13%, 33%, and 45% in the placebo, 0.01 mg, and 0.03 mg MRrhTSH groups respectively. The overall safety profile of the study was favorable. CONCLUSIONS: When used as adjuvant to (131)I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤ 0.03 mg, indicating that the lower threshold for efficacy is around this level.

History of U.S. iodine fortification and supplementation.

Iodine is a micronutrient required for thyroid hormone production. This review highlights the history of the discovery of iodine and its uses, discusses the sources of iodine nutrition, and summarizes the current recommendations for iodine intake with a focus on women of childbearing age.

Iodine-induced thyroid dysfunction.

PURPOSE OF REVIEW: To summarize the mechanisms of iodine-induced hypothyroidism and hyperthyroidism, identify the risk factors for thyroid dysfunction following an iodine load, and summarize the major sources of excess iodine exposure. RECENT FINDINGS: Excess iodine is generally well tolerated, but individuals with underlying thyroid disease or other risk factors may be susceptible to iodine-induced thyroid dysfunction following acute or chronic exposure. Sources of increased iodine exposure include the global public health efforts of iodine supplementation, the escalating use of iodinated contrast radiologic studies, amiodarone administration in vulnerable patients, excess seaweed consumption, and various miscellaneous sources. SUMMARY: Iodine-induced thyroid dysfunction may be subclinical or overt. Recognition of the association between iodine excess and iodine-induced hypothyroidism or hyperthyroidism is important in the differential diagnosis of patients who present without a known cause of thyroid dysfunction.

Iodine nutrition in pregnancy and lactation.

Adequate iodine intake is required for the synthesis of thyroid hormones that are important for normal fetal and infant neurodevelopment. In this review, we discuss iodine physiology during pregnancy and lactation, methods to assess iodine sufficiency, the importance of adequate iodine nutrition, studies of iodine supplementation during pregnancy and lactation, the consequences of hypothyroidism during pregnancy, the current status of iodine nutrition in the United States, the global efforts toward achieving universal iodine sufficiency, and substances that may interfere with iodine use.

Iodine status and thyroid function of Boston-area vegetarians and vegans.

CONTEXT: Adequate dietary iodine is required for normal thyroid function. The iodine status and thyroid function of U.S. vegetarians and vegans have not been previously studied. Environmental perchlorate and thiocyanate (inhibitors of thyroid iodine uptake) exposures may adversely affect thyroid function. OBJECTIVE: The objective of the study was to assess the iodine status and thyroid function of U.S. vegetarians (consume plant based products, eggs, milk; abstain from meat, poultry, fish, shellfish) and vegans (avoid all animal products) and whether these may be affected by environmental perchlorate and thiocyanate exposures. DESIGN AND SETTING: This was a cross-sectional assessment of urinary iodine, perchlorate, and thiocyanate concentrations and serum thyroid function in Boston-area vegetarians and vegans. SUBJECTS: One hundred forty-one subjects (78 vegetarians, 63 vegans) were recruited; one vegan was excluded. RESULTS: Median urinary iodine concentration of vegans (78.5 µg/liter; range 6.8-964.7 µg/liter) was lower than vegetarians (147.0 µg/liter; range 9.3-778.6 µg/liter) (P < 0.01). Adjusted for cigarette smoking (confirmed by urinary cotinine levels) and thiocyanate-rich food consumption, median urinary thiocyanate concentration of vegans (630 µg/liter; range 108-3085 µg/liter) was higher than vegetarians (341 µg/liter; range 31-1963 µg/liter) (P < 0.01). There were no between-group differences in urinary perchlorate concentrations (P = 0.75), TSH (P = 0.46), and free T(4) (P = 0.77). Urinary iodine, perchlorate, and thiocyanate levels were not associated with TSH (P = 0.59) or free T(4) (P = 0.14), even when adjusted for multiple variables. CONCLUSIONS: U.S. vegetarians are iodine sufficient. U.S. vegans may be at risk for low iodine intake, and vegan women of child-bearing age should supplement with 150 µg iodine daily. Environmental perchlorate and thiocyanate exposures are not associated with thyroid dysfunction in these groups.

Colostrum iodine and perchlorate concentrations in Boston-area women: a cross-sectional study.

OBJECTIVE: To measure levels of colostrum iodine, which has not been previously measured, and perchlorate and cotinine (a surrogate for thiocyanate derived from cigarette smoke) in women up to 60 h postpartum. Perchlorate and thiocyanate are environmental inhibitors of iodide transport into the thyroid and lactating breast. DESIGN: Cross-sectional. PATIENTS: Ninety seven postpartum women in Boston, Massachusetts, USA. MEASUREMENTS: Colostrum iodine and perchlorate, and spot urine iodine, perchlorate, cotinine and creatinine concentrations were measured. RESULTS: Sufficient colostrum was obtained to measure iodine in 61 samples and perchlorate in 46 samples. Median colostrum iodine content was 51.4 micromol/l (range 21.3-304.2 microg/l). Perchlorate was detectable in 43 of 46 colostrum samples (median 2.5 micromol/l; range, < 0.05-188.9 micromol/l). Median urine iodine in 97 samples was 82.2 micromol/l (range, 10.3-417.1 micromol/l). Perchlorate was detectable in all 97 urine samples (median 2.6 micromol/l; range, 0.2-160.6 micromol/l). Colostrum iodine content was not significantly correlated with levels of colostrum perchlorate or concentrations per litre of urinary iodine, perchlorate, or cotinine. Colostrum perchlorate concentrations were not significantly associated with urinary iodine, perchlorate, or cotinine levels. Urinary cotinine levels were not significantly associated with urinary iodine or perchlorate levels. There was no association between maternal urinary iodine and urinary perchlorate levels. CONCLUSIONS: Iodine is present in human colostrum and thus available for breastfeeding infants immediately after birth. Perchlorate was also present in 93% of samples measured, but the concentrations did not correlate with colostrum iodine concentrations.

Breast milk iodine and perchlorate concentrations in lactating Boston-area women.

CONTEXT: Breastfed infants rely on adequate maternal dietary iodine intake. OBJECTIVE: Our objective was to measure breast milk iodine and perchlorate, an inhibitor of iodide transport into the thyroid and potentially into breast milk, in Boston-area women. PARTICIPANTS: The study included 57 lactating healthy volunteers in the Boston area. MEASUREMENTS: Breast milk iodine and perchlorate concentrations and urine iodine, perchlorate, and cotinine concentrations were measured. For comparison, iodine and perchlorate levels in infant formulae were also measured. RESULTS: Median breast milk iodine content in 57 samples was 155 microg/liter (range, 2.7-1968 microg/liter). Median urine iodine was 114 microg/liter (range, 25-920 microg/liter). Perchlorate was detectable in all 49 breast milk samples (range, 1.3-411 microg/liter), all 56 urine samples (range, 0.37-127 microg/liter), and all 17 infant formula samples (range, 0.22-4.1 microg/liter) measured. Breast milk iodine content was significantly correlated with urinary iodine per gram creatinine and urinary cotinine but was not significantly correlated with breast milk or urinary perchlorate. CONCLUSIONS: Perchlorate exposure was not significantly correlated with breast milk iodine concentrations. Perchlorate was detectable in infant formula but at lower levels than in breast milk. Forty-seven percent of women sampled may have been providing breast milk with insufficient iodine to meet infants' requirements.