Sam Pino

The Effect of Short-Term Low-Dose Perchlorate on Various Aspects of Thyroid Function

Perchlorate (ClO4) salts are found in rocket fuel, fireworks, and fertilizer. Because of ground water contamination, ClO4 has recently been detected in large public water supplies in several states in the 4-18 microg/L (parts per billion [ppb]) range. The potential adverse effect of chronic low level ClO4 ingestion on thyroid function is of concern to the Environmental Protection Agency (EPA). The daily ingestion of ClO4 at these levels would be magnitudes below the therapeutic effect level of hundreds of milligrams of ClO4 used in treating hyperthyroidism. Studies were carried out in nine healthy male volunteers who had normal thyroid function and negative thyroid antibodies to determine whether the ingestion of 10 mg of ClO4 daily (approximately 300 times the estimated maximum amount of ClO4 consumed from the affected water supplies) would affect any aspect of thyroid function. They ingested 10 mg of ClO4 dissolved in a liter of spring water during waking hours for 14 days. Baseline serum thyrotropin (TSH), free thyroxine index (FTI), total triiodothyronine (TT3), 4-, 8-, and 24-hour thyroid 123I uptakes (RAIU), serum and 24-hour urine ClO4, 24-hour urine iodine, complete blood count (CBC), and chemistry profile were determined. All blood and urine tests were repeated on days 7 and 14 of ClO4 administration and thyroid RAIU on day 14 of ClO4 administration. All tests were repeated 14 days after ClO4 was discontinued. No effect of ClO4 on serum thyroid hormone or TSH concentrations, urinary iodine excretion, CBC, or blood chemistry was observed. Urine and serum ClO4 levels were appropriately elevated during the course of ClO4 ingestion in all subjects, demonstrating compliance. By day 14 of ClO4 administration, the 4-, 8-, and 24-hour thyroid RAIU values decreased in all nine subjects by a mean value of 38% from baseline and rebounded above baseline values by 25% at 14 days after ClO4 withdrawal (p < 0.01 analysis of variance (ANOVA) and Tukey). It is well known that the major effect of ClO4 on the thyroid is a decrease in the thyroid iodide trap by competitive inhibition of the sodium iodide symporter (NIS). The present study demonstrates the sensitivity of the thyroid iodide trap to ClO4 because a low dose of 10 mg daily significantly decreased the thyroid RAIU without affecting circulating thyroid hormone or TSH concentrations. It is possible, however, that the daily consumption of low levels of ClO4 in drinking water over a prolonged period of time could adversely affect thyroid function but no evidence of hypothyroidism was observed at 10 mg of ClO4 daily in this 2-week study. It is now of interest to determine a no effect level for ClO4 on the inhibition of the thyroid RAIU and to carry out a long-term ClO4 exposure study.

Thyroid health status of ammonium perchlorate workers: a cross-sectional occupational health study.

Since pharmaceutical exposures to perchlorate are known to suppress thyroid function in patients with hyperthyroidism, a study of employees at a perchlorate manufacturing plant was conducted to assess whether occupational exposure to perchlorate suppresses thyroid function. Exposure to perchlorate was assessed by measurement of ambient air concentrations of total and respirable perchlorate particles, and systemic absorption was assessed by measurement of urinary perchlorate excretion. Airborne exposures ranged from 0.004 to 167 mg total particulate perchlorate per day. Urinary perchlorate measurements demonstrated that exposure to the airborne particulate perchlorate resulted in systemic absorption. Workers were grouped into four exposure categories with mean absorbed perchlorate dosages of 1, 4, 11 and 34 mg perchlorate per day. Thyroid function was assessed by measurement of serum thyroid-stimulating hormone, free thyroxine index, thyroxine, triiodothyronine, thyroid hormone binding ratio, thyroid peroxidase antibodies, and by clinical examination. No differences in thyroid-function parameters were found between the four groups of workers across approximately three orders of magnitude of exposure and of dose. Thus human thyroid function was not affected by these levels of absorbed perchlorate. In addition, no clinical evidence of thyroid abnormalities was found in any exposure group. The blood-cell counts were normal in all groups, indicating no evidence of hematotoxicity in this exposure range. The absence of evidence of an effect on thyroid function or blood cells from occupational airborne perchlorate exposure at a mean absorption of 34 mg/day demonstrates a no-observed-adverse-effect-level (NOAEL) that can assist in the evaluation of human health risks from environmental perchlorate contamination.

Use of Inductively Coupled Plasma Mass Spectrometry to Measure Urinary Iodine in NHANES 2000: Comparison with Previous Method

Urinary iodine (UI) concentrations directly reflect dietary iodine intake and consequently test biochemical assessment of the iodine status worldwide (1). The Iodine Laboratory of the Division of Laboratory Sciences at the National Center for Environmental Health, CDC, measured the UI content of specimens as part of the National Health and Nutrition Examination Survey (NHANES) 2000 and will measure UI in the US population through future NHANES analyses, using inductively coupled plasma mass spectrometry (ICP-MS). In this report, we describe the ICP-MS laboratory method and compare that method with the established Sandell–Kolthoff (S-K) spectrophotometric method used in NHANES III. The ICP-MS method described previously (2) was modified for use in NHANES 2000 by adding alkaline diluents and rinses to measure UI as follows: urine samples and the urine iodide calibrator solutions were prepared just before analysis by dilution (1:49; 50 μL of sample/calibrator plus 2450 μL of diluent) with an aqueous solution of 10 mL/L tetramethylammonium hydroxide containing 10 μg/L tellurium as an internal standard. A peristaltic pump introduced the diluted samples into the spray chamber with an argon stream. The I+ and Te+ ions were measured at m/z 127 and 130, respectively (3). The diluent used to make the intermediate working calibrators was 1.0 g of analytical-reagent-grade sodium thiosulfate (Na2S2O3) dissolved in 1000 mL of 18 MΩ · cm ultrapure water. (The water used for all dilutions and rinses in the ICP-MS method is ultrapure 18 MΩ · cm water; Millipore Corporation.) The wash solution was an aqueous solution of 1 mL/L Triton X-100 and 10 mL/L tetramethylammonium hydroxide. This solution was …

Congenital Hypothyroidism Caused by Excess Prenatal Maternal Iodine Ingestion

We report the cases of 3 infants with congenital hypothyroidism detected with the use of our newborn screening program, with evidence supporting excess maternal iodine ingestion (12.5 mg/d) as the etiology. Levels of whole blood iodine extracted from their newborn screening specimens were 10 times above mean control levels. Excess iodine ingestion from nutritional supplements is often unrecognized.

Dietary Iodine in Pregnant Women from the Boston, Massachusetts Area

ADEQUATE MATERNAL IODINE intake is essential for fetal neurodevelopment. Worldwide, iodine deficiency is the leading cause of preventable mental retardation (1). Since the iodization of salt and other foods in the 1920s, U.S. dietary iodine has generally been adequate. However the median adult U.S. dietary iodine intake decreased by 50% from the time of the first National Health and Nutrition Examination Survey (NHANES I, 1971–1974) to the time of NHANES III (1988–1994) (2). Women of childbearing age may be at increasing risk for moderate iodine deficiency. The U.S. Institute of Medicine’s recommended dietary allowance (RDA) for pregnant women is 220 mg iodine daily (3); this corresponds approximately to a urinary iodine concentration of 15 mg/dL. The median urinary iodine value in pregnant women (n 5 208) from NHANES I was 32.7 mg/dL, with 1% of the women sampled having urinary iodine levels below 5 mg/dL. The median urinary iodine level among pregnant women from NHANES III (n 5 348) was 14.1 mg/dL, with 6.9% having urinary iodine levels below 5 mg/L. Dietary iodine is currently being surveyed in NHANES IV but results will not be reported until after the survey is completed. We obtained spot urine specimens from a sample of 100 consecutive healthy pregnant women from a Boston, Massachusetts, inner-city obstetric clinic (mean age 29 6 standard deviation [SD] 6.8 years; 6% Asian, 14% Hispanic, 16% white, 49% black, 15% other or undetermined). Women were in the first or second trimester of pregnancy. Total urine iodine concentrations were measured spectrophotometrically by a modification of the method of Benotti et al (4). The study was reviewed by an Institutional Review Board, and informed consent was obtained from all subjects. The median urinary iodine in our sample was 14.9 mg/dL. Urinary iodine levels ranged from 1.3 mg/dL to 120 mg/dL. Nine percent of women sampled had urinary iodine levels below 5 mg/dL (iodine deficiency) and 49% had values below that recommended for pregnant women (Fig. 1). These data suggest that dietary iodine intake in pregnant U.S. women has remained stable over the past decade, and that population dietary iodine levels remain adequate by World Health Organization standards (5). However, approximately half of the pregnant women in our sample had iodine intake below the U.S. RDA, and 9% had levels consistent with iodine deficiency. Although cretinism due to iodine deficiency is not a problem in the United States, subtle THYROID Volume 14, Number 4, 2004

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.

High iodine content of Korean seaweed soup: a health risk for lactating women and their infants?

Iodine requirements increase during pregnancy and lactation due to increased maternal thyroid hormone production and iodine excretion, fetal iodine requirements, and loss of iodine in breast milk. Seaweed preparations are a source of dietary iodine. Korean and many Korean-American women traditionally consume brown seaweed soup (Undaria pinnatifida) daily during the early postpartum period (Supplementary Data; Supplementary Data are available online at www .liebertonline.com/thy) (1). This tradition is maintained among Korean and Korean-American women such that their breast milk iodine correlates strongly with frequency and quantity of seaweed soup consumption (2,3). As the iodine content of this soup has not been reported, we randomly selected 10 brands of dried brown seaweed from Korea and China available in the United States. Seaweed soup from each brand was prepared utilizing the following ingredients: 1 oz of dried seaweed, 6 cups water, 1⁄4 pound beef, 11⁄2 tablespoons soy sauce, 2 teaspoons sesame oil, 1 teaspoon garlic, and *1⁄2 teaspoon noniodized sea salt (Supplementary Data). Iodine content of the dried seaweeds and the soups were measured spectrophotometrically after digestion with hydrochloric acid and dilution with iodine free deionized water, as described by Benotti et al. (see Supplementary Data). The mean iodine content of the dried seaweed was 359 254 mg/g (mean SD), or 10173 7200mg/oz. The mean iodine content of seaweed broth was 1.9 0.7 mg/mL, with 1 bowl (250 mL) of broth containing an average of 487 178 mg of iodine. The mean iodine content of blended seaweed soup contents (broth, cooked seaweed) was 1705 930 mg/250 mL. Potential sources of variability in soup iodine (see Supplementary Data) include the iodine contents of dry seaweed and other ingredients (e.g., iodized salt, iodine-containing soy sauce, and anchovy soup base), cooking methodologies, and the quantity of seaweed in recipes (4). The iodine content of seaweed varies with harvest location and season, salinity and temperature of water, depth and portion of seaweed harvested, and storage conditions (4). The World Health Organization (WHO) guidelines recommend 250 mg/day of iodine intake during pregnancy and lactation, whereas the Institute of Medicine (IOM) recommends 220mg/day of iodine intake during pregnancy and 290 mg/day during lactation (Supplementary Data). The IOM recommends a tolerable upper limit of iodine intake of 1100mg/day, whereas the WHO suggests an upper limit of 500mg/day for pregnant and lactating women and 180mg/ day for infants. More than 90% of postpartum lactating Korean women consume seaweed soup at least three times daily in the first postpartum week, and up to 75% of these women have seaweed soup at least once daily up to 4 weeks postpartum (3). Our findings indicate that this constitutes an average iodine intake of at least 1400 mg/day in the first postpartum week based solely on 250 mL seaweed soup broth three times daily, and at least 5000mg/day if the entire contents of each serving are consumed (broth and seaweed). High levels of breast milk iodine values in Korean postpartum women have been reported (2,3). Depending on quantity and frequency of intake, postpartum women who consume Korean seaweed soup may have daily iodine intakes and breast milk iodine concentrations that far exceed the WHO and IOM upper limits. Iodine-induced hypothyroidism, iodine-induced thyrotoxicosis, and iodine-induced goiter are potential adverse effects of excess iodine consumption. However, the effects of high iodine intake are dependent on several factors, including iodine status (i.e., degree and duration of iodine deficiency or sufficiency) before excess iodine exposure, as well as any preexisting thyroid autoimmunity, thyroid dysfunction, and/or thyroid nodularity. Chung et al. reported subclinical hypothyroidism in preterm Korean infants exposed to high iodine content in breast milk (2). Additionally, cases of iodine-induced neonatal hypothyroidism due to maternal seaweed consumption were reported in Australia. Increased incidence and/or exacerbation of postpartum thyroiditis are also potential risks of high iodine intake. However, these effects were not observed in the only Korean study to date evaluating this relationship. Further studies should be carried out to evaluate the potential adverse effects of sustained high dietary iodine in postpartum women of Korean descent and their infants. In addition, there should be a raised cultural awareness among endocrinologists and other medical providers regarding this common source of high dietary iodine. A careful dietary history should be part of the evaluation and follow-up of postpartum Korean women and their infants, especially in the setting of signs and/or symptoms of thyroid dysfunction, thyroid autoimmunity, nodular thyroid anatomy, or pre-existing thyroid dysfunction. In addition, Korean women

Urine test strips as a source of iodine contamination.

In the course of conducting an analysis in a subset of the controlled antenatal thyroid screening study (1) samples, we recently noted that some urine samples from pregnant women in Wales, a region known to be iodine deficient, had urinary iodine concentrations in excess of 500mg=L. We suspected contamination from urine test strips. We obtained Combur Test D urine test strips (Roche Diagnostics, Mannheim, Germany), as were used in the Welsh study. We also obtained Multistix 10 SG urine test strips (Bayer Health Care, Elkhart, IN), used in our clinic, for comparison. Iodine was not mentioned in the package insets for either test strip. Two urine samples were obtained from healthy volunteers. Total urinary iodine concentrations were measured both spectrophotometrically by a modification of the method of Benotti et al. (2) and by mass spectroscopy. Measurements were obtained at baseline, after placing each test strip in the urine for 1 second, and again after placing each test strip in the urine for 30 seconds (Table 1). To determine which individual tests contained iodine, the test strips were cut into separate pieces for each test, and urine iodine concentrations were remeasured after placing individual pieces in a separate urine sample for 30 seconds. Iodine was present in the tests for glucose and blood in the Combur Test D and only in the Multistix test for glucose. The test strips for glucose rely on sequential reactions. First, glucose oxidase catalyzes the aerobic oxidation of glucose to gluconic acid and hydrogen peroxide. Second, in the presence of iodide, hydrogen peroxide oxidizes the iodide to free iodine, producing a color change in the indicator. The color change produced indicates the amount of hydrogen peroxide present, and therefore the glucose content of the urine. Although previously reported by Chanoine et al. (3) over 20 years ago, the contamination of urine with iodine by test strips is not well known. Since Combur and Multistix test strips still contain iodine as a reagent for blood and glucose testing, urine iodine concentrations should be assessed before test strip measurements. This is important in evaluating populations for iodine sufficiency. References

Iodine concentration in commercial cat foods from three regions of the USA, 2008–2009

Fluctuations in iodine concentration in food have been suggested as one risk factor for the development of feline hyperthyroidism, an epidemic disease first described in 1979. Three international studies have examined iodine concentrations of commercial cat foods. The iodine concentration of 112 commercial cat foods from across the USA was measured, and the daily iodine intake by hypothetical 4.5 kg adult cats or 1.4 kg kittens calculated in this descriptive epidemiologic study to examine differences in feline iodine intake due to (i) geographical source of foods, (ii) packaging type, (iii) brand-to-brand variation, (iv) form of iodine supplementation, (v) types and numbers of seafood ingredients and (vi) kitten and ‘therapeutic’ diets. Dramatic variation among canned foods (resulting in ingestion of approximately 49–9639 μg iodine/day) suggests that the disparity in iodine concentrations may lead to development of nodular hyperplasia and, later, clinical hyperthyroidism, if cats consume diets that are at first iodine-deficient and later contain excessive iodine. Manufacturers are encouraged to ensure adequate iodine supplementation across all products and areas of the USA.