The Joint Role of Thyroid Function and Iodine Status on Risk of Preterm Birth and Small for Gestational Age: A Population-Based Nested Case-Control Study of Finnish Women.

Normal maternal thyroid function during pregnancy is essential for fetal development and depends upon an adequate supply of iodine. Little is known about how iodine status is associated with preterm birth and small for gestational age (SGA) in mildly iodine insufficient populations. Our objective was to evaluate associations of early pregnancy serum iodine, thyroglobulin (Tg), and thyroid-stimulating hormone (TSH) with odds of preterm birth and SGA in a prospective, population-based, nested case-control study from all births in Finland (2012-2013). Cases of preterm birth (n = 208) and SGA (n = 209) were randomly chosen from among all singleton births. Controls were randomly chosen from among singleton births that were not preterm (n = 242) or SGA (n = 241) infants during the same time period. Women provided blood samples at 10-14 weeks' gestation for serum iodide, Tg and TSH measurement. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for preterm birth and SGA. Each log-unit increase in serum iodide was associated with higher odds of preterm birth (adjusted OR = 1.19, 95% CI = 1.02-1.40), but was not associated with SGA (adjusted OR = 1.01, 95% CI = 0.86-1.18). Tg was not associated with preterm birth (OR per 1 log-unit increase = 0.87, 95% CI = 0.73-1.05), but was inversely associated with SGA (OR per log-unit increase = 0.78, 95% CI = 0.65-0.94). Neither high nor low TSH (versus normal) were associated with either outcome. These findings suggest that among Finnish women, iodine status is not related to SGA, but higher serum iodide may be positively associated with preterm birth.

[Status of lactating women's iodine nutrition and thyroid function in different iodine nutrition level of children in Gansu Province].

OBJECTIVE: To assess the iodine nutrition and thyroid function of lactatingwomen in different iodine nutrition level of children in Gansu Province, and provide a scientific basis for iodine supplementation. METHODS: Liangzhou district( the median urinary iodine was greater than or equal to 300 g/L), Linze county( the median urinary iodine was from 200 to 299 g/L) and Huating county( the median urinary iodine was from100 to 199 g/L) were selected according to 8-10 years old children urinary iodine in2009. Huating county, Liangzhou district and Linze county were as iodine excessive area, iodine suitable area 1 and iodine suitable area 2, respectively in 2014. One township was randomly selected from the east, west, south, north and middle parts of each research point, 10 lactating women were randomly collected in each township, who was tested urine samples and thyroid function. Salt intake was surveyed in 3 townships. 2 samples were collected in centralized water supplies, 1 sample was collected in its coverage by the east, west, south, north and middle parts; 1 sample was collected by the east, west, south, north and middle parts in decentralized water supplies, which were tested of water iodine. RESULTS: The medians of water iodine were 2. 32, 0. 70 and 6. 18 µg/L and the medians of salt iodine were 25. 3, 25. 0 and 28. 6 mg/kg for iodine excessive area, iodine suitable area 1 and iodine suitable area 2, respectively. Per capita daily intake of salt were 15. 0, 11. 3 and 4. 7 g for iodine excessive area, iodine suitable area 1 and iodine suitable area 2 respectively, there were statisticant differences. The median urinary iodine of lactating women were 181. 8, 143. 1 and 104. 9 µg/L for iodine excessive area, iodine suitable area 1 and iodine suitable area 2, respectively. The medians of thyroidstimulating hormone( TSH) were 2. 3, 2. 2 and 1. 9 mIU/L, mean values of free thyroxine( FT4) were 15. 0, 13. 9 and 14. 6 pmol/L, mean values of free triidothyronine( FT3) were 5. 0, 4. 8 and 4. 6 pmol/L for iodine excessive area, iodine suitable area 1 and iodine suitable area 2 respectively, there were not statistically differences. The positive rate of thyromicrosomal antibody( Tm Ab) were 3. 6 %, 11. 3 % and 13. 2 % and the positive rate of thyroglobulin antibody( Tg Ab) were 3. 6 %, 11. 3 % and 11. 3 % for iodine excessive area, iodine suitable area 1 and iodine suitable area 2 respectively( P >0. 05). Prevalence of thyroid function disorders were 14. 3 %, 21. 0 % and 9. 4 % and prevalence of low-FT4 syndrome were 7. 1 %, 4. 8 % and 1. 9 %, prevalence of subclinical hypothyroidism were 3. 6 %, 11. 3 % and 3. 8 % for iodine excessive area, iodine suitable area 1 and iodine suitable area 2 respectively( P > 0. 05). CONCLUSION: Iodine nutrition level was appropriate for lactating women in 3 areas, but some lactating women were iodine deficiency or iodine excess. There were occurred thyroid function disorders in some lactating women in 3 areas. The lactating women's iodine nutrition and thyroid function should be monitored and the normal reference value of thyroid function on lactating women should be established also.

Carbon dots-based fluorescent probe for "off-on" sensing of Hg(II) and I⁻.

Herein, we report a simple, one-step reflux method for synthesis of photoluminescent carbon dots (CDs) using citric acid as the carbon source and diethylenetriamine (DETA) as the surface passivation reagent along with a high quantum yield (82.40%), the fluorescence intensity of the CDs was found to be effectively quenched by Hg(II) ions. Upon addition of I(-) to the CDs/Hg(II) complex dispersion, the fluorescence intensity of the CDs was significantly recovered. Furthermore, we developed an "off-on" fluorescence assay for the detection of I(-) using CDs/Hg(II) as a fluorescence probe. This probe enables the selective detection of Hg(II) with a linear range of 0-80 µM and a limit of detection is 0.201 µM and a limit of detection about I(-) is 0.234 µM with a linear range of 0-70 µM. Most importantly, the sensors can be successfully applied to the determination of Hg(II) and I(-) in real lake water and urine of cattles, the "off-on" sensor demonstrates high selectivity, repeatability, stability, which offer this CDs-based "off-on" fluorescent sensor a promising platform for environmental and biological sensing applications.

Micro Ion Extractor for Single Drop Whole Blood Analysis.

A micro ion extractor (MIE) was developed for trace anion determination by ion chromatography-mass spectrometry from a single drop (25 µL) of whole blood without pretreatment. Target analytes were iodide and thiocyanate, which play key roles in thyroid hormone production. Whole blood (25 µL) was pipetted from an earlobe or finger prick and placed in the 16 µL cavity of the device. A reproducible fraction of iodide and thiocyanate was transferred through a membrane to an acceptor solution layer by electromigration for 60 s. An isolator solution layer and a cation exchange membrane is provided between the acceptor and the anode to prevent gas formation or redox processes in the acceptor. The acceptor contents are transferred online to the ion chromatograph. Isolator solution composition and applied voltage were optimized. Recoveries from samples from 16 different volunteers of both sexes and differing ages were the same within ±10% relative standard deviation. Dietary effects on blood iodide and thiocyanate levels are reported. The very low sample requirement permitted multiple sample collections per day. The MIE device is expected to be useful for clinical studies that require several/many temporally spaced blood samples by keeping the invasive nature of blood collection as minimal as possible.

Fluorescent organic nanoparticles of dihydropyrimidone derivatives for selective recognition of iodide using a displacement assay: application of the sensors in water and biological fluids.

Fluorescent organic nanoparticles (FON's) derived from dihydropyrimidone derivatives (1-4) were developed and evaluated for their sensor properties. Nano-aggregates of compound 3 and 4 resulted in sensors. Nano-aggregates of compound 3 showed enhancement in the monomer peaks of the pyrene moiety after the addition of mercury. Nano-aggregates of compound 4 resulted in quenching of intensity upon addition of Hg(2+). On the other hand, no sensor activity was recorded for nano-aggregates of compounds 1 and 2. Further, the complex of nano-aggregates of 3 and mercury (3·Hg(2+)) recognised iodide ions by showing quenching in monomer and excimer emission with a detection limit of 0.2 nM in aqueous medium; however the resultant metal complex 4·Hg(2+) does not show any anion sensing activity. Receptor 3·Hg(2+) has a highly sensitive and selective response toward I(-) ions. Therefore, the iodide content of tap water, urine and blood serum is monitored using this sensor and it is found that the sensor can detect a range of iodide in tap water, urine and blood serum. To the best of our knowledge, the system represents the first example of iodide recognition using FONs.

Characterization of a rapid and reliable method for iodide biomonitoring in serum and urine based on ion chromatography-ICP-mass spectrometry.

An appropriate and controlled supply of thyroid hormones is vital for proper body function. In turn, an appropriate synthesis of T3 and T4 in the thyroid gland is dependent on a sufficient and balanced iodide concentration in blood serum. Due to widespread iodine deficiency or some cases of iodine over exposure, iodide biomonitoring in serum is important and it is that biomonitoring approach being closest to the bioavailable I(-) supply for the thyroid gland. Therefore, this paper describes a biomonitoring method for iodide determination in serum based on ion chromatography-inductively coupled plasma mass spectrometry (IC-ICP-MS). Since in literature only very few data are available on iodide in serum but many in urine the method is also extended to I(-) monitoring in urine. The method was additionally designed to have short analysis time (8min) for increased sample throughput, good precision in serial measurement (serum: 4.86%; urine: 1.4%), and day-to-day determination (serum: 5.7%; urine: 2.28%), high accuracy (serum: 105%; urine: 101%) and good recovery (serum: 102%; urine: 99%) even in matrix-rich samples at low I(-) concentration. Also, investigations were performed to elucidate whether internal standardization during chromatography, sample preparation for protein-matrix removal or matrix-matched calibration are advantageous for analytical performance. Finally, limits of detection (3σ) of 0.12µg/L or 0.05µg/L (serum or urine) and limit of quantification (10σ) of 0.39µg/L or 0.17µg/L (serum or urine) were achieved.

Occurrence of perchlorate and thiocyanate in human serum from e-waste recycling and reference sites in Vietnam: association with thyroid hormone and iodide levels.

Perchlorate (ClO4 (-)) and thiocyanate (SCN(-)) interfere with iodide (I(-)) uptake by the sodium/iodide symporter, and thereby these anions may affect the production of thyroid hormones (THs) in the thyroid gland. Although human exposure to perchlorate and thiocyanate has been studied in the United States and Europe, few investigations have been performed in Asian countries. In this study, we determined concentrations of perchlorate, thiocyanate, and iodide in 131 serum samples collected from 2 locations in Northern Vietnam, Bui Dau (BD; electrical and electronic waste [e-waste] recycling site) and Doung Quang (DQ; rural site) and examined the association between serum levels of these anions with levels of THs. The median concentrations of perchlorate, thiocyanate, and iodide detected in the serum of Vietnamese subjects were 0.104, 2020, and 3.11 ng mL(-1), respectively. Perchlorate levels were significantly greater in serum of the BD population (median 0.116 ng mL(-1)) than those in the DQ population (median 0.086 ng mL(-1)), which indicated greater exposure from e-waste recycling operations by the former. Serum concentrations of thiocyanate were not significantly different between the BD and DQ populations, but increased levels of this anion were observed among smokers. Iodide was a significant positive predictor of serum levels of FT3 and TT3 and a significant negative predictor of thyroid-stimulating hormone in males. When the association between serum levels of perchlorate or thiocyanate and THs was assessed using a stepwise multiple linear regression model, no significant correlations were found. In addition to greater concentrations of perchlorate detected in the e-waste recycling population, however, given that lower concentrations of iodide were observed in the serum of Vietnamese females, detailed risk assessments on TH homeostasis for females inhabiting e-waste recycling sites, especially for pregnant women and their neonates, are required.

Organizational changes to thyroid regulation in Alligator mississippiensis: evidence for predictive adaptive responses.

During embryonic development, organisms are sensitive to changes in thyroid hormone signaling which can reset the hypothalamic-pituitary-thyroid axis. It has been hypothesized that this developmental programming is a 'predictive adaptive response', a physiological adjustment in accordance with the embryonic environment that will best aid an individual's survival in a similar postnatal environment. When the embryonic environment is a poor predictor of the external environment, the developmental changes are no longer adaptive and can result in disease states. We predicted that endocrine disrupting chemicals (EDCs) and environmentally-based iodide imbalance could lead to developmental changes to the thyroid axis. To explore whether iodide or EDCs could alter developmental programming, we collected American alligator eggs from an estuarine environment with high iodide availability and elevated thyroid-specific EDCs, a freshwater environment contaminated with elevated agriculturally derived EDCs, and a reference freshwater environment. We then incubated them under identical conditions. We examined plasma thyroxine and triiodothyronine concentrations, thyroid gland histology, plasma inorganic iodide, and somatic growth at one week (before external nutrition) and ten months after hatching (on identical diets). Neonates from the estuarine environment were thyrotoxic, expressing follicular cell hyperplasia (p = 0.01) and elevated plasma triiodothyronine concentrations (p = 0.0006) closely tied to plasma iodide concentrations (p = 0.003). Neonates from the freshwater contaminated site were hypothyroid, expressing thyroid follicular cell hyperplasia (p = 0.01) and depressed plasma thyroxine concentrations (p = 0.008). Following a ten month growth period under identical conditions, thyroid histology (hyperplasia p = 0.04; colloid depletion p = 0.01) and somatic growth (body mass p<0.0001; length p = 0.02) remained altered among the contaminated sites. This work supports the hypothesis that embryonic EDC exposure or iodide imbalance could induce adult metabolic disease states, thereby stressing the need to consider the multiple environmental variables present during development.

Diagnosis of iodide transport defect: do we need to measure the saliva/serum radioactive iodide ratio to diagnose iodide transport defect?

BACKGROUND: Iodide transport defect (ITD) is an infrequent condition associated with congenital dyshormonogenetic goiter due to mutations in the Na(+)/I(-) symporter (NIS) gene transmitted in an autosomal recessive manner. Herein, we describe a patient with ITD and discuss the features important for the diagnosis, focusing on whether or not measuring the saliva/serum radioactive iodide ratio is useful. SUMMARY: A 42-year-old Japanese man attended our hospital in 2010. At that time, he had been off L-thyroxine for several months. He had no obvious mental retardation. His parents were cousins and his sister also had a goiter. Since thyroid dyshormonogenesis could not be ruled out, thyroid function tests, scintigraphy, and ultrasonography were performed. The results showed marked hypothyroidism with a high thyroglobulin level of 627 ng/mL. The results for thyroglobulin antibody and thyroid peroxidase antibody were both negative. Ultrasonography showed an enlarged thyroid gland. Neither the thyroid nor the salivary gland was visualized by (99m)TcO(4)(-) scintigraphy. Therefore, we performed genetic testing for the NIS gene without measuring the saliva/serum radioactive iodide ratio. A homozygous mutation, T354P, was identified in the NIS gene. On the basis of this finding, we could make the definitive diagnosis of ITD due to an NIS mutation. CONCLUSIONS: We recommend confirming the presence of the thyroid by ultrasonography of the neck first and then performing (99m)TcO(4)(-) scintigraphy. If neither the salivary gland nor the thyroid is visualized, screening for NIS mutations should be undertaken. This approach obviates the need to undertake measurement of the saliva/serum radioactive iodide ratio to diagnose ITD.

Perchlorate and iodide in whole blood samples from infants, children, and adults in Nanchang, China.

Perchlorate, ClO(4)(-), interferes with iodide (I(-)) uptake by the sodium-iodide symporter (NIS) and thereby affects thyroid hormone production in the body. Studies have reported human exposures to perchlorate based on measurements in urine, but little is known about the levels in blood. In this study, we determined concentrations of perchlorate, iodide, and other anions (e.g., chlorate [ClO(3)(-)], bromate [BrO(3)(-)], bromide [Br(-)]) in 131 whole blood samples collected from Chinese donors aged 0.4 to 90 yr, in Nanchang, China. Perchlorate, iodide, and bromide were detected in all of the samples analyzed, whereas chlorate was found in only 27% of the samples and bromate was found in only 2%. The mean (range) concentrations of perchlorate, iodide, and bromide were 2.68 (0.51-10.5), 42.6 (1.58-812), and 2120 (1050-4850) ng/mL, respectively. Perchlorate levels in blood from Nanchang adults were 10-fold greater than levels that have been previously reported for U.S. adults. The iodide/perchlorate molar ratio ranged from 3.05 to 15.3 for all age groups, and the ratio increased with age (r = 0.732, p < 0.01). Perchlorate and bromide concentrations decreased significantly with age, whereas iodide concentrations increased with age. No significant gender-related differences in blood perchlorate, iodide, or bromide levels were found. A significant negative correlation was found between the concentrations of perchlorate and iodide in blood. Exposure doses of perchlorate were estimated for infants, toddlers, children, adolescents, and adults based on the measured concentrations in blood, using a simple pharmacokinetic model. The mean exposure doses of perchlorate for our age groups ranged from 1.12 (adults) to 2.22 µg/kg bw/day (infants), values higher than the United States Environmental Protection Agency's (USEPA) reference dose (RfD: 0.7 µg/kg bw/day). This is the first study on perchlorate and iodide levels in whole blood from infants, toddlers, children, adolescents, and adults from a city in China with known high perchlorate levels.

Development and validation of an assay for iodide in serum using ion chromatography with pulsed amperometric detection.

We developed and validated an ion chromatography method to assay iodide in serum sampled from rats and rabbits that had been exposed to iodomethane. Iodomethane is of interest because it is a volatile liquid pre-plant soil crop protection fumigant that has been proposed as a non-ozone-depleting alternative to methyl bromide. Serum was prepared from whole blood collected on wet ice at the time of sacrifice and kept frozen at less than -65 degrees C. For analysis, serum samples were thawed unassisted at ambient temperature. Proteins were separated from the serum samples by ultrafiltration. A 100-microl filtered serum sample was then injected into the ion chromatograph without additional sample preparation. Iodide was separated in <20 min by anion-exchange chromatography using a 25-mM nitric acid eluent. The analyte of interest was detected by pulsed amperometry using a silver working electrode. The method showed linear response over the concentration range of 100 to 5000 ng/ml iodide (r2>.998) with a lower limit of quantitation of 100 ng/ml iodide. The accuracy of the procedure, determined by spiked recovery measurements at 100 ng/ml iodide, was between 90 and 110%. A method detection limit of 20 ng/ml for iodide in serum samples was demonstrated using the method of standard additions.

Iodide concentrations in matched maternal serum, cord serum, and amniotic fluid from preterm and term human pregnancies.

OBJECTIVES: To characterize the matched maternal and cord plasma and the amniotic fluid concentrations of iodide in preterm and term human pregnancies. METHODS: Specimens were collected at the delivery of 121 singleton pregnancies (92 at term, 29 preterm) with no pre-existing medical complications. Plasma unbound iodide concentrations were measured by the difference between the protein bound iodine and the total iodine measured spectrophotometrically. Total iodide was measured in amniotic fluid. RESULTS: Maternal plasma iodide concentrations were 1.6 +/- 0.4 mcg/dL (mean +/- S.D.) for preterm deliveries and 1.5+/ -0.5 mcg/dL for term deliveries. Cord plasma iodide concentrations were 1.4 +/- 0.5 mcg/dL for preterm deliveries and 1.7 +/- 0.7 mcg/dL for term deliveries. Cord plasma iodide concentrations at birth correlated highly with maternal levels (p < 0.001). The cord:maternal plasma iodide ratio for all pairs was 1.2+/- 0.7. The average cord:maternal plasma iodide ratio was not significantly different between the preterm (0.9+/- 0.4) and term (1.3+/- 0.8) deliveries. Amniotic fluid iodide concentrations did not correlate significantly with cord plasma concentrations. CONCLUSION: Cord plasma concentrations of iodide correlate with paired maternal levels, indicating that, unlike the rabbit and other species, the human conceptus does not highly concentrate iodide.

Determination of iodide in samples with complex matrices by hyphenation of capillary isotachophoresis and zone electrophoresis.

A method has been developed for the determination of iodide in mineral water, seawater, cooking salt, serum, and urine based on hyphenation of capillary ITP and zone electrophoresis. A commercially available instrumentation for capillary ITP with column-switching system was used. ITP served for removal of chloride present in the analyzed samples in a ratio of 10(6)-10(7):1 to iodide, zone electrophoresis was used for evaluation. Isotachophoretic separation proceeded in a capillary made of fluorinated ethylene-propylene copolymer of 0.8 mm id and 90 mm total length to the bifurcation point filled with a leading electrolyte (LE) composed of 8 mM HCl + 16 mM beta-alanine (beta-Ala) + 10% PVP + 2.86 mM N(2)H(4)x2HCl, pH 3.2; and a terminating electrolyte composed of 8 mM H(3)PO(4) + 16 mM beta-Ala + 10% PVP + 5 mM N(2)H(4), pH 3.85 for all the matrices except seawater. For ITP of seawater the LE consisted of 50 mM HCl + 100 mM beta-Ala + 10% PVP + 2.86 mM N(2)H(4)x2HCl, pH 3.52. Distance of conductivity detector from the injection point and bifurcation point was 52 and 38 mm, respectively. Zone electrophoresis was performed in a capillary made of fused silica of 0.3 mm id and 160 mm total length filled with LE from isotachophoretic step. LODs reached for all matrices were 2-3x10(-8) M concentration (2.5-4 microg/L) enabled monitoring of iodide in all analyzed samples with RSD 0.4-9.3%. Estimated concentrations of iodide in individual matrices were 10(-6)-10(-8) M.

Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease.

OBJECTIVE: After primary successful antithyroid drug treatment (ATDT), Graves' disease has a relapse rate of 30% to 50%. Previous studies have evaluated age, gender, goiter volume, smoking habits, and the presence of thyrotropin-receptor antibodies (TRAb) as predictive markers to facilitate an individualized patient management. Despite higher sensitivity and specificity of the new second generation human TSH-receptor assay, the predictive value of TRAb for relapse of hyperthyroidism is still controversial. In a recent prospective multicenter study we have previously shown that suppressed or low TSH values predict both early (persistence) and late relapse of Graves' disease. We now present a more detailed analysis of the predictive value of TSH and TRAb for recurrent hyperthyroidism. METHODS: Four weeks after withdrawal of ATDT, 96 patients were available for thyroid function tests, including a sensitive third-generation TSH assay and a second-generation recombinant TSH receptor assay. Relapse of Graves' disease was evaluated for a total follow-up of 2 years. RESULTS: Within 2 years, 47 of 96 patients (49%) developed relapse of hyperthyroidism. Nine patients relapsed within the first 4 weeks after withdrawal of ATDT and were thus considered to have persistent Graves' disease. Ten of 15 other patients with TSH levels below 0.3 mU/L without overt hyperthyroidism relapsed within 2 years. Twenty-five of 65 patients with normal TSH (0.3-3.0 mU/L) and 3 of 4 patients with TSH values above 3 mU/L also had recurrent hyperthyroidism. After ATDT cessation, TSH had a positive predictive value of 70% and a negative predictive value of 62% (specificity 85%) for relapse of Graves 'disease. Mean TRAb levels in the group of patients with relapse were significantly higher (11.1 IU/L +/- 0.17) than TRAb values in the remission group (4.5 IU/L +/- 0.6), p < 0.001. Using a cutoff value of 1.5 IU/L, TRAb had low positive and negative predictive values of 49% and 54%, respectively (specificity, 14%), but with a cutoff level of 10 IU/L, predictive values improved to 83% and 62%, respectively (specificity, 92%). Combination of TSH and TRAb determinations did not further improve prediction of relapse. Other factors such as gender, age, goiter volume, smoking habits, presence of thyroid-associated ophthalmopathy, and urinary iodine excretion did not show a significant influence on relapse rate. CONCLUSION: Low TSH values 4 weeks after ATDT withdrawal predict relapse of Graves' disease, both early (persistence) and, to a lesser extend, within 2 years of follow-up. Also, TRAb above 10 IU/L found in a small subset of patients, correlated with a higher relapse rate.

Sensitive flow-injection amperometric detection of iodide using Mn3+ and As3+.

A rapid, selective, and sensitive kinetic flow-injection method for iodide content determination with amperometric detection on a platinum electrode was developed. The method is based on the catalytic effect of iodide on the Mn3+ reaction with As3+ in the presence of sulfuric acid. The calibration curve was linear in the concentration range from 5.0 x 10(-7) to 1.0 x 10(-4) mol/L iodide. The limit of detection (LOD) was found to be 5.0 x 10(-9) mol/L iodide. The relative standard deviations (RSD) were 1.68% and 3.03% for 1.0 x 10(-3) mol/L standard and 1.0 x 10(-6) mol/L iodide solution (n = 6), respectively. The method has been successfully applied for determination of iodide in waters, table salts, fodder, organic substances and human blood sera. The results were compared with those obtained by a standard AOAC (Association of Official Analytical Chemists) method, as well as with those obtained by a kinetic spectrophotometric procedure for determination of iodide.

Do thyroxine and thyroid-stimulating hormone levels reflect urinary iodine concentrations?

The toxicity of environmental chemicals such as nitrates, thiocynates, and perchlorates, some therapeutics, and dietary goitrogens can lower thyroidal iodine uptake and result in hypothyroidism and goiter. Iodine sufficiency, essential for normal thyroid hormone synthesis, is critical during gestation to assure that sufficient thyroxine (T4) and iodine reach the developing fetus. Spot urinary iodide (UI) measurements are used globally to indicate and monitor iodine sufficiency of populations. In individuals, however, UI are not routinely measured; instead, normal serum thyroid-stimulating hormone (TSH) and T4 concentrations serve as surrogate indicators of iodine sufficiency as well as thyroidal health. Our objective was to examine the relationship between UI concentrations and serum T4 and TSH concentrations in individuals in an "iodine-sufficient population." Using a cross-sectional sample of the US population (n = 7628) from the National Health and Nutrition Examination Survey (NHANES III; 1988-1994) database, we examined the relationship among UI, T4, and TSH in pregnant and nonpregnant women and in men (15-44 years). There was a lack of relationship between UI (or UI/Cr) concentrations and serum T4 or TSH concentrations. Therefore, TSH and T4 are not appropriate markers of UI concentrations in this population. Monitoring the status of iodine nutrition of individuals in the United States may be important because serum TSH and T4 concentrations do not indicate low iodine status.

Fast and simple method for determination of iodide in human urine, serum, sea water, and cooking salt by capillary zone electrophoresis.

For the determination of iodide in urine, where 80-90% of consumed iodine is excreted, a fast, simple, and sensitive method of capillary zone electrophoresis was elaborated and tested also for additional complex matrices such as human serum, cooking salt, and seawater. Several approaches were examined for the separation of iodide from other macro- and microcomponents in the tested matrices, and the best results were obtained when host-guest interaction with alpha-cyclodextrin or ion-pairing with polyethylenimine was employed. In both cases comparable resolution and sensitivity were reached. Due to the relatively high price of cyclodextrin only the method with polyethylenimine was further optimized and a simple procedure enabling the determination of iodide in untreated human urine, serum, cooking salt, and seawater was elaborated. The samples were injected for 20 s at 0.5 psi (3.45 kPa) into a fused-silica capillary (0.18 mm ID, 50 cm effective length) coated with polyacrylamide (electroosmotic flow < 2 x 10(-9) m(2)V(-1)s(-1)) and filled with the optimized background electrolyte composed of 20 mM KH(2)PO(4) and 0.7% m/v polyethylenimine. For detection, UV absorption at 200 and 230 nm was measured. Concentration limits of detection reached at 230 nm were for human urine 0.14 microM, for human serum 0.17 microM, for seawater 0.17 microM, and for cooking salt 89 nM. Relative standard deviations of iodide peak area and height in all matrices ranged within 0.93 to 4.19%.

Relapse of Graves' disease after successful outcome of antithyroid drug therapy: results of a prospective randomized study on the use of levothyroxine.

Antithyroid drugs are effective in restoring euthyroidism in Graves' disease, but many patients experience relapse after withdrawal. Prevention of recurrence would therefore be a desirable goal. In a prospective study, patients with successful outcome of 12 to 15 months antithyroid drug therapy were stratified for risk factors and randomly assigned to receive levothyroxine in a variable thyrotropin (TSH)-suppressive dose for 2 years or no treatment. The levothyroxine group was randomized to continue or discontinue levothyroxine after 1 year. End points included relapse of overt hyperthyroidism. Of 346 patients with Graves' disease enrolled 225 were euthyroid 4 weeks after antithyroid drug withdrawal and were randomly assigned to receive levothyroxine (114 patients) or no treatment (controls, 111 patients). Of those not randomized, 39 patients showed early relapse within 4 weeks, 61 endogenous TSH suppression, 7 TSH elevation, and 14 had to be excluded. Dropout rate during the study were 13.3%. Kaplan-Meier analyses showed relapse rates to be similar in the levothyroxine group (20% after 1 year, 32% after 2 years) and the randomized controls (18%, 24%), whereas relapses were significantly more frequent in the follow-up group of patients with endogenously suppressed TSH (33%, 49%). Levothyroxine therapy did not influence TSH-receptor antibody, nor did it reduce goiter size. The best prognostic marker available was basal TSH determined 4 weeks after withdrawal of antithyroid drugs (posttreatment TSH). The study demonstrates that levothyroxine does not prevent relapse of hyperthyroidism after successful restoration of euthyroid function by antithyroid drugs and characterizes posttreatment TSH as a main prognostic marker.

Phenotypes associated with replacement of His by Arg in the Pendred syndrome gene.

BACKGROUND: Pendred syndrome is often associated with inner ear malformations, especially enlarged vestibular aqueduct (EVA). Recently, mutations in the Pendred syndrome gene (PDS) have been reported in patients with EVA, in addition to those with classical Pendred syndrome. OBJECTIVE: The aim of this study was to investigate the genotype-phenotype correlations of PDS. METHODS: Each of the 21 exons and flanking splice regions of PDS was analysed by direct DNA sequencing in nine patients with EVA; allele-specific amplification was performed to confirm the mutation. Genetic analyses were compared with thyroid function tests, perchlorate discharge tests, thyroid volume and pure-tone audiogram. Magnetic resonance imaging was used to determine the volume of the endolymphatic duct and sac of each patient. RESULTS: A missense mutation, H723R, was identified in the homozygous state in three patients and in the heterozygous state in another three. Although none of the patients had goitre, increased serum thyroglobulin and an abnormal degree of iodide release were correlated with the number of mutant alleles identified. However, there was no relationship between the degree of hearing loss and the number of mutant alleles. CONCLUSION: The present study reveals that the number of mutant alleles correlates with the degree of subclinical thyroid abnormality, but not with the degree of hearing loss in Japanese patients with the PDS missense mutation H723R.