Serum Iodide Research Articles

Iodine and thyroid status during pregnancy and risk of stillbirth: A population-based nested case-control study.

Prior research suggests that severe iodine deficiency in pregnancy may be associated with stillbirth. However, the relationship between mild to moderate iodine insufficiency, which is prevalent even in developed countries, and risk of stillbirth is unclear. We thus examined associations of iodine status and risk of stillbirth in a prospective population‐based nested case–control study in Finland, a mild to moderately iodine insufficient population. Stillbirth cases (n = 199) and unaffected controls (n = 249) were randomly selected from among all singleton births in Finland from 2012 to 2013. Serum samples were collected between 10 and 14 weeks gestation and analysed for iodide, thyroglobulin (Tg) and thyroid‐stimulating hormone (TSH). Odds ratios (ORs) and 95% confidence intervals (CIs) for stillbirth were estimated using logistic regression. After adjusting for maternal age, prepregnancy body mass index, socio‐economic status and other factors, neither high nor low serum iodide was associated with risk of stillbirth (Q1 vs. Q2–Q3 OR = 0.92, 95% CI = 0.78–1.09; Q4 vs. Q2–Q3 OR = 0.78; 95% CI = 0.45–1.33). Tg and TSH were also not associated with risk of stillbirth in adjusted models. Maternal iodine status was not associated with stillbirth risk in this mildly to moderately iodine‐deficient population. Tg and TSH, which reflect functional iodine status, were also not associated with stillbirth risk. The lack of associations observed between serum iodide, TSH and Tg and risk of stillbirth is reassuring, given that iodine deficiency in pregnancy is prevalent in developed countries.

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.

The joint role of thyroid function and iodine concentration on gestational diabetes risk in a population-based study.

Iodine is essential for thyroid function, and iodine deficiency during pregnancy is common in Europe and the USA. However, no published studies have examined the role of iodine deficiency in the relation between thyroid function and gestational diabetes mellitus (GDM). We conducted a population-based, nested case-control study within the Finnish Maternity Cohort using pregnancy and perinatal outcome data from the Finnish Maternal Birth Register. We randomly selected 224 GDM cases with singleton pregnancies and 224 controls without GDM from all singleton births occurring in Finland during 2012-2013. Blood was drawn at 10-14weeks' gestation and analyzed for serum iodide, thyroglobulin, and thyroid-stimulating hormone (TSH) concentrations. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) of GDM. Very high thyroglobulin concentration (>95% percentile; >83μg/L) was not associated with significantly altered odds of GDM compared to those with normal levels (OR 0.41; 95% CI: 0.12, 1.38). High concentrations of TSH were also not associated with increased odds of GDM compared to normal levels of TSH (OR 0.45; 95% CI: 0.06, 3.18). Women in the lowest 5th percentile (<1.58ng/mL) of iodine did not have increased odds of GDM compared to those with iodide in the highest quartile (OR 0.39; 95% CI: 0.11, 1.35). Low levels of iodide and thyroid function in early pregnancy are not associated with increased risk of GDM in this mildly iodine-deficient population.

Monolateral Sialadenitis Following Iodinated Contrast Media Administration for Carotid Artery Stenting

We describe the occurrence of monolateral aseptic sialadenitis following non-iodinated contrast medium (ICM) administration for a carotid artery stenting procedure in a 71-year-old man. The mechanism for iodide-induced sialadenitis may be idiosyncratic or related to toxic accumulation of iodide. The risk for sialadenitis is directly related to serum iodide levels (> 10 mg/100 mL) and inversely related to normal renal function so that in renal impairment, ICM can be eliminated through alternative pathways such as the salivary glands and other excretory organs.

Kinetics of acute and chronic iodine excess.

Iodine plays an important role in thyroid physiology resulting from its importance as a requisite substrate for the synthesis of thyroid hormones and from its action as a regulator of thyroid function. Following intestinal absorption, inorganic iodide is largely confined to the extracellular fluid. Serum concentrations of inorganic iodide well reflect the amount of iodine present in the extracellular compartment. Since serum inorganic iodide levels are important determinants of thyroid iodine uptake, serum iodide measurement offers a valuable tool for the investigation of many basic and clinical aspects of thyroid iodine metabolism. Here we summarize important aspects of iodine metabolism and focus selectively on technical aspects of serum inorganic iodide measurement and on the kinetics of inorganic iodide in various states of iodine excess. Presently, paired-ion, reversed-phase HPLC with electrochemical detection is obviously the best method for measurement of serum inorganic iodide being highly sensitive, easy to perform, and almost completely insensitive to interfering substances. Using this method, we could demonstrate an acute increase of serum inorganic iodide during the administration of large amounts of iodide as Lugol's solution given preoperatively in patients with Graves' hyperthyroidism. In patients under treatment with the iodine containing drug amiodarone (n=37), serum inorganic iodide levels were highly elevated (range 3.5-208.2 microg/dl, median 36.6 microg/dl). Serum concentrations of inorganic iodide were correlated neither to the daily amiodarone dose, nor to the serum levels of amiodarone.

Evaluation of respiratory parameters in rats and rabbits exposed to methyl iodide

Laboratory animals exposed to methyl iodide (MeI) have previously demonstrated lesions of the olfactory epithelium that were associated with local metabolism in the nasal tissues. Interactions of MeI in the nasal passage may, therefore, alter systemic toxicokinetics. The current study used unrestrained plethysmographs to determine the MeI effect on the breathing frequency and minute volume (MV) in rats and rabbits. Groups of 4 rats each were exposed to 0, 25, or 100 ppm and groups of 4 rabbits each were exposed to 0 and 20 ppm MeI for 6 h. Breathing frequency and MV were measured and recorded during the exposure. Blood samples were collected for inorganic serum iodide and the globin adduct S-methylcysteine (SMC) as biomarkers of systemic kinetics immediately following exposure. No significant reductions in breathing frequency were observed for either rats or rabbits. Significant changes in minute volume were demonstrated by both rats and rabbits; however, the changes observed in rats were not concentration dependent. The MeI-induced changes in MV resulted in significant differences in the total volume of test substance atmosphere inhaled over the 6-h period. Rats demonstrated a concentration-dependent increase in both inorganic serum iodide and SMC. Rabbits exposed to 20 ppm MeI demonstrated a significant increase of inorganic serum iodide; SMC was also increased but was not statistically significant. The results of this study are consistent with previous kinetic studies with MeI, and the data presented here can be integrated into a computational fluid dynamics physiologically based pharmacokinetic model for both rats and rabbits.

High-sensitivity capillary electrophoresis determination of inorganic anions in serum and urine using on-line preconcentration by transient isotachophoresis

Concentrations of inorganic anions, both as individual species and biotransformation products, in physiological fluids are of strong concern in clinical studies. To date, analytical methodologies have either required different analytical procedures to determine these analytes in plasma and urine, or extensive sample preparation, or unconventional and often expensive detection schemes, or both. A simple and sensitive capillary electrophoresis (CE) method with direct UV detection was developed for the simultaneous determination of iodide, bromide and nitrate in human plasma and urine, with a special focus on reliable quantification of the trace serum iodide. With the latter objective, the method incorporates a transient isotachophoresis (tITP) procedure enabling an efficient on-line preconcentration of iodide (limit of detection, 1.4 μg l −1) as well as other moderately mobile analytes that fall into the tITP range. The analyses of both types of biofluids were performed using an acidic electrolyte system composed of 0.25 mol l −1 sodium chloride and 7.5 mmol l −1 cetyltrimethylammonium chloride at pH 2.2 and 0.5 mol l −1 2-( N-morpholino)ethanesulfonate (pH 6.0) as terminating electrolyte. Relative standard deviations (R.S.D.) below 3.0% and 9.2% were obtained for within-day and between-day precision, respectively. Resolution and quantification of oxalic acid was also feasible under optimized tITP-CE conditions. Sample preparation required only ultrafiltration (serum) and dilution (urine). A number of plasma and urine samples were evaluated with this assay and the iodide, bromide and nitrate concentrations were in the expected clinical concentration ranges.

Effect of iodide on total antioxidant status of human serum

Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several degenerative and chronic diseases which are also treated frequently in spas. There are some data arising from previous studies which support an antioxidant or scavenging effect of iodide, being the essential ingredient of a therapeutically used local brine. The aim of the study was to test the antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total Antioxidant Status determined by a colorimetric method, which reflects the protection against the attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels achieved through balneo-therapeutical intervention. This result is in accordance with previous results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15 microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic acid (50 microM).

Effect of iodide on total antioxidant status of human serum.

Free radicals and subsequent lipid peroxidation have been implicated in the pathogenesis of several degenerative and chronic diseases which are also treated frequently in spas. There are some data arising from previous studies which support an antioxidant or scavenging effect of iodide, being the essential ingredient of a therapeutically used local brine. The aim of the study was to test the antioxidant capacity of iodide in human serum. For this reason we measured the so-called Total Antioxidant Status determined by a colorimetric method, which reflects the protection against the attack of reactive oxygen species, including enzymic and non-enzymic antioxidants. Exogenous iodide applied as NaI, shows a significantly increased antioxidant capacity in comparison with NaCl at a concentration of 15 microM, which is quite comparable to the upper range of serum iodide levels achieved through balneo-therapeutical intervention. This result is in accordance with previous results from in vitro depolymerization experiments with hyaluronic acid. The antioxidant effect of 15 microM NaI has been found to be approaching the physiologically relevant concentration of ascorbic acid (50 microM).

Contrast nephropathy with a non-ionic iodide medium in patients with normal and mildly impaired renal function

Effects of infusion of a non-ionic contrast medium(iopamidol, 370 mg l/ml) on renal function in a normovolemic state were examined in patients with normal and mildly affected renal function who underwent coronary angiography(CAG). The patients were divided into three groups: group I (n = 69) with serum creatinine(S-Cr) level < 1.0 mg/dl; group II (n = 50) with S-Cr level of 1.0 to 1.3 mg/dl and group III(n = 17) with S-Cr level of 1.3 to 2.0 mg/dl. Patients with S-Cr > or = 2.0 mg/dl were subjected to 3-h hemodialysis immediately after CAG(group HD, n = 11). Serum(S) and urine(U) values of Cr, Na, K, Cl, beta 2-microglobulin(beta 2MG), and U-N-acetyl-beta-D-glucosaminidase(NAG) were measured before and 24 h after CAG. U-NAG and U-beta 2MG were corrected for U-Cr, and fractional excretion of beta 2MG(FE beta 2MG) was determined. Basal U-NAG/Cr, U-beta 2MG/Cr and FE beta 2MG were increased in groups III and HD, suggesting the preexistence of tubular dysfunction. S-Cr was increased significantly only in group I, but there was no change in S-beta 2MG. U-NAG/Cr after CAG was elevated in all the groups, whereas U-beta 2MG/Cr(or FE beta 2MG) was increased only in group III. Greater than two-fold increases of U-NAG/Cr were noted equally in groups I through III. In contrast, the greater than two-fold increase of U-beta 2MG/Cr(or FE beta 2MG) occurred more frequently in group III as compared to the other groups. The incidences of such cases in group HD were similar to those of group III. The half life of serum iodide concentration was significantly shortened by 3-h HD(1.8 +/- 0.3 h vs. 15.9 +/- 3.8 h without HD). In conclusion, patients presenting S-Cr > or = 1.3 mg/dl were at high risk of renal tubular dysfunction even when contrast media was administered in the absence of significant increase in S-Cr. Whether an increase in U-NAG/Cr indicates tubular damage or is merely the result of tubular reabsorption of the agent remains to be clarified. Post-CAG hemodialysis efficiently eliminates contrast medium from the circulation.

Circulating iodide concentrations during and after pregnancy.

Early, indirect studies suggested that an important aspect of thyroid economy during pregnancy was a decline in plasma or serum inorganic iodide (PII) concentrations, but there is little information concerning circulating iodide concentrations as assessed by direct measurement. The present study was undertaken to determine the relationship between gestation and serum iodide concentrations as assessed by direct measurement of PII. PII concentrations, urinary iodide levels, and other parameters of thyroid economy were measured during the first, second, and third trimesters and after delivery in 16 women. Mean serum T4 concentrations were significantly higher in all 3 trimesters than those after delivery. Serum free T4 index concentrations were significantly higher in the first trimester than during later periods of gestation or after delivery, but serum TSH concentrations were not depressed in the first trimester. Serum thyroglobulin concentrations were similar during pregnancy and after delivery. There was wide variability in PII and urinary iodide concentrations during and after pregnancy, but there was no trend for PII concentrations to be depressed during pregnancy. Pregnancy, at least in iodine-sufficient regions, does not have an important influence on circulating concentrations of iodide.

Systemic iodine absorption during endoscopic application of radiographic contrast agents for endoscopic retrograde cholangiopancreaticography.

Hyperthyroidism induced by contrast agents in a major problem in patients with pre-existing thyroid disease, particularly in patients with functional thyroid autonomy. The present study was undertaken to evaluate whether contrast media applied during endoscopic retrograde cholangiopancreaticography (ERCP) may result in a significant increase of serum iodine levels and thus may be associated with the risk of iodine-induced hyperthyroidism. The courses of serum concentrations of total iodine and free iodide, as well as of urinary iodine excretion, were measured in 15 patients before and up to 21 days after ERCP. During ERCP, the non-ionic contrast medium iopamidol was instilled in amounts resulting in a total iodine load of 57.4 +/- 22.8 mmol (7.3 +/- 2.9 g). In all patients, ERCP resulted in a highly significant increase in serum levels of total iodine from 0.8 +/- 0.5 to 85.2 +/- 116.9 mumol/l 4 h after application of the contrast agent. In parallel, serum iodide levels were raised from 0.06 +/- 0.04 to 5.42 +/- 6.09 mumol/l and urinary iodine excretion from 71.1 +/- 35.7 mumol/mol creatinine to 621,620.9 +/- 636,492.2 mumol/mol creatinine. Peak concentrations of serum iodine are well related to the total amount of iodine applied (p < 0.05). During follow-up, iodine levels returned to pre-exposure levels within 2-3 weeks. Levels of thyrotropin, free thyroxine, and free triiodothyronine remained unchanged during the follow-up period. In conclusion, endoscopic application of iodinated contrast agents during ERCP leads to significant increases of serum levels of total iodine and free iodide and of urinary iodine excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Iodine supplementation in children receiving long-term parenteral nutrition

In 18 children receiving long-term total parenteral nutrition (TPN) without iodide supplements, thyroid function test results were normal but serum iodide levels were greater than in control subjects (p less than 0.01). Iodine contamination of TPN solutions and fat emulsions accounted for only half of the recommended parenteral intake. Skin absorption of topical iodinated disinfectant may explain the adequate, if not excessive, iodine intake. We conclude that iodine is an unnecessary supplement in TPN solutions.

Iodide‐induced hypothyroidism in patients after thyroid resection

The purpose of this investigation was to determine whether an intrinsic defect in thyroid hormone production is required for the development of iodide-induced hypothyroidism or does it also develop in TSH-stimulated normal thyroid tissue. To answer this question, we studied the response to iodine administration (180 mg iodide daily for 3-4 months) in eight euthyroid patients who had had partial thyroidectomies 2 months to 10 years previously for benign thyroid nodules, and in three euthyroid control subjects. In all 11 euthyroid patients, basal serum TSH concentrations increased during iodide administration. In six of the eight patients who had previous thyroid operations and in two of the three control patients, basal serum TSH concentrations increased into the abnormal range (greater than 6 U ml-1). Increased serum TSH concentrations were noted as early as 1 week after potassium iodide had been started and the increased levels persisted during the period of iodide administration. Although basal values for serum TSH concentration were initially within the normal range, those patients with highest basal serum TSH values developed the greatest increase in TSH in response to potassium iodine. Among the eight patients treated by partial thyroidectomy, serum T4 concentrations decreased in five, serum T3 concentration decreased in three and all five developed mild symptoms of hypothyroidism while receiving iodide. Serum T4 concentrations also decreased slightly in two of the three control patients. Serum total iodine levels increased from 7.0 +/- 0.5 to 315.7 +/- 108.6 g dl-1 (mean-+/- standard error) during potassium iodide administration, but there was no correlation between the level of serum iodide concentration achieved and inhibition of thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration of potassium iodide to normal volunteers does not increase killing ofSporothrix schenckiiby their neutrophils or monocytes

The mechanism by which iodide cures sporotrichosis was postulated to be an improvement in phagocyte-mediated killing of the causal fungus, Sporothrix schenckii. We found that both neutrophils and monocytes could readily kill the fungus and that killing could be blocked by adding inhibitors of oxidative metabolism. Iodide, administered to four volunteers for 1 week, raised their serum iodide level 213-fold but failed to improve killing of S. schenckii by their neutrophils or monocytes in a killing assay in vitro. Furthermore addition of iodide directly to neutrophils at concentrations as high as 100 microM did not augment killing. The mechanism by which iodide acts remains obscure.

The effects of topical povidone I solution on serum iodide levels and thyroid uptake of 131I in dogs.

Topical application of povidone I solution in dogs has been found to be effective in producing significant elevations in serum iodide concentrations within 2 h after application. Among dogs treated with this preparation 2 h before oral administration of 131I, significant thyroid blocking persisted for at least 72 h.

Effects of oral erythrosine (2′,4′,5′,7′-tetraiodofluorescein) on thyroid function in normal men

Erythrosine (Er), a tetraiodinated derivative of fluorescein, is a coloring agent widely used in foods, cosmetics, and pharmaceutical products. Because of its high iodine content and previous reports demonstrating an inhibitory effect of eythrosine on hepatic 5′-monodeiodination, we studied the effects of this compound on thyroid function and serum and urinary iodide concentrations in normal subjects. Thirty normal men, equally divided into three treatment groups, each received a 14-day course of oral Er in doses of 20, 60, or 200 mg/day. Serum thyroxine (T4), triiodothyronine (T3), reverse T3 (rT3), thyroid stimulating hormone (TSH), protein-bound iodide (PBI), and total iodide concentrations, serum T3-charcoal uptake, and 24-hour urinary iodide excretion were measured on Days 1, 8, and 15. Thyrotropin-releasing hormone (TRH) tests were performed on Days 1 and 15. There were no significant changes in serum T4, T3, rT3, and T3-charcoal uptake values at any dose. In men receiving 200 mg Er/day, the mean basal serum TSH concentration increased significantly from 1.7 ± 0.1 (SE) on Day 1 to 2.2 ± 0.1 μU/ml on Day 15 ( p < 0.05), and the mean peak TSH increment after TRH increased from 6.3 ± 0.5 to 10.5 ± 1.0 μU/ml ( p < 0.05). There were no significant changes in basal or peak TSH responses in the men receiving 20 or 60 mg Er/day. Significant dose-related increases in serum total iodide and PBI concentrations occurred during all three doses, and significant dose-related increases in urinary iodide excretion occurred during the 60 and 200 mg/day Er doses. These data suggest that the increase in TSH secretion induced by Er was related to the antithyroid effect of increased serum iodide concentrations, rather than a direct effect of Er on thyroid hormone secretion or peripheral metabolism.

Effect of variations in acute and chronic iodine intake on the accumulation and metabolism of [ 35S]propylthiouracil by the rat thyroid gland

Studies were performed to ascertain the effect of varying levels of chronic iodine intake and varying doses of iodide [0.002–100 μmoles KI/100 g body weight (BW)] given acutely on the rat thyroid metabolism of [ 35S]PTU (8.76 μmoles/kg BW). With variations in both acute and chronic iodine intake, as much as four-fold changes in the thyroid content of total 35S and unchanged [ 35S]PTU were observed. In the low, normal and high chronic iodine intake groups increasing doses of iodide given acutely produced a biphasic response in the thyroid accumulation of total 35S and unchanged [ 35S]PTU. In each of the three chronic iodine intake groups, increasing iodide doses up to 0.1 μmoles/100 g BW were associated with an increase in total 35S and unchanged [ 35S]PTU. At this level of acute iodide dosage, the increase averaged 45% (P < 0.01). Following acute iodide doses greater than 0.1 and up to 5.0 μmoles/100 g BW, the mean total 35S and unchanged [ 35S]PTU decreased to levels significantly (P < 0.001) lower than those at the peaks. Greater doses of iodide (up to 100 μmoles/100 g BW) produced no consistent further change in the thyroid content of total 35S or unchanged [ 35S]PTU. Irrespective of the acute iodide dose, the higher the level of chronic iodide intake, the higher the thyroid accumulation of total 35S and the lower the overall mean percentage of total 35S present as unchanged [ 35S]PTU. As would have been expected, increasing acute doses of iodide were associated with progressive decreases in thyroid: serum iodide concentration gradients, and the dose of acute iodide required to induce an acute Wolff-Chaikoff effect was greater the higher the level of chronic iodine intake. No correlation was evident, however, between the effects of acute doses of iodide on aspects of intrathyroid iodine metabolism and their effect on the thyroid metabolism of [ 35S]PTU.

Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities.

Disturbances in thyroid function and a high prevalence of goiter develop in patients on chronic hemodialysis. This study shows that in patients on dialysis, mean serum thyroxine and triiodothyronine levels are lower than normal. Patients with chronic renal failure not on dialysis, have mean serum thyroxine levels similar to normal subjects and low mean serum triiodothyronine levels. However, both serum thyroxine and triiodothyronine concentrations decrease as the renal failure worsens. In addition, both groups of patients with renal failure have a decreased serum thyroxine response to oxogenous thyrotrophin and a diminished serum thyrotrophin response to thyrotrophin-releasing hormone. These data suggest the presence of an intrathyroidal and an hypophyseal defect in uremic patients. Although serum iodide concentrations are elevated, there is no correlation between the level of serum iodide and the degree of renal failure. Therefore, we have no direct evidence that iodide excess is responsible for the abnormalities observed.

Removal of iodinated contrast material by peritoneal dialysis.

Acute renal failure following administration of radiographic contrast material is being reported with increasing frequency. In this study the clearance and extraction of iodinated contrast material by peritoneal dialysis was determined in a patient who became anuric following drip infusion pyelography. During 64 h of dialysis the serum iodide concentration decreased by a factor of 10, the peritoneal clearance of iodide was 12.1 ml/min, and 56% of the administered iodide was removed. These results suggest that contrast materials can be removed by dialysis if nephrotoxicity develops.