Serum Inorganic Iodide Research Articles

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.

Two-day inhalation toxicity study of methyl iodide in the rat

The effects of inhaled methyl iodide (MeI) on clinical pathology parameters, glutathione (GSH) tissue levels, serum thyroid hormone and inorganic iodide concentrations, S-methylcysteine hemoglobin concentrations, and liver UDP-glucuronyltransferase activity were studied in the rat. Male rats were exposed by whole-body inhalation to 0, 25, or 100 ppm MeI, 6 h/day for up to 2 days. Serum cholesterol concentrations (both high-density lipoprotein [HDL] and low-density lipoprotein [LDL] fractions) were increased and triglycerides were decreased at both exposure levels. Serum thyroid-stimulating hormone (TSH) concentrations were increased at 25 and 100 ppm, and serum triiodothyronine (T3) and thyroxine (T4) concentrations were decreased at 100 ppm. There was no change in either reverse triiodothyronine (rT3) or UDP-glucuronyltransferase activity at either exposure level. A dose- and time-dependent reduction in GSH levels in blood, kidney, liver, and nasal tissue was observed, with the greatest reduction in nasal tissue (olfactory and respiratory epithelium). MeI exposure also resulted in a substantial dose- and time-dependent increase in both serum inorganic iodide and red blood cell S-methylcysteine hemoglobin adducts. These results indicate that following inhalation exposure, MeI is rapidly metabolized in blood and tissue of rats, resulting in methylation products and release of inorganic iodide.

Thyroid function in patients with chronic renal failure

Chronic renal failure affects thyroid function in multiple ways, including low circulating thyroid hormone concentration, altered peripheral hormone metabolism, disturbed binding to carrier proteins, possible reduction in tissue thyroid hormone content, and increased iodine store in thyroid glands. Both plasma triiodothyronine (T3) and thyroxine (T4) are reduced. The low serum T3 is not due to increased T3 degradation or to decreased thyroidal T3 secretion but is a result of impaired extrathyroidal T4 to T3 conversion. The reduction in T4 is attributed to the presence of circulating inhibitors, which impair binding of T4 to thyroxine-binding globulin. Despite decreased circulating T4 and T3, thyroid-stimulating hormone (TSH) is not elevated. This absence of TSH elevation is not due to dysfunction of the hypothalamo-pituitary axis, because truly hypothyroid renal failure patients can mount a high TSH response. Thyroid hormone losses during hemodialysis and peritoneal dialysis are trivial and do not require replacement. Serum inorganic iodide and thyroidal iodine content are increased in renal failure patients, and thyroid gland enlargement is frequently encountered. Experiments performed to correct the low serum T3 level by administration of small doses of LT3 to renal failure patients resulted in lesser nitrogen balance, greater leucine flux, and protein degradation. We speculate that the low thyroid state in uremia serves to defend against protein wasting and that misguided attempts to replete thyroid hormone stores may worsen protein malnutrition. © 2001 by the National Kidney Foundation, Inc.

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.

Serum Inorganic Iodide Determined by Paired-Ion Reversed-Phase Hplc with Electrochemical Detection

We propose an automated method for the analysis of serum inorganic iodide (SII), using paired-ion reversed phase HPLC with electrochemical detection and a silver working electrode. Assay conditions include a flow rate of 1.0 mL/min and an operating potential of 0.10 V. The retention time for iodide is 5.3 min. Sample preparation consists in protein removal by ultrafiltration and concentration of the ultrafiltrate, because of the very low levels of SII, especially in iodine deficient areas. Ultrafiltration separation is achieved by pouring 2mL of a serum sample into a filter cup (membrane cutoff: 5kD) and then using a centrifugal force of 14000G over 90 min. A 1200μL aliquot of the ultrafiltrate is concentrated by a factor of 10 to a volume of 120μL in a centrifugal vacuum concentrator (Speed-Vac). A 100μL aliquot of the concentrate is injected into the HPLC. Due to concentration the detection threshold (signal-to-noise ratio of 3) could be lowered to 0.004μmol/L. The recovery of iodide during concentration of the ultrafiltrate tested with 123I was 102.2%. The within and between-run precision (CV) for a serum sample with 0.04μmol/L are 1.9% and 4.2%, respectively. For comparison with a standard method based on the isotope dilution principle serum samples from 26 patients who underwent thyroid scintigraphy with 123I were measured by both HPLC(y) and the standard technique(x). The data obtained show a high correlation (r=0.99; y=0.94x + 0.007; Syx=0.0179). Levels of SII typical of an iodine deficient area are measured in sera from 27 patients with low urinary iodine excretion (44μmol/molCrea): SII=0.023 μmol/L (mean); range: 0.01–0.036μmol/L.

Thyroid adaptation to chronic tetraglycine hydroperiodide water purification tablet use.

Tetraglycine hydroperiodide tablets purify water by liberating 8 mg free iodine/tablet. The effects of ingesting four tablets daily for 3 months on thyroid size, function, and radioactive iodine uptake were studied prospectively in eight healthy volunteers. Serum inorganic iodide increased from 2.7 to approximately 100 micrograms/dL. Urinary iodide excretion rose 150-fold from a pretreatment mean of 0.276 to 40 mg/day. Radioactive iodine uptake was less than 2% after 7 days and remained below 2% in all subjects at 90 days. Mean serum T4 and T3 declined after 7 days. T4 remained below baseline, whereas T3 had recovered by the end of the treatment period. Serum TSH and the TSH response to TRH rose significantly after 7 days and remained elevated at 3 months. The average thyroid volume, determined by ultrasound, increased by 37%. Neither hyperthyroidism nor hypothyroidism was observed. The mean thyroid volume in seven subjects available for repeat determinations an average of 7.1 months after the study was not different from the baseline value. In normal subjects, a reversible TSH-dependent thyroid enlargement occurs in response to the iodine load from daily use of tetraglycine hydroperiodide water purification tablets.

Urinary iodide excretion in Japanese people and thyroid dysfunction

In order to assess the Japanese dietary iodine intake, we examined the urinary iodine excretion of those on an ordinary Japanese diet chosen at random and observed whether the thyroid function might affect the amounts of urinary iodine excretion. The subjects consisted of cases of untreated hypothyroidism and chronic thyroiditis (CT) and euthyroid controls who were healthy people or had non-thyroidal disorders such as diabetes mellitus or hypertension. Eight cases of hypothyroidism were composed of 3 cases of secondary hypothyroidism with empty sella syndrome and 5 cases of primary hypothyroidism and 32 patients with CT have been maintained in euthyroid states with T4 medication. We selected 32 cases of sex and age-matched healthy people as controls. The mean levels of excreted urinary iodine were 465.6 micrograms/day in the healthy controls and 471.8 micrograms/day in patients with CT, respectively. Urinary iodine excretion was significantly correlated to serum inorganic iodide in both controls and CT patients, of which correlation coefficients were +0.35 and +0.5, respectively. Urinary iodine and serum inorganic iodide ratios (U/S) in hypothyroidism were significantly (p less than 0.05) depressed compared with those in CT. The present study indicated that recent Japanese dietary iodine intake was estimated to be approximately 470 micrograms/day and that the urinary iodine excretion would be influenced not only by iodine intake but also by thyroid function.

The functional outcome of patients with subacute thyroiditis

Whether with the passage of time subacute thyroiditis leads to hypothyroidism remains to be determined. Therefore, we evaluated the thyroid function including TRH test of 66 patients with a previous history of subacute thyroiditis and age-matched control subjects with special reference to the measurement of inorganic iodide. The patients were divided into 3 groups according to time lapse since the occurrence. Group 1 consisted of 24 cases followed up for 4 to 24 months. Sixteen cases in group 2 had their courses from 2 to 5 years, and group 3 was composed of 26 cases over the past 5 to 30 years. We selected 169 subjects without history of subacute thyroiditis and divided them into three control groups matched for age, each corresponding to the patient groups (group 1a, 2b and 3c, respectively). 41.7% and 29.2% of cases in group 1 had high basal levels of serum TSH (greater than 3.6 microU/ml) and delta TSH (the increment of TSH after TRH, greater than 46.8 microU/ml). In group 2, levels of serum T3 and T4 returned to normal ranges. However, in group 3, significant higher elevations in TSH and delta TSH than those in group 3c were observed, and the T4, FT4, T3 and FT3 levels were lower than those of group 3c (p less than 0.01 and p less than 0.05, respectively). 42.3% of cases in group 3 showed high TSH, and there were 4 cases with clinical hypothyroidism. Among the cases studied, a significant negative correlation (p less than 0.01) between levels of TSH and T4 was observed, while a correlation between TSH and delta TSH was positive (p less than 0.001). High levels of serum inorganic iodide were observed in 6.1% of cases and a correlation between inorganic iodide and TSH was significantly positive (p less than 0.01) not only in patients with subacute thyroiditis, but also in the control subjects. Antithyroid autoantibodies were detected in 42.4% of all the cases with subacute thyroiditis and also in 45.6% of all the controls. In group 3, MCHA was detected in 64.5% of the cases, and the frequency was higher than that of group 3c as well as that of 25% in group 2 (p less than 0.01), respectively. In 15.4% of the cases in group 3, the titers of MCHA were more than 40(2), and the titers of MCHA were significantly higher in patients with a long-term period after the onset of subacute thyroiditis than those with a short-term period.(ABSTRACT TRUNCATED AT 400 WORDS)

The Effects on the Thyroid Gland of Soybeans Administered Experimentally in Healthy Subjects

To elucidate whether soybeans would suppress the thyroid function in healthy adults, we selected 37 subjects who had never had goiters or serum antithyroid antibodies. They were given 30g of soybeans everyday and were divided into 3 groups subject to age and duration of soybean administration. In group 1, 20 subjects were given soybeans for 1 month. Groups 2 and 3 were composed of 7 younger subjects (mean 29 y.o.) and 10 elder subjects (mean 61 y.o.) respectively, and the subjects belonging to these groups received soybeans for 3 months. The Wilcoxon-test and t-test were used in the statistical analyses. In all groups, the various parameters of serum thyroid hormones remained unchanged by taking soybeans, however TSH levels rose significantly although they stayed within normal ranges. The TSH response after TRH stimulation in group 3 revealed a more significant increase than that in group 2, although inorganic iodide levels were lowered during the administration of the soybeans. We have not obtained any significant correlation between serum inorganic iodide and TSH. Hypometabolic symptoms (malaise, constipation, sleepiness) and goiters appeared in half the subjects in groups 2 and 3 after taking soybeans for 3 months, but they disappeared 1 month after the cessation of soybean ingestion. These findings suggested that excessive soybean ingestion for a certain duration might suppress thyroid function and cause goiters in healthy people, especially elderly subjects.

Effect of mouth rinsing with two polyvinylpyrrolidone-iodine mixtures on iodine absorption and thyroid function.

A prospective study was conducted to investigate the effect of long term therapy with two iodine-containing mouth rinses on thyroid function. Two groups of subjects were treated daily for 6 months with either a 5% polyvinylpyrrolidone (PVPI)-1.5% H2O2 mixture (Perimed) or a 5% PVPI-water mixture. Thyroid function studies, serum iodine concentrations, and urinary iodine excretion were measured before treatment, at 6-week intervals during the 6-month treatment period, and 3 weeks after the last treatment. There was evidence of significant iodine absorption (elevated serum total iodine and inorganic iodide concentrations and urinary iodine excretion) from daily use of both Perimed and the PVPI-water mixture. Serum T3 and T4 concentrations and the free T4 index did not change. There was a small significant rise in serum TSH concentrations during mouth rinse therapy, but all values remained within the normal range. This small increase in serum TSH is a normal adaptive response to the antithyroid effect of increased iodine intake and accounts for the maintenance of normal serum T4 and T3 concentrations. While daily use of these iodine-containing mouth rinses does result in significant iodine absorption, there is no evidence for the development of thyroid dysfunction during a 6-month course of therapy.

Suppression of thyroidal iodine uptake after indocyanine green.

The 24-hr thyroidal uptake of radioiodine (RAIU) is suppressed following administration of indocyanine green, a dye commonly used to measure cardiac output. Studies were conducted in 21 normal subjects and 6 patients with hyperthyroidism to determine the mechanism responsible for this suppression and to evaluate its clinical significance. Analysis of the dye revealed that each 25 mg dose contained 1.274 ± 0.68 mg of inorganic iodide. Administration of indocyanine green had no effect on the protein-bound iodide concentration but significantly increased the serum inorganic iodide concentration of both groups. The most striking effect of indocyanine green was suppression of the RAIU. In normal subjects the mean decrease in RAIU was 6% but only 8 of the 21 subjects had a decrease of 5% or greater. In contrast, the mean decrease in RAIU of patients with hyperthyroidism was 33% and 4 of the 6 patients had normal values for RAIU after administration of the dye.

Removal of Inorganic Iodide in the Automated Serum Protein-Bound Iodine Determination

Abstract Values for serum protein-bound iodine (PBI) concentration obtained by the AutoAnalyzer method are too high because of the failure of the batch (Technicon) process to completely remove inorganic iodide. The Technicon method removes about 98% of the inorganic iodide; this incomplete adsorption of inorganic iodide would give falsely elevated PBI values in serums with high iodide concentrations. A rapid, economical method for removing serum inorganic iodide to the extent of 99.8% by a single pass of serum through a small column packed with an anion-exchange resin is described. Using Dowex-1 x 8, 20-50 mesh, 2 ml. of serum is filtered in 30 sec. directly into an AutoAnalyzer sample cup. Filtration through the column eliminates all possibility of clogging the sample probe with either resin beads or serum clots. The column method requires a little less serum than the batch process.

Reduction of Thyroid Irradiation From 131I by Potassium Iodide

The prophylactic administration of 100 to 200 mg of potassium iodide in anticipation of radioactive iodine exposure will largely prevent uptake by the thyroid gland, thereby reducing the irradiation dose delivered by more than 98%. The same amount given at intervals after 131 I absorption is progressively less effective, but still reduces uptake to less than half after a delay of three hours. The suppressive effect of one dose is of short duration and daily readministration of the agent is required for prolonged protection. The extent of uptake blockade may be estimated by measuring serum inorganic iodide; concentrations of greater than 10μg /100 cc correlate with marked uptake arrest. Toxicity is negligible for a single ingestion, as is required in this temporary measure for the reduction of the immediate thyroid irradiation hazard, but the drug must be avoided by those allergic to it.

The effects of varying amounts of stable iodide on the function of the human thyroid.

ABSTRACT The effect of addition of varying amounts of stable iodine to doses of radioiodine was studied in 64 euthyroid persons and in 46 with disturbed thyroid function. The addition of 1 to 2 mg. of stable iodine, as potassium iodide, reduced the uptake of radioiodine to a significantly greater degree in patients with Graves' disease than in euthyroid patients. The difference in response to the added load of iodine suggests that a relatively brief and precise test of thyroid function, an “iodide inhibition test,” may be evolved from these studies. The concentration of serum inorganic iodide was found, by indirect means, to be considerably less than 0.5 μg. per 100 ml. in most instances, regardless of thyroid function. Calculation of the rate of accumulation of iodine by the thyroid revealed that, when the serum iodide level was raised to about 6 μg. per 100 ml., the normally functioning thyroid gland accepted the load and accumulated more than ten times the normal amount of stable iodide per unit time. ...

The effect of iodide on the release of thyroid hormone in hyperthyroidism.

The mechanism whereby the iodide ion beneficially affects the syndrome of hyperthyroidism remains unclear. Wolff and Chaikoff have shown that in the rat, elevation of the serum inorganic iodide concentration to approximately 30 micrograms per 100 ml. inhibits the synthesis of thyroid hormone (1). This effect, however, is transient. Stanley has presented evidence that in man, when the serum inorganic iodide concentration exceeds 6 micrograms per 100 ml. there is partial inhibition of organic binding of iodine in the thyroid gland (2). These experiments suggest that iodine exerts its effect by slowing the rate of synthesis of thyroid hormone. A different process by which iodide may affect hyperthyroidism is intimated by the in vitro studies of Albert and associates (3).

Protein-bound iodine levels in normal and in diabetic children.

THE DEVELOPMENT of reliable semimicroanalytic procedures has permitted more precise studies of the circulating iodine fractions.¹As a consequence, much of the confusion resulting from methodologic inadequacies and from the use of blood instead of serum samples has been eliminated. In brief, applications of these methods have revealed that the level of serum inorganic iodide in healthy adults varies, as might be expected, with the intake of this halide, but with an ordinary diet it only infrequently exceeds 1 γ per 100 ml.²The major fraction, called protein-bound or serum-precipitable iodine, ranges in euthyroid adults between 4 and 8 γ per 100 ml.,³remains quite constant in any one person from week to week.⁴and from the point of view of solubility, behaves like thyroxine.⁵Thyrotoxicosis⁶and uncomplicated pregnancy⁷are characterized by elevations of both protein-bound iodine and of thyroxine.⁸Hypothyroidism, or