Iodide Exposure Research Articles

Repeated potassium iodide exposure during pregnancy impairs progeny’s brain development

Protracted radioiodine release may require repeated intake of potassium iodide (KI) to protect thyroid gland. It is well established that iodine excess inhibits transiently the thyroid function. As developing fetus depends on maternal thyroid hormones (TH) supply, more knowledge is needed about the plausible effects that repeated KI intake can cause in this sensitive population, especially that even subtle variation of maternal thyroid function may have persistent consequences on progeny brain processing. The aim of this study is to assess the consequences of repeated intake of KI during pregnancy on the progeny's thyroid function and brain development. To do so pregnant Wistar rats received KI over eight days, and then thirty days after the weaning, male progeny was subjected to behavior test. Pituitary and thyroid hormones level, anti-thyroid antibodies level, organs morphology, gene expression and global DNA methylation were assessed. Thirty days after the weaning, KI-exposed male progeny showed an uncommon hormonal status, characterized by a decrease of both thyroid-stimulating hormone (−28%) and free thyroxine (−7%) levels. Motor coordination was altered in KI-exposed male progeny. At the cerebellar level, we observed a decrease of mRNA expression of DCX (−42%) and RC3 (−85%); on the other hand, at the cortical level, mRNA expression of MBP (+71%), MOBP (+90%) and Kcna1 (+42%) was increased. To conclude, repeated KI prophylaxis is not adequate during pregnancy since it led to long-term irreversible neurotoxicity in the male progeny.

Iodine in excess in the alterations of carbohydrate and lipid metabolic pattern as well as histomorphometric changes in associated organs.

Background Iodine is a nonpareil constituent of thyroid hormones (THs) and a prime regulator of thyroid gland functioning. Although essential at recommended levels for the prevention of iodine deficiency disorders (IDDs), exposure to excess iodine reportedly causes hypothyroidism, hyperthyroidism, and several other emerging deleterious impacts. The objective of the present study is to explore the influence of excess iodide exposure on carbohydrate and lipid metabolism along with the histoarchitecture of certain associated organs such as the pancreas, liver, kidney, and skeletal and cardiac muscle because information on those aspects was found to be scanty. Methods Twelve rats were taken, six were fed with iodine through gavage at a dose of 3.5 mg potassium iodide (KI)/100-g body weight, which corresponded to 500 times of the physiological daily dosage of iodide for a period of 60 days, while the other six formed the control group. Results KI-treated rats presented high body weight and urinary iodine with low TH levels, suggesting a primary thyroid dysfunction. There was an increase in blood glucose, cholesterol, triglycerides, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), while high density lipoprotein (HDL) levels decreased. Tissue glycogen content in the liver and skeletal muscle was decreased and was increased in the heart and kidney. Histological sections of the pancreas showed a complete disruption with hardly recognizable histoarchistructure. Treated liver sections displayed the broadened central vein with degenerated hepatocytes, while skeletal muscle sections showed dissolution of muscle fibre cells linked with loss of glycogen from these organs. Histological changes in the heart include features similar to those of a fatty heart with cardiac muscles mutilation, while that of the kidney shows an increase in glomerular tuft size and Bowman's space expansion with general deterioration. Conclusions It may thus be concluded that excess iodine exposure for a long duration causes the development of a biochemical state of hypothyroidism. The developed hypothyroidism was found responsible for the hyperglycaemic and hypercholestromic status evident by high blood glucose and cholesterol levels and the depletion of glycogen at its storage sites in the liver and skeletal muscle but the extra deposition in the cardiac muscle and kidney; histomicrophotographs showed severe destruction of the pancreatic structure. All these alterations are conducive for the pathogenesis of cardiovascular and kidney diseases.

Supplemental Iodide for Preterm Infants and Developmental Outcomes at 2 Years: An RCT.

The recommendation for enteral iodide intake for preterm infants is 30 to 40 μg/kg per day and 1 μg/kg per day for parenteral intake. Preterm infants are vulnerable to iodide insufficiency and thyroid dysfunction. The hypothesis tested whether, compared with placebo, iodide supplementation of preterm infants improves neurodevelopment. A randomized controlled trial of iodide supplementation versus placebo in infants <31 weeks' gestation. Trial solutions (sodium iodide or sodium chloride; dose 30 μg/kg per day) were given within 42 hours of birth to the equivalent of 34 weeks' gestation. The only exclusion criterion was maternal iodide exposure during pregnancy or delivery. Whole blood levels of thyroxine, thyrotropin, and thyroid-binding globulin were measured on 4 specific postnatal days. The primary outcome was neurodevelopmental status at 2 years of age, measured by using the Bayley Scales of Infant Development-III. The primary analyses are by intention-to-treat, and data are presented also for survivors. One thousand two hundred seventy-three infants (637 intervention, 636 placebo) were recruited from 21 UK neonatal units. One hundred thirty-one infants died, and neurodevelopmental assessments were undertaken in 498 iodide and 499 placebo-supplemented infants. There were no significant differences between the intervention and placebo groups in the primary outcome: mean difference cognitive score, -0.34, 95% confidence interval (CI) -2.57 to 1.89; motor composite score, 0.21, 95% CI -2.23 to 2.65; and language composite score, -0.05, 95% CI -2.48 to 2.39. There was evidence of weak interaction between iodide supplementation and hypothyroxinemic status in the language composite score and 1 subtest score. Overall iodide supplementation provided no benefit to neurodevelopment measured at 2 years of age.

Genes Outside the Major Histocompatibility Complex Locus Are Linked to the Development of Thyroid Autoantibodies and Thyroiditis in NOD.H2h4 Mice.

Thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) develop spontaneously in NOD.H2h4 mice, a phenotype enhanced by dietary iodine. NOD.H2h4 mice were derived by introducing the major histocompatibility class (MHC) molecule I-Ak from B10.A(4R) mice to nonobese diabetic (NOD) mice. Apart from I-Ak, the genes responsible for the NOD.H2h4 phenotype are unknown. Extending serendipitous observations from crossing BALB/c to NOD.H2h4 mice, thyroid autoimmunity was investigated in both genders of the F1, F2, and the second-generation backcross of F1 to NOD.H2h4 (N2). Medium-density linkage analysis was performed on thyroid autoimmunity traits in F2 and N2 progeny. TgAb develop before TPOAb and were measured after 8 and 16 weeks of iodide exposure; TPOAb and thyroiditis were studied at 16 weeks. TgAb, TPOAb, and thyroiditis, absent in BALB/c and F1 mice, developed in most NOD.H2h4 and in more N2 than F2 progeny. No linkages were observed in F2 progeny, probably because of the small number of autoantibody-positive mice. In N2 progeny (equal numbers of males and females), a chromosome 17 locus is linked to thyroiditis and TgAb and is suggestively linked to TPOAb. This locus includes MHC region genes from B10.A(4R) mice (such as I-Ak and Tnf, the latter involved in thyrocyte apoptosis) and genes from NOD mice such as Satb1, which most likely plays a role in immune tolerance. In conclusion, MHC and non-MHC genes, encoded within the chromosome 17 locus from both B10.A(4R) and NOD strains, are most likely responsible for the Hashimoto disease-like phenotype of NOD.H2h4 mice.

Iodide excess regulates its own efflux: a possible involvement of pendrin.

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

Association of Prenatal Perchlorate, Thiocyanate, Nitrate and Iodide Exposure with Birth Weight, Length, and Head Circumference

Background: We previously found maternal urinary perchlorate, thiocyanate, and nitrate to be positively correlated with levels in amniotic fluid, which may restrict fetal growth by inhibiting thyro...

Effect of early acute high concentrations of iodide exposure on mitochondrial superoxide production in FRTL cells

Excessive oxidative stress has been suggested as one of the underlying mechanisms in the development of thyroid cytotoxicity. Although the involvement of mitochondria has been hypothesized, the effect of early acute high concentrations of iodide on mitochondrial superoxide production remains largely unknown, especially within a 24h time frame. By using a novel fluorescent probe, MitoSOX Red, we demonstrated the concentration response and time-course response of KI-induced mitochondrial superoxide production in the Fischer rat thyroid cell line (FRTL). A strong increase of MitoSOX Red fluorescence intensity in FRTL cells can be seen at 2h following high concentrations of iodide exposure. Besides, we indicated that 6-propyl-2-thiouracil (PTU, 300μM), thyroid-stimulating hormone (TSH, 10mU/ml), and perchlorate (KClO4, 30μM) can inhibit excessive iodide-induced strong mitochondrial superoxide production; however, diethyldithiocarbamic acid (DETC, 2mM) can further increase excessive iodide-induced mitochondrial superoxide production. By using transmission electron microscopy (TEM), we noted accumulated myelinoid bodies with lipid droplets and numerous apoptotic nuclear bodies at 24h in FRTL cells. In addition, we demonstrated a significant decrease in cytochrome c (cyt c) content in the mitochondria by enzyme linked immunosorbent assay (ELISA), and DNA fragments and significant increases in lactate dehydrogenase (LDH) activity were detected. We propose a sequence of events mediated by a strong mitochondrial superoxide production at 2h, followed by lipid peroxidation, cell membrane damage with significant cyt c release, culminating in DNA fragmentation and apoptotic nuclear formation at 24h, which may partly contribute to the underlying mechanisms of early acute iodide excess.

Iodide-Induced Parotitis after Coronary Angiography

A 55-year-old woman with stable angina pectoris who had undergone elective coronary catheterization five years ago, no coronary artery disease had been reported at that time. Recent noninvasive stress testing was performed and the result was positive. Coronary angiography was repeated by using iodinated contrast medium. At catheterization, no angiographically significant coronary stenoses was found. About 36 hours after coronary angiography she presented to the emergency department for swelling of face and throat bilaterally. Her parotid glands were diffusely and symmetrically enlarged to twice the normal size and glands were firm and non-tender. This case had taken iodinated contrast medium before and she had the same symptoms. So she might be an example of recurrent parotitis caused by repeated iodide exposure. (Hong Kong j.emerg.med. 2011;18:421-423)

Acute methyl iodide exposure with delayed neuropsychiatric sequelae: Report of a case

Methyl iodide is a monohalomethane used as an analytic and organic chemistry reagent, as a methylating agent in organic chemical synthesis, and as a fumigant. In an acute exposure, methyl iodide is a pulmonary and dermal irritant. Chronic neurotoxicity has been reported in survivors of acute exposure. A review of the 11 case reports of methyl iodide poisoning in the medical literature of the 20th century found that six of the patients experienced a chronic neurological syndrome characterized primarily by delayed psychiatric, behavioral, and cognitive sequelae. The case patient experienced a massive exposure to methyl iodide with resulting life-threatening burns. During convalescence, various cognitive and behavioral deficits became apparent. The results of a comprehensive evaluation at our occupational toxicology clinic, which included sequential neuropsychometric testing, are described. The findings in the case patient may advance our understanding of the mechanisms and clinical manifestations of chronic neurotoxicity after exposure to methyl iodide.

The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health.

Several minerals and trace elements are essential for normal thyroid hormone metabolism, e.g., iodine, iron, selenium, and zinc. Coexisting deficiencies of these elements can impair thyroid function. Iron deficiency impairs thyroid hormone synthesis by reducing activity of heme-dependent thyroid peroxidase. Iron-deficiency anemia blunts and iron supplementation improves the efficacy of iodine supplementation. Combined selenium and iodine deficiency leads to myxedematous cretinism. The normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Among these selenoproteins are the glutathione peroxidase, deiodinase, and thioredoxine reductase families of enzymes. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland from damage by excessive iodide exposure. In regions of combined severe iodine and selenium deficiency, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid hormone economy may develop under conditions of special dietary regimens such as long-term total parenteral nutrition, phenylketonuria diet, cystic fibrosis, or may be the result of imbalanced nutrition in children, elderly people, or sick patients.

Evidence that the inhibitory effects of iodide on thyroid cell proliferation are due to arrest of the cell cycle at G0G1 and G2M phases.

The thyroid gland is unique in its ability to respond to ambient levels of iodine to autoregulate thyroid function and, possibly, thyroid cell proliferation. Although the inhibitory effects of iodide on thyroid cell proliferation have been previously reported, the exact mechanism and site of action of iodide on cellular proliferation events are poorly understood. Our initial experiments established the optimal cell plating density and timing to achieve exponential cell growth of FRTL5 thyroid cells, and subsequent studies using flow cytometric DNA analysis established the normal cell cycle kinetics of FRTL5 thyroid cell proliferation. FRTL5 cells were then exposed to graded concentrations of sodium iodide to establish whether the inhibitory effects of iodide are mediated through specific cell cycle events. We observed that increasing concentrations of iodide inhibited FRTL5 thyroid cell proliferation. Analysis of the cell cycle revealed two specific effects of iodide on cell cycle kinetics. The first was an arrest of cells in G0G1, evidenced by an accumulation of cells in this phase and a concomitant reduction in the percentage of cells in the S-phase. The second was an arrest of cells in the G2M phase of the cycle. G0G1 and G2M arrest occurred within 24 h and then reached a plateau. Iodide exposure did not increase the number of cells undergoing necrosis. The addition of methimazole at two concentrations (0.2 and 2 mM) to cells exposed to 100 mM NaI prevented the accumulation of cells in G2M, but did not abolish the accumulation of cells in G0G1 or the reduction in cell number. These results indicate that the inhibitory effects of iodide on FRTL5 thyroid cell proliferation are mediated by its action at two critical regulating points of the cell cycle, G0G1 and G2M. It appears that organified iodine may mediate the cell cycle arrest in the G2M phase, whereas inorganic iodide may be responsible for the inhibitory effects at G0G1.