Bilateral retinal toxicity as a result of poisoning with pure iodine.

Iodine is an essential mineral that is necessary for the synthesis of thyroid hormones, which can cause many diseases in the body. The application of adding potassium iodate to table salts started in Turkey in 1998. High doses of iodate cause retinal toxicity, leading to significant vision loss. A 42-year-old paranoid schizophrenic patient who attempted suicide with pure iodine was admitted with bilateral vision loss. Widespread retinal pigment epithelium (RPE), ellipsoid zone (EZ) and interdigitation zone (IZ) damage were present in the optical coherence tomography (OCT) assessment. Fundus autofluorescence (FAF) findings, which included hypoautofluorescence areas that supported this condition, were also found. In conclusion, iodate in high doses is toxic on RPE, EZ and IZ. This situation could be irreversible depending on the dose.

Iodine intake as a risk factor for BRAF mutations in papillary thyroid cancer patients from an iodine-replete area.

PURPOSE: Both deficient and excessive iodine intake leads to thyroid disease, which shows U-shaped curves. Our previous study showed that a relatively low [urinary iodine concentration (UIC) <300 µg/L] and extremely excessive (UIC ≥ 2500 µg/L) iodine intake were associated with thyroid cancer in Korea, an iodine-replete area. Papillary thyroid cancer (PTC) accounts for more than 97 % of thyroid cancer and 80% or more PTC cases harbor the BRAF mutation in Korea. We aimed to investigate the relationship between iodine intake and the prevalence of the BRAF mutation in PTC in Korea. METHODS: UIC was measured by inductively coupled plasma mass spectrometry. The BRAF mutation was detected using both allele-specific polymerase chain reaction and mutant enrichment with 3'-modified oligonucleotide sequencing. Risk factors for the occurrence of BRAF mutations in PTC were evaluated using multivariate logistic regression models. RESULTS: The median UIC in all patients with PTC was 287 µg/L (range from 7 to 7, 426 µg/L). Nearly half of the patients (102/215, 47%) belonged to the excessive iodine intake category (UIC ≥ 300 µg/L) according to the WHO iodine recommendations. The frequency of BRAF mutations was lowest in the 300-499 µg/L UIC group; it was significantly different compared to the relatively low (UIC < 300 µg/L) and more than excessive (UIC ≥ 500 µg/L) iodine intake groups. UIC was an independent predictor for BRAF mutations in PTC. The multivariate-adjusted odds ratios (95% confidence intervals) in the relatively low and more than excessive iodine intake groups for the BRAF mutation were 4.761 (1.764-12.850) and 6.240 (2.080-18.726), respectively, compared to the 300-499 µg/L UIC group. CONCLUSION: Relatively low iodine intake and more than excessive iodine intake seem to be significant risk factors for the occurrence of BRAF mutations in the thyroid and, therefore, may be risk factors for the development of PTC in an iodine-replete area.

Underlying Mechanisms of Pituitary-Thyroid Axis Function Disruption by Chronic Iodine Excess in Rats.

BACKGROUND: Iodine is essential for thyroid hormone synthesis and is an important regulator of thyroid function. Chronic iodine deficiency leads to hypothyroidism, but iodine excess also impairs thyroid function causing hyperthyroidism, hypothyroidism, and/or thyroiditis. This study aimed to investigate the underlying mechanisms by which exposure to chronic iodine excess impairs pituitary-thyroid axis function. METHODS: Male Wistar rats were treated for two months with NaI (0.05% and 0.005%) or NaI+NaClO4 (0.05%) dissolved in drinking water. Hormone levels, gene expression, and thyroid morphology were analyzed later. RESULTS: NaI-treated rats presented high levels of iodine in urine, increased serum thyrotropin levels, slightly decreased serum thyroxine/triiodothyronine levels, and a decreased expression of the sodium-iodide symporter, thyrotropin receptor, and thyroperoxidase mRNA and protein, suggesting a primary thyroid dysfunction. In contrast, thyroglobulin and pendrin mRNA and protein content were increased. Kidney and liver deiodinase type 1 mRNA expression was decreased in iodine-treated rats. Morphological studies showed larger thyroid follicles with higher amounts of colloid and increased amounts of connective tissue in the thyroid of iodine-treated animals. All these effects were prevented when perchlorate treatment was combined with iodine excess. CONCLUSIONS: The present data reinforce and add novel findings about the disruption of thyroid gland function and the compensatory action of increased thyrotropin levels in iodine-exposed animals. Moreover, they draw attention to the fact that iodine intake should be carefully monitored, since both deficient and excessive ingestion of this trace element may induce pituitary-thyroid axis dysfunction.

A low incidence of iodine-induced hyperthyroidism following administration of iodinated contrast in an iodine-deficient region.

OBJECTIVE: There are limited data on the incidence of iodinated contrast-induced thyrotoxicosis, particularly in iodine-deficient regions. The aim of this study was to determine the incidence of iodinated contrast-induced thyrotoxicosis and to determine whether thyrotoxicosis was more common in patients ≥70 years compared to those <70 years of age. DESIGN: A prospective study of adult patients undergoing an outpatient CT with iodinated contrast was performed. MEASUREMENTS: Thyroid function tests (TFTs) and urine iodine measurements were performed prior to the scan. TFTs were repeated at 4- and 8-weeks postscan. Changes in TFTs from baseline were analysed. RESULTS: A total of 102 patients were included in the final analysis. Overall, TSH levels dropped (P = 0·0002), and free T3 (FT3 ) levels increased (P = 0·04) between baseline and week 4 with normalization by week 8; however, these changes were not considered clinically significant. No significant differences in free T4 (FT4 ) occurred in the overall group (P = 0·82). There were no differences in TFTs between baseline and 4 or 8 weeks for those patients aged <70 compared to ≥70 years. Two patients developed new subnormal TSH values. Of these, one had a 90-mm follicular variant papillary thyroid carcinoma diagnosed while the other had a normal thyroid assessment and TSH spontaneously normalized by 12 weeks. CONCLUSIONS: Only 2% of patients developed subclinical hyperthyroidism following a standard dose of iodinated contrast for CT investigations. Given the low incidence of iodine-induced thyrotoxicosis, there is no indication for routine pre- and post-CT thyroid function testing in our region.

Subclinical Hypothyroidism and Elevated Thyroglobulin in Infants with Chronic Excess Iodine Intake.

BACKGROUND: Acute iodine excess in newborns can cause hypothyroidism, but there are limited data on the effects of iodine excess on thyroid function in older infants. The aim of this study was to measure the effects of chronic excess iodine intake on thyroid function in 6-24-month-old infants. METHODS: In this cross-sectional study, infants (n=696) in eastern Nepal were studied. Spot urine samples, venous blood samples, and household salt samples were collected, and urinary iodine concentration (UIC), serum free thyroxine (fT4), thyrotropin (TSH), thyroglobulin (Tg), and titrated household salt iodine concentration (SIC) were measured. Daily iodine intake was calculated from UIC based on estimates of urine volume at this age. RESULTS: Median (25th-75th percentile) household SIC was 89 (70-149) ppm, while national legislation stipulates a fortification level of 50 ppm. Median UIC was 407 (312-491) µg/L; 76% of infants had a UIC >300 µg/L, suggesting iodine excess. Calculated mean iodine intake in 12-24-month-old infants was 220 µg/day, exceeding the recommended safe upper limit for iodine at this age (200 µg/day). Among the infants, 15.8% had an elevated Tg, 7.4% had subclinical hypothyroidism, but <1% had overt hypothyroidism. UIC was not a significant predictor of thyroid function, thyroid hormones, or Tg. CONCLUSION: In 6-24-month-old infants exposed to excessive iodine intake, ∼7% have subclinical hypothyroidism but <1% have overt hypothyroidism. These findings suggest the thyroid in late infancy is already able to adapt to high iodine intakes and, in most cases, maintain euthyroidism.

Global iodine nutrition: Where do we stand in 2013?

BACKGROUND: Dietary iodine intake is required for the production of thyroid hormone. Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality. SUMMARY: In 1990, the United Nations World Summit for Children established the goal of eliminating iodine deficiency worldwide. Considerable progress has since been achieved, largely through programs of universal salt iodization. Approximately 70% of all households worldwide currently have access to adequately iodized salt. In 2013, as defined by a national or subnational median urinary iodine concentration of 100-299 µg/L in school-aged children, 111 countries have sufficient iodine intake. Thirty countries remain iodine-deficient; 9 are moderately deficient, 21 are mildly deficient, and none are currently considered severely iodine-deficient. Ten countries have excessive iodine intake. In North America, both the United States and Canada are generally iodine-sufficient, although recent data suggest pregnant U.S. women are mildly iodine-deficient. Emerging issues include discrepancies between urinary iodine status in pregnant women compared to school-aged children in some populations, the problem of re-emerging iodine deficiency in parts of the developed world, the importance of food industry use of iodized salt, regions of iodine excess, and the potential effects of initiatives to lower population sodium consumption on iodine intake. CONCLUSIONS: Although substantial progress has been made over the last several decades, iodine deficiency remains a significant health problem worldwide and affects both industrialized and developing nations. The ongoing monitoring of population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations, such as pregnant women and infants. There is also need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition. Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines.

Over-the-counter-drug-induced thyroid disorders.

OBJECTIVE: Excessive iodine ingestion may cause thyroid dysfunction. In this case series, we report four patients who developed significant thyroid dysfunction after ingesting over-the-counter (OTC) drugs containing large concentrations of iodine. METHODS: Four patients from a tertiary medical center are reported. RESULTS: Case 1 involved acute exacerbation of thyrotoxicosis induced by taking OTC Tri-iodine™ in a 35-year-old woman while still on methimazole therapy. Case 2 involved thyroid-extract-induced thyrotoxicosis following ingestion of Thyromine™, and was confirmed by laboratory studies and ¹³¹I thyroid uptake. Cases 3 and 4 involved severe, symptomatic hypothyroidism induced in 2 patients with underlying autoimmune thyroiditis (Hashimoto's disease) following ingestion of Iodoral™. In all cases, thyroid dysfunction resolved with appropriate management and discontinuation of the OTC drugs. CONCLUSION: These case reports demonstrate the significant risks associated with OTC preparations containing iodine in patients predisposed to thyroid dysfunction. There is no valid reason for taking high-dose OTC iodine supplements, which have been shown to cause harm and have no known benefit.

Acute hemolysis following iodine tincture ingestion.

Iodine tincture poisoning is uncommon regardless of its widespread use as an antiseptic in daily practice. Previously reported effects of iodine-containing antiseptic poisoning included topical irritation, corrosive effects, allergic response, and hepatic or renal injury, which mainly resulted from complications of topical use during surgical procedures. We herein reported an unusual case of severe hemolysis and acute renal failure following intentional ingestion of iodine tincture containing 60 mg/ml iodine and 40 mg/ml potassium iodide in 70% v/v ethanol. The patient completely recovered 8 weeks later after receiving supportive treatment, plasma exchange, and temporary hemodialysis.

Environmental exposures and autoimmune thyroid disease.

BACKGROUND: Environmental exposures, ranging from perchlorate in rocket fuel to polychlorinated biphenols, have been shown to influence thyroid function. Although most of these agents are associated with reduced thyroid hormone levels or impaired thyroid hormone action, a number of environmental exposures confer an increased risk of autoimmune thyroid disease. SUMMARY: Factors that increase autoimmune thyroid disease risk include radiation exposure, both from nuclear fallout and medical radiation, increased iodine intake, as well as several contaminants in the environment that influence the thyroid. Although approximately 70% of the risk for developing autoimmune thyroid disease is attributable to genetic background, environmental triggers are thought to play a role in the development of autoimmune thyroid disease in susceptible individuals. CONCLUSIONS: Understanding the association of environmental agents with thyroid dysfunction can be utilized to reduce the risk to populations. Knowledge of the specific factors that trigger autoimmune thyroid disease and their mode of action, however, may also inform risk reduction in the individual patient. These factors are especially relevant for those at increased risk of autoimmune thyroid disease based on family history.

Is the current iodine content in edible salt appropriate for eliminating iodine deficiency in China.

OBJECTIVE: This study was designed to measure the urinary iodine excretion of volunteers who daily consumed iodized salt and to evaluate whether the current iodine content in salt is appropriate. A field trial study was then conducted to determine how the salt iodization content should be adjusted, either to prevent iodine deficiency or to avoid excess consumption. METHODS: A total of 1,099 volunteers from 399 households from urban and rural regions were selected. The levels of salt iodine and urinary iodine were measured prior to the field trial. All the households were randomly divided into four groups according to different salt iodine concentrations: group A, 6+/-2 mg/kg; group B, 15+/-2 mg/kg, group C, 24+/-2 mg/kg; and group D, 34+/-2 mg/kg. The urinary iodine levels of households were determined over five consecutive days, starting on the 27th day after the intervention. RESULTS: Before the intervention, the median urinary iodine excretions for urban and rural residents are 294 microg/L and 509 microg/L, respectively. By contrast, urinary iodine excretion in all groups significantly declined after the intervention. The median excretions of urinary iodine on the 28th day after the intervention for all groups were 97.2 microg/L, 199 microg/L, 249 microg/L and 331 microg/L for urban residents, and 101 microg/L, 193 microg/L, 246 microg/L and 308 microg/L for their rural counterparts, respectively. CONCLUSIONS: The trial exhibits a tendency of slightly excessive iodine intake among the households under the currently recommended standard.

Iodine intake and maternal thyroid function during pregnancy.

BACKGROUND: An adequate iodine intake during pregnancy is essential for the synthesis of maternal thyroid hormones and normal brain development in the fetus. Scant evidence is available on the effects and safety of iodine supplementation during pregnancy in areas with adequate or mildly deficient iodine intake. We examined the association of maternal iodine intake and supplementation with thyroid function before 24 weeks of gestation in population-based samples from 3 different areas in Spain. METHODS: A cross-sectional study of 1844 pregnant women (gestational age range 8-23 weeks) was carried out in 3 areas in Spain (Guipúzcoa, Sabadell, Valencia), during the period 2004-2008. We measured levels of free thyroxine and thyroid-stimulating hormone (TSH) in serum, iodine in a spot urine sample, and questionnaire estimates of iodine intake from diet, iodized salt and supplements. Adjusted associations were assessed by multiple linear regression and logistic regression analyses. RESULTS: There was an increased risk of TSH above 3 muU/mL in women who consumed 200 microg or more of iodine supplements daily compared with those who consumed less than 100 microg/day (adjusted odds ratio = 2.5 [95% confidence interval = 1.2 to 5.4]). We observed no association between urinary iodine and TSH levels. Pregnant women from the area with the highest median urinary iodine (168 microg/L) and highest supplement coverage (93%) showed the lowest values of serum free thyroxine. (geometric mean = 10.09 pmol/L [9.98 to 10.19]). CONCLUSIONS: Iodine supplement intake in the first half of pregnancy may lead to maternal thyroid dysfunction in iodine-sufficient or mildly iodine-deficient populations.

Iodine overload and severe hypothyroidism in two neonates.

Iodine overload frequently leads to transient hyperthyrotropinemia or hypothyroidism, and rarely to hyperthyroidism in neonates. Iodine exposure can be prenatal, perinatal or postnatal. Herein we report two newborn infants who developed severe hypothyroidism due to iodine overload. The overloading was caused by excessive use of an iodinated antiseptic for umbilical care in the first case, and as a result of maternal exposure and through breast milk with a high iodine level in the second case. Presenting the two cases, we wanted to draw attention to these preventable causes of hypothyroidism in infants.

Death by oral ingestion of iodine.

We report the clinical and toxicological features of a case of fatal iodine ingestion, and summarize the physiology, clinical characteristics and management of iodine ingestion. Physicians are likely to have little experience in managing such patients, particularly with the advent of less toxic preparations, and therefore need ready access to management guidelines. This case also highlights the potential for substances to retain their toxicity over long periods of time.

[Analytical aspects of the semiquantitative determination of urinary iodine using ferroin: value of rapid screening for iodine deficiency or excess]. / Aspects méthodologiques de la détermination semi-quantitative de l'iodurie par la ferroïne: intérêt dans le dépistage rapide de carence ou surcharge en iode.

Iodine is an essential element for thyroid hormone synthesis. Iodine disorders induced biological and/to clinical expression of thyroid dysfunction. Inappropriate iodine intake (by default or by excess) is worrying in terms of public health in France regarding the iodine deficiency and the frequency of iatrogen iodine overloads. Urinary iodine determination which generally implicates the use of a cerimetric method, is an useful tool to evaluate iodine intakes. In this study, we described the analytical aspects of a semiquantitative method of urinary iodine using a redox indicator, ferroin. This method allows the screening of iodine excess or deficiency in a short time (< 3 hours) with a good specificity and sensitivity. Since this assay does not require specific apparatus, it could be easily developed in clinical chemistry laboratories for the detection of inappropriate iodine intakes, and could be useful for prevention programs of iodine deficiency.

Iodine toxicity and its amelioration.

Iodine (I) toxicity is rare in animals and humans, but nuclear explosions that give off radioactive I and excessive stable I ingestion in parts of the world where seaweed is consumed represent specialized I toxicity concerns. Chronic overconsumption of I reduces organic binding of I by the thyroid gland, which results in hypothyroidism and goiter. Bromine can replace I on position 5 of both T(3) and T(4) with no loss of thyroid hormone activity. Avian work has also demonstrated that oral bromide salts can reverse the malaise and growth depressions caused by high doses of I (as KI) added as supplements to the diet. Newborn infants by virtue of having immature thyroid glands are most susceptible to I toxicity, whether of stable or radioactive origin. For the latter, the 1986 Chernobyl nuclear accident in Belarus has provided evidence that KI blockage therapy for exposed individuals 18 years of age and younger is effective in minimizing the development of thyroid cancer. Whether bromide therapy has a place in I toxicity situations remains to be determined.

Oral iodine toxicity in chicks can be reversed by supplemental bromine.

Four chick bioassays were conducted to quantify iodine (I) toxicity and its amelioration in young chicks. A supplemental I level from KI of 600 mg/kg depressed growth in chicks fed methionine-deficient diets but not in those fed methionine-adequate diets. An I dose level >or= 900 mg/kg was required to cause growth depression in chicks fed a methionine-adequate corn-soybean meal diet. Iodine intoxicated chicks also displayed neurological symptoms and extreme malaise, but dose levels up to 1200 mg I/kg had no effect on blood hemoglobin or hematocrit. Supplemental I levels of 1000-1500 mg/kg caused severe growth depressions that could be totally reversed by dietary addition of 50 or 100 mg/kg bromine provided as NaBr. Nuclear accidents or terrorist actions that result in I toxicity and thyroid cancer or goiter may benefit from use of NaBr as a therapeutic agent.

[An epidemiological study on factors affecting serum thyroglobulin levels].

OBJECTIVE: To investigate the effects of several factors affecting serum thyroglobulin (TG) levels among people aged 14 or more. METHODS: We selected Panshan with median urinary iodine (MUI) 83.45 micro g/L as a deficient iodine intake community, Zhangwu with MUI 242.85 micro g/L as a sufficient iodine intake community and Huanghua with MUI 650.87 micro g/L as an excessive iodine intake community. Serum TG and thyroid stimulating hormone (TSH) were measured in 3,335 subjects whose thyroglobulin antibody (TGAb) were negative and thyroid volume were examined using B-ultrasound. RESULTS: In the population with MUI of 80 - 650 micro g/L, serum TG levels presented a "V" curve. An elevated serum TG was found in both the communities with deficient iodine intake and excessive iodine intake. The same trend was shown in the groups with different levels of serum TSH. An elevated serum TG was found in both the groups of TSH < 0.3 mU/L and TSH > 4.8 mU/L. The serum TG levels was positively correlated with thyroid volume and was higher in female subjects than in male. An increased serum TG was found in subjects of aged 50 in the community with deficient iodine intake. CONCLUSION: Serum TG level is affected by gender, amount of iodine intake, serum TSH level and thyroid volume.

[Iodine intoxication after subcutaneous irrigations of povidone iodine]. / Intoxication à l'iode après irrigations sous-cutanées de povidone iodée.

Irrigation of povidone iodine considered as a safe and effective procedure, is frequently used for deep infections. We report a case of intoxication by iodine in a man of 68-year-old after subcutaneous irrigations of Betadine at a concentration of 20% for a subcutaneous infection of the thigh. Abnormalities of cardiac conduction, lactic acidosis, acute renal failure, hypocalcaemia and thyroid dysfunction were the manifestations of the intoxication confirmed by a very high level of total blood iodine and urine iodine.

Iodine toxicity treated with hemodialysis and continuous venovenous hemodiafiltration.

Continuous mediastinal irrigation with povidone-iodine is used commonly for treating severe postoperative mediastinitis. However, concurrent iodine toxicity has been reported, particularly in patients with renal dysfunction (likely because absorbed iodine is renally excreted). The authors were consulted on a 45-year-old patient with mediastinitis who had renal and hepatic dysfunction while being treated with mediastinal irrigation of povidone-iodine. The povidone-iodine irrigation was discontinued because he had toxic plasma iodine levels. Despite this, his condition worsened, and the iodine levels remained elevated. Thus, hemodialysis (HD) was initiated using high-flux membranes followed by continuous venovenous hemodiafiltration (CVVHDF; 2 L/h of hemofiltration and 2 L/h of HD). Plasma and effluent iodine levels were measured repeatedly to determine iodine clearance by these 2 modalities (HD, 120 mL/min; CVVHDF, 37 mL and 44 mL/min on days 1 and 2, respectively). Hepatic and renal functions improved with decreasing plasma iodine levels. Based on this experience and after reviewing the literature the authors conclude that: (1) iodine irrigation can increase blood iodine levels significantly, especially in the setting of renal failure, and lead to increased morbidity and mortality; (2) plasma iodine levels should be monitored in patients with renal insufficiency; and (3) HD and CVVHDF are effective at clearing iodine. The authors suggest that patients that are at high risk or already developing signs of iodine toxicity should have the iodine irrigation discontinued and may benefit from renal replacement therapy (RRT). Alternatively, concomitant RRT during iodine irrigation may be attempted to maintain the systemic iodine levels at nontoxic levels.

[Meta-analysis on the relationship between children's intelligence and factors as iodine deficiency, supplement iodine and excessive iodine].

OBJECTIVE: To estimate the role and extent of iodine deficiency, iodine supplement and iodine excess on mental development of children. METHODS: Meta-analysis was applied to study 128 independent items from 63 published and non-published papers and reports. The standards of references collected included: age of sample declared by references was 5 - 15; belong to comparison study; children lived in iodine deficiency disorders (IDD) and iodine excess areas; no difference of social economic and culture development level between the study group and the control group. RESULTS: Sixty-seven percent and 79% of the reports mainly involved severe IDD areas respectively. Hunter test of each studies, i.e. iodine deficiency, iodine supplement and excessive iodine group had not discovered statistic difference at the level of alpha = 0.05. The weighted average ES of damage affecting on children's intelligence by iodine deficiency achieved 0.69, which was equivalent to a marked drop in 10.4 IQ points [95% confidence interval (CI): 9.9 - 10.9] when comparing with the children living under non-IDD. The weighted average ES of protective effect on children's intelligence by iodine supplement reached 0.81, which meant that the IQ of children born after correction of iodine deficiency increased 12.2 points (95% CI: 11.5 - 12.9) in comparison with those born at least one year before the correction of iodine deficiency. Most of the references about the relationship between iodine excess and intelligence were gathered from proceedings, while the others were from journals. They location were in some areas of Shandong, Hebei, Shanxi and Inner Mongolia. The mean ES of the role of iodine excess on intelligence was 0.21, which was corresponding to 3.2 IQ points (95% CI: 2.5 - 4.0). CONCLUSION: 1) Iodine deficiency played a role of intermediate strength compared with other causes in delaying brain development making children to be at least 10 IQ points loss in IDD areas. 2) Effective iodine supplement plays a remarkable strengthening role in promoting brain development and can cause 12 IQ points increase for children who were born after the correction of iodine status. 3) Iodine excess has not shown significant important role in children's intelligence.