Iodine-induced Hypothyroidism Research Articles

Iodine-Induced Hypothyroidism and Long-Term Risks of Incident Heart Failure.

Background Although most individuals can adapt to a large iodine load and remain euthyroid, hypothyroidism can develop after iodine exposure. Hypothyroidism is associated with adverse cardiovascular consequences, including heart failure. This study was performed to investigate the relationships between iodine-induced hypothyroidism and incident heart failure. Methods and Results This cohort study of the US Veterans Health Administration (1998-2021) included adults aged ≥18 years with a serum thyroid-stimulating hormone (thyrotropin) <60 days of iodine contrast administration, and <1 year of a baseline normal serum thyroid-stimulating hormone. Cox proportional hazards regression ascertained risk of incident heart failure following iodine-induced hypothyroidism, adjusting for age, sex, race and ethnicity, body mass index, and history of coronary heart disease, dyslipidemia, diabetes, and hypertension. Of 45 470 veterans (mean±SD age, 61.1±14.1 years; 88% men), 3361 (7.4%) developed iodine-induced hypothyroidism. Heart failure developed in 5685 (12.5%) individuals over a median follow-up of 3.6 years (interquartile range, 1.9-7.2 years). Adjusted for risk factors, iodine-induced hypothyroidism was associated with increased risk of heart failure, compared with those who remained euthyroid after iodine exposure (adjusted hazard ratio [HR], 1.11 [95% CI, 1.01-1.22]). Women were at greater risk than men (adjusted HR: women, 1.65 [95% CI, 1.13-2.40]; men, 1.08 [95% CI, 0.98-1.19]; P for interaction, 0.02). Conclusions In the largest US study of this topic, hypothyroidism following iodine exposure was associated with an increased risk of incident heart failure, particularly in women. These findings support the need for further research to address the clinical significance of this issue, including the possible sex-specific risks of incident heart failure in more diverse data sets and study populations.

Iodine-induced hypothyroidism (IIH) in paediatric patients receiving peritoneal dialysis: Is risk mitigation possible?

Children with kidney failure who receive maintenance peritoneal dialysis (PD) are at increased risk for thyroid dysfunction. A poorly appreciated cause of hypothyroidism related to PD is iodine overload from exposure to iodine-containing cleaning solutions, iodinated contrast agents or povidone-iodine-containing PD caps, particularly in infants and small children. An international survey was conducted to understand current practices regarding iodine exposure in PD patients, the frequency of iodine-induced hypothyroidism (IIH) in patients receiving PD, and to assess awareness of this issue among paediatric nephrologists. Eighty-nine paediatric nephrology centres responded to the survey. Hypothyroidism in PD patients was diagnosed in 64% (n = 57) of responding centres, although only 19 of these centres (33%) suspected or diagnosed IIH. Aetiologies of IIH included exposure to povidone-iodine-containing PD caps (53%), cleaning solutions with iodine (37%) and iodinated contrast (10%). While most centres (58%, n = 52) routinely evaluate thyroid function, only 34% (n = 30) specifically aim to limit iodine exposure. Of centres not routinely evaluating for or utilising methods to prevent iodine exposure and hypothyroidism, 81% reported being unaware of the risk of IIH in PD patients. Hypothyroidism is diagnosed in a substantial percentage of paediatric PD programmes internationally. Increased education on the risk of iodine exposure in children receiving PD may decrease the incidence of IIH as an aetiology of hypothyroidism.

Radioactive Iodine-induced hypothyroidism interferes with the maturation of reproductive organs during puberty in immature female rats.

Animal and human studies suggest that thyroid hormone may have critical roles in the development of the ovary. For example, thyroid deficiency disrupts the ovarian microarchitecture and menstrual cycle in neonate and adult women, respectively. Therefore, it is conceivable that thyroid deficiency might disrupt sexual maturation during the peri-pubertal period. To investigate the impact of radioactive iodine-induced thyroid deficiency on reproductive organs throughout puberty, immature female rats were given water containing radioactive iodine (0.37MBq/g body weight) twice, on postnatal days 22 and 29. Radioactive iodine-induced hypothyroidism was revealed by low free thyroxin levels. Thyroid deficiency delayed the onset of vaginal opening, reduced ovarian weight and the number of medium-sized follicles and led to elongated uteri. However, there was no effect on the estrous cycle or absolute uterus weight. We conclude that radioactive iodine-induced thyroid deficiency delays sexual maturation and alters normal ovarian growth in peri-pubertal rats.

Iodoral-Induced Iatrogenic Hypothyroidism

Background: Iodine is essential for the formation of thyroid hormones. Therefore, the thyroid gland is generally able to maintain normal hormone synthesis despite changes in iodine availability. When there is an increase in iodide load, the thyroid gland is able to inhibit the formation of organic iodide via the Wolff-Chaikoff effect (WCE). This prevents the formation of large quantities of thyroid hormones, thus preventing hyperthyroidism1. Continued exposure to excess iodine is also overcome by the “escape” phenomenon and hormone synthesis resumes in a normal fashion2. However, some patients may lack this autoregulation and develop hypothyroidism. Clinical Case: An 86-year-old male with a history of subclinical hypothyroidism initially presented to his PCP for evaluation of cognitive decline. Workup revealed a TSH of 10 mcIU/mL (0.34 – 5.6 mcIU/mL), a normal FT4 and a negative TPOAb. It was subsequently revealed that the patient was started on Iodoral 12.5 mg daily, an iodine/potassium iodide supplement, 1 month prior to presentation by a naturopathic doctor. Prior to all this, his TSH had always ranged between 4 – 6 mcIU/mL for many years. It was recommended that he discontinue Iodoral and repeat thyroid labs in the future. Despite this, the patient continued on varying doses of Iodoral supplementation. Repeat labs obtained 8 months later revealed an elevated TSH of 99 mcIU/mL and a low FT4 of 0.43 ng/mL (0.6 – 2.6 ng/mL). Despite these numbers, he was asymptomatic and did not exhibit any overt signs of hypothyroidism. He was referred to Endocrinology and finally stopped taking Iodoral.7 weeks post-discontinuation, his repeat labs showed a resolution of hypothyroidism and return to his baseline subclinical disease with a TSH of 8.2 mcIU/mL and a normal FT4. A urine iodine/creatinine was normal at 244.2 ug/g (35 – 540 ug/g) indicating that there was no residual iodine excess from the Iodoral. Conclusion: As far as we are aware, we present the first reported case of Iodoral-induced iatrogenic hypothyroidism. As with past cases of iodine-induced hypothyroidism, our patient had underlying thyroid disease in subclinical hypothyroidism which could explain why he was unable to escape from the WCE. The half-life of Iodoral is unknown but it is generally understood that the effects of iodide are reversed between 2 to 4 weeks after withdrawal. Our patient did not repeat his thyroid function tests until 7 weeks post-discontinuation but did demonstrate a return to baseline with no other intervention. Reference: 1. Markou K, Georgopoulos N, Kyriazopoulou V, Vagenakis AG. Iodine-Induced hypothyroidism. Thyroid. 2001 May;11(5):501-10. doi: 10.1089/105072501300176462. PMID: 11396709.2. Torti JF, Correa R. Potassium Iodide. 2020 Oct 12. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. PMID: 31194460.

Iodine-induced thyroid dysfunction

Iodine-induced thyroid dysfunctions are, despite their rare occurrence, important clinical syndromes. Their immediate recognition can avoid serious consequences. Important triggers can be iodine-containing contrast agents, amiodarone or iodine-containing disinfectants. Iodine-induced hypothyroidism and hyperthyroidism need to be distinguished, whereby the former is usually self-limiting. The aim of this article is to present current knowledge on the pathogenesis, therapy, and prophylaxis of iodine-induced thyroid dysfunction. We performed aliterature search of current publications and linked them to daily clinical experience. In iodine-induced hyperthyroidism, antithyroid drugs and perchlorate are primarily used to decrease thyroid hormone synthesis and further iodine uptake into the thyroid. For the prophylaxis of x‑ray contrast agent-induced hyperthyroidism, perchlorate can be administered in high-risk settings in combination with antithyroid drugs, if possible starting one day before the iodine exposure.

MON-082 The Neonatal Screen That Cried Wolff

Introduction:Hypothyroidism is one of the major causes of preventable mental retardation. Neonatal screening aids in the prompt diagnosis of newborns with congenital hypothyroidism. There are other clinical conditions that can alter thyroid function during the newborn period, including exposure of high iodine concentrations.Case Presentation:One day old female born at 37 3/7 weeks of gestational age by C-section with imperforated anus and congenital heart disease was transferred to our children’s hospital within the first day of life for a hybrid cardiac procedure of bilateral pulmonary artery banding and PDA stenting. She had an Illinois Neonatal screen done at 36 hours of life that was normal. Her cardiac surgery was performed at 10 days of life, where she was exposed to iodine products transdermally. At 14 days of age, she had a repeat Illinois Neonatal screen that was positive for congenital hypothyroidism with a TSH of 78 mIu/mL (normal < 20 mIu/mL) and reflex total T4 of 5.4ug/dL (normal is > 8ug/dL). No family history of thyroid disease; mother was healthy during pregnancy and was not on medications that could affect baby’s thyroid function. Subsequent serum laboratory testing confirmed a TSH of 74.3mIu/mL and Free T4 of 0.6ng/dL. Patient was diagnosed with Wolff-Chaikoff effect, which is the phenomenon of transient hypothyroidism caused by exposure to high doses of iodine (iodine containing contrast agents or topical antiseptics). Pediatric Endocrinology was consulted at 2 weeks of life and she was started on 25mcg of levothyroxine PO daily. Levothyroxine dose decreased at 16 month of age to 12.5mcg due to stable thyroid function tests. The patient was last seen at 30 months of age by Pediatric Endocrinology. She is still on the low dose of levothyroxine and her thyroid labs have been within normal limits for an infant. She will likely not require lifelong thyroid supplementation. Conclusion: Risk of hypothyroidism among neonates must be considered seriously after large iodine exposure and monitoring for transient hypothyroidism should be performed. It is thus recommended that attempts should be made to reduce the amount of iodine used during procedures and to carefully monitor thyroid function in all neonates exposed to an excess of iodine.Reference:Markou, K., et al. “Iodine-Induced Hypothyroidism.” Thyroid, vol. 11, no. 5, 2001, pp. 501–510., doi:10.1089/105072501300176462.Linder N, Sela B, German B, et al. Iodine and hypothyroidism in neonates with congenital heart disease. Archives of Disease in Childhood - Fetal and Neonatal Edition 1997;77:F239-F240.Kovacikova, Lubica, et al. “Thyroid Function and Ioduria in Infants after Cardiac Surgery: Comparison of Patients with Primary and Delayed Sternal Closure.” Pediatric Critical Care Medicine, vol. 6, no. 2, 1 Mar. 2005, pp. 154–159., doi:10.1097/01.pcc.0000154960.59452.06.

Iodinated contrast medium in patients with thyroid disorders

Adequate intake of iodine is essential for normal thyroid function. However, sudden exposure to high amounts of iodine may cause thyroid dysfunction. The aims of this paper are to summarize the literature on the effects of iodinated contrast medium (CM) on thyroid function, the risk to develop CM-induced hyper- and hypothyroidism, and to describe procedures for clinical practice regarding diagnosis, prevention, and treatment of CM-induced hyperthyroidism. The occurrence of CM-induced hyperthyroidism is very rare (<0.5%). In Germany, thyroid function is commonly assessed with laboratory tests (TSH determination) before the use of iodinated CM. Older patients (>60years) with autonomous thyroid and concomitant cardiac diseases are at particular risk of developing hyperthyroidism. The main focus of prevention is to identify patients at risk of developing iodine-induced hyperthyroidism and carry out further thyroid diagnostic procedures prior to CM use. In these patients, prophylaxis with perchlorate and/or thionamides is recommended or alternatively careful monitoring of the patients after use of CM. In patients with overt hyperthyroidism, the use of CM is contraindicated. Iodine-induced hypothyroidism is predominantly found in regions with sufficient iodine supply and in patients with autoimmune thyroiditis. Free iodide influences iodide uptake into the thyroid and therefore interferes with nuclear diagnostic procedures like thyroid scintigraphy as well as radioactive iodine treatment which may be hampered for 2months or longer after use of CM.

Effect of radioactive iodine-induced hypothyroidism on longitudinal bone growth during puberty in immature female rats.

Thyroid cancer in children, the most common endocrine malignancy, shows aggressive behavior and has a high recurrence rate after surgical ablation. Radioactive iodine (RAI) treatment is the most effective primary modality for medical ablation of juvenile thyroid cancer, and leads to intentional hypothyroidism. Although several negative impacts of hypothyroidism have been reported in children in response to other antithyroid agents, the combined effects of RAI exposure and hypothyroidism, on growing bones specifically, are unknown. In this study, we investigated the effect of RAI-induced hypothyroidism on the long bones during the pubertal growth spurt using immature female rats. Female Sprague-Dawley rats were randomly divided into a control group, and an RAI-treated group fed with RAI (0.37 MBq/g body weight) twice via gavage. After 4 weeks, we observed a significantly-reduced serum free thyroxine level in the RAI group. The latter group also displayed decreased body weight gain compared to the control. In addition, the lengths of long bones, such as the leg bones and vertebral column, as well as bone mineral content, were reduced in the RAI-treated animals. Our results confirm the negative impacts of RAI-induced thyroid deficiency during puberty on longitudinal bone growth and bone mineralization.

Effects of Adequate Iodine Supply on the Incidence of Iodine-Induced Thyroid Disorders in Slovenia.

This study aimed to establish the changes in the incidence and characteristics of iodine-induced hyperthyroidism (II-Hyper) and iodine-induced hypothyroidism (II-Hypo) in the two-year period before and the 10-year period after the increase in mandatory salt iodization from the previous 10 mg/kg of potassium iodide to 25 mg/kg in 1999. Furthermore, the aim was to determine the duration of treatment in II-Hyper patients, since no data regarding severity and treatment of II-Hyper with respect to iodine supply are available. This retrospective study reviewed medical records of 885 Slovenian patients first diagnosed with II-Hyper or II-Hypo between 1998 and 2009 at the Thyroid Department of the University Medical Centre Ljubljana. II-Hyper and II-Hypo were diagnosed by one out of 10 senior internal medicine specialists. The diagnosis was based on an adequate patient history, and laboratory measurements of thyrotropin, thyroid hormones, and thyroid antibodies. In most cases, thyroid ultrasound and thyroid scintigraphy were performed. Demographic characteristics and the type and the duration of treatment were also reviewed. The incidence of II-Hypo was significantly higher after the increase in iodine supply than it was before (p < 0.001). After the increase in iodine supply, the incidence of II-Hyper was significantly lower than before the increase (p < 0.001). Furthermore, the portion of patients with overt hyperthyroidism decreased, predominantly due to the increased proportion of patients with subclinical hyperthyroidism (p = 0.007 and p = 0.015, respectively). The duration of treatment with antithyroid drugs and perchlorate was significantly shorter after the increase in iodine supply than it was before (p = 0.001 and p = 0.002, respectively). A significantly positive correlation between the year of the occurrence of excessive iodine intake (EII)-induced thyroid disease and the duration of treatment with amiodarone was found (R = 0.132; p = 0.048), suggesting that the longer the patients had an adequate iodine supply, the longer they could take amiodarone before EII-induced thyroid disorder developed. After the increase in iodine supply, a higher incidence of II-Hypo and a lower incidence of II-Hyper were observed than before the increase. Less severe II-Hyper, shorter duration of treatment of II-Hyper, as well as a longer thyroid disease-free period in patients on amiodarone are additional beneficial clinical consequences after the establishment of an adequate iodine supply.

Iodine Concentration in Breastmilk and Urine among Lactating Women of Bhaktapur, Nepal.

Adequate iodine concentration in breastmilk (BMIC) is essential for optimal neonatal thyroid hormone synthesis and neurological development in breastfed infants. For many decades, iodine deficiency has been a public health problem in Nepal. However, recently, excessive iodine intakes among Nepali infants have been reported. This study aimed to measure BMIC and urinary iodine concentration (UIC) among lactating women in a peri-urban area of Nepal. Iodine concentration was measured in spot urine (n = 485) and breastmilk samples (n = 291) of 500 randomly selected lactating women. The median (p25, p75) BMIC and median UIC were 250 (130, 370) µg/L and 230 (135–377) µg/L, respectively. Around 82% had BMIC > 100 µg/L, 61% had BMIC > 200 µg/L and 81% had UIC > 100 µg/L, 37% had >300 µg/L and 20% had >500 µg/L. In multiple linear regression models, time since birth (β 3.0, 95% CI (0.2, 5.0)) and UIC (β 1.0, 95% CI (0.1, 2.0)) were associated with BMIC, explaining 26% of the variance. A large proportion of the women had adequate BMIC and UIC; however, a subset had high iodine concentrations. These findings emphasize the importance of carefully monitoring iodine intake to minimize the risk of iodine excess and subsequently preventing transient iodine-induced hypothyroidism in breastfed infants.

Effects of potassium iodide in concentrations of TSH, tT3 and tT4 in serum of subjects with sporotrichosis

The saturated potassium iodide solution (SSKI) as treatment for sporotrichosis may cause hypothyroidism by suppressing the synthesis of thyroid hormones (tT3 and tT4 ) and the iodine excess could lead to thyrotoxicosis. Evaluating the changes in serum levels of TSH, tT3 and tT4 in euthyroid patients with sporotrichosis treated with SSKI. For the selection of euthyroid patients, TSH, tT3 and tT4 concentrations were measured for those adults and children diagnosed with sporotrichosis. Each paediatric patient was administered SSKI orally in increasing doses of 2-20 drops/3 times/day and 4-40 drops/3 times/day in adults. Serum concentrations of TSH, tT3 and tT4 were measured 20 days after started the treatment and 15 days posttreatment. Eight euthyroid patients aged between 2 to 65 years old were included. After 20 days of treatment, two suffered subclinical hypothyroidism, one developed subclinical hyperthyroidism, and one hyperthyroxinaemia euthyroid. At 15 days posttreatment only four patients were evaluated and all serum levels of TSH, tT3 and tT4 were normal. Some euthyroid patients with sporotrichosis can develop hyperthyroidism or subclinical iodine-induced hypothyroidism, during the administration of 3 or 6 g SSKI/day.

Iodine-induced thyroid dysfunction

To summarize the mechanisms of iodine-induced hypothyroidism and hyperthyroidism, identify the risk factors for thyroid dysfunction following an iodine load, and summarize the major sources of excess iodine exposure. Excess iodine is generally well tolerated, but individuals with underlying thyroid disease or other risk factors may be susceptible to iodine-induced thyroid dysfunction following acute or chronic exposure. Sources of increased iodine exposure include the global public health efforts of iodine supplementation, the escalating use of iodinated contrast radiologic studies, amiodarone administration in vulnerable patients, excess seaweed consumption, and various miscellaneous sources. Iodine-induced thyroid dysfunction may be subclinical or overt. Recognition of the association between iodine excess and iodine-induced hypothyroidism or hyperthyroidism is important in the differential diagnosis of patients who present without a known cause of thyroid dysfunction.

High Iodine Content of Korean Seaweed Soup: A Health Risk for Lactating Women and Their Infants?

Iodine requirements increase during pregnancy and lactation due to increased maternal thyroid hormone production and iodine excretion, fetal iodine requirements, and loss of iodine in breast milk. Seaweed preparations are a source of dietary iodine. Korean and many Korean-American women traditionally consume brown seaweed soup (Undaria pinnatifida) daily during the early postpartum period (Supplementary Data; Supplementary Data are available online at www .liebertonline.com/thy) (1). This tradition is maintained among Korean and Korean-American women such that their breast milk iodine correlates strongly with frequency and quantity of seaweed soup consumption (2,3). As the iodine content of this soup has not been reported, we randomly selected 10 brands of dried brown seaweed from Korea and China available in the United States. Seaweed soup from each brand was prepared utilizing the following ingredients: 1 oz of dried seaweed, 6 cups water, 1⁄4 pound beef, 11⁄2 tablespoons soy sauce, 2 teaspoons sesame oil, 1 teaspoon garlic, and *1⁄2 teaspoon noniodized sea salt (Supplementary Data). Iodine content of the dried seaweeds and the soups were measured spectrophotometrically after digestion with hydrochloric acid and dilution with iodine free deionized water, as described by Benotti et al. (see Supplementary Data). The mean iodine content of the dried seaweed was 359 254 mg/g (mean SD), or 10173 7200mg/oz. The mean iodine content of seaweed broth was 1.9 0.7 mg/mL, with 1 bowl (250 mL) of broth containing an average of 487 178 mg of iodine. The mean iodine content of blended seaweed soup contents (broth, cooked seaweed) was 1705 930 mg/250 mL. Potential sources of variability in soup iodine (see Supplementary Data) include the iodine contents of dry seaweed and other ingredients (e.g., iodized salt, iodine-containing soy sauce, and anchovy soup base), cooking methodologies, and the quantity of seaweed in recipes (4). The iodine content of seaweed varies with harvest location and season, salinity and temperature of water, depth and portion of seaweed harvested, and storage conditions (4). The World Health Organization (WHO) guidelines recommend 250 mg/day of iodine intake during pregnancy and lactation, whereas the Institute of Medicine (IOM) recommends 220mg/day of iodine intake during pregnancy and 290 mg/day during lactation (Supplementary Data). The IOM recommends a tolerable upper limit of iodine intake of 1100mg/day, whereas the WHO suggests an upper limit of 500mg/day for pregnant and lactating women and 180mg/ day for infants. More than 90% of postpartum lactating Korean women consume seaweed soup at least three times daily in the first postpartum week, and up to 75% of these women have seaweed soup at least once daily up to 4 weeks postpartum (3). Our findings indicate that this constitutes an average iodine intake of at least 1400 mg/day in the first postpartum week based solely on 250 mL seaweed soup broth three times daily, and at least 5000mg/day if the entire contents of each serving are consumed (broth and seaweed). High levels of breast milk iodine values in Korean postpartum women have been reported (2,3). Depending on quantity and frequency of intake, postpartum women who consume Korean seaweed soup may have daily iodine intakes and breast milk iodine concentrations that far exceed the WHO and IOM upper limits. Iodine-induced hypothyroidism, iodine-induced thyrotoxicosis, and iodine-induced goiter are potential adverse effects of excess iodine consumption. However, the effects of high iodine intake are dependent on several factors, including iodine status (i.e., degree and duration of iodine deficiency or sufficiency) before excess iodine exposure, as well as any preexisting thyroid autoimmunity, thyroid dysfunction, and/or thyroid nodularity. Chung et al. reported subclinical hypothyroidism in preterm Korean infants exposed to high iodine content in breast milk (2). Additionally, cases of iodine-induced neonatal hypothyroidism due to maternal seaweed consumption were reported in Australia. Increased incidence and/or exacerbation of postpartum thyroiditis are also potential risks of high iodine intake. However, these effects were not observed in the only Korean study to date evaluating this relationship. Further studies should be carried out to evaluate the potential adverse effects of sustained high dietary iodine in postpartum women of Korean descent and their infants. In addition, there should be a raised cultural awareness among endocrinologists and other medical providers regarding this common source of high dietary iodine. A careful dietary history should be part of the evaluation and follow-up of postpartum Korean women and their infants, especially in the setting of signs and/or symptoms of thyroid dysfunction, thyroid autoimmunity, nodular thyroid anatomy, or pre-existing thyroid dysfunction. In addition, Korean women

Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995-2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9-162.9). When stratified by sex and age-group (00-39, 40-64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

Thyroid and the environment: exposure to excessive nutritional iodine increases the prevalence of thyroid disorders in São Paulo, Brazil

To evaluate the prevalence of chronic autoimmune thyroiditis (CAT) and iodine-induced hypothyroidism, hyperthyroidism (overt and subclinical), and goiter in a population exposed to excessive iodine intake for 5 years (table salt iodine concentrations: 40-100 mg/kg salt). Design This was a population-based, cross-sectional study with 1085 participants randomly selected from a metropolitan area in São Paulo, Brazil, and conducted during the first semester of 2004. Thyroid ultrasound examination was performed in all participants and samples of urine and blood were collected from each subject. Serum levels of thyroid-stimulating hormone, free thyroxine, and anti-thyroid peroxidase (TPO) antibodies, urinary iodine concentration, thyroid volume, and thyroid echogenicity were evaluated. We also analyzed table salt iodine concentrations. At the time the study was conducted, table salt iodine concentrations were within the new official limits (20-60 mg/kg salt). Nevertheless, in 45.6% of the participants, urinary iodine excretion was excessive (above 300 microg/l) and, in 14.1%, it was higher than 400 microg/l. The prevalence of CAT (including atrophic thyroiditis) was 16.9% (183/1085), women were more affected than men (21.5 vs 9.1% respectively, P=0.02). Hypothyroidism was detected in 8.0% (87/1085) of the population with CAT. Hyperthyroidism was diagnosed in 3.3% of the individuals (36/1085) and goiter was identified in 3.1% (34/1085). Five years of excessive iodine intake by the Brazilian population may have increased the prevalence of CAT and hypothyroidism in subjects genetically predisposed to thyroid autoimmune diseases. Appropriate screening for early detection of thyroid dysfunction may be considered during excessive nutritional iodine intake.

Arsenic in Herbal Kelp Supplements: Schenker et al. Respond

Arsenic in Herbal Kelp Supplements: Schenker et al. Respond

Induction of Goitrous Hypothyroidism by Dietary Iodide in SJL Mice

Prolonged intake of large amounts of iodide has been reported to increase the incidence of goiter and/or hypothyroidism in humans as well as animals prone to spontaneous autoimmune thyroiditis. In the current study, we investigated the role of dietary iodide on the development of hypothyroidism, as well as thyroiditis, in strains of mice that do not develop spontaneous autoimmune thyroiditis. Intake of 0.05% NaI via drinking water for 10 wk induced hypothyroidism in SJL/J mice as indicated by elevated TSH and depressed total T(4) values in serum and formation of colloidal goiter with an inactive flattened thyroid epithelium. Hypothyroidism did not appear to have an autoimmune basis because only focal mononuclear cell infiltrates were found intrathyroidally, and antithyroglobulin antibodies or increased organification of iodide were not detected. These phenomena were not observed in similarly treated CBA/J mice, suggesting polymorphisms in genes controlling events downstream of iodide uptake by thyrocytes. Interestingly, RT-PCR analysis indicated that unlike CBA/J, SJL/J mice could not down-regulate Na/I symporter gene expression during the NaI treatment. No significant temporal or strain differences were observed regarding the expression of thyroglobulin, pendrin, thyroid peroxidase, and DUOX1 and DUOX2 genes after NaI intake. Our results point to the generation of a mouse model for the study of iodine-induced hypothyroidism, which does not seem to have an autoimmune basis.

Povidone Iodine-induced Overt Hypothyroidism in a Patient with Prolonged Habitual Gargling: Urinary Excretion of Iodine after Gargling in Normal Subjects

Iodine-induced hypothyroidism that develops in patients who gargle routinely with povidone iodine is well known. Usually the hypothyroidism is mild and resolves spontaneously upon cessation of gargling. Here, we report a 63-year-old patient with overt hypothyroidism that developed due to habitual gargling with povidone iodine for more than 10 years. The urinary excretion of iodine was estimated to be greater than 5 mg/day, based on values obtained from 18 normal subjects who gargled three times a day (4.6+/-2.1 mg, mean+/-SD). After discontinuation of the gargling, the patient has been euthyroid for more than 10 months.

Iodine-Induced hypothyroidism.

Iodine is an essential element for thyroid hormone synthesis. The thyroid gland has the capacity and holds the machinery to handle the iodine efficiently when the availability of iodine becomes scarce, as well as when iodine is available in excessive quantities. The latter situation is handled by the thyroid by acutely inhibiting the organification of iodine, the so-called acute Wolff-Chaikoff effect, by a mechanism not well understood 52 years after the original description. It is proposed that iodopeptide(s) are formed that temporarily inhibit thyroid peroxidase (TPO) mRNA and protein synthesis and, therefore, thyroglobulin iodinations. The Wolff-Chaikoff effect is an effective means of rejecting the large quantities of iodide and therefore preventing the thyroid from synthesizing large quantities of thyroid hormones. The acute Wolff-Chaikoff effect lasts for few a days and then, through the so-called "escape" phenomenon, the organification of intrathyroidal iodide resumes and the normal synthesis of thyroxine (T4) and triiodothyronine (T3) returns. This is achieved by decreasing the intrathyroidal inorganic iodine concentration by down regulation of the sodium iodine symporter (NIS) and therefore permits the TPO-H202 system to resume normal activity. However, in a few apparently normal individuals, in newborns and fetuses, in some patients with chronic systemic diseases, euthyroid patients with autoimmune thyroiditis, and Graves' disease patients previously treated with radioimmunoassay (RAI), surgery or antithyroid drugs, the escape from the inhibitory effect of large doses of iodides is not achieved and clinical or subclinical hypothyroidism ensues. Iodide-induced hypothyroidism has also been observed in patients with a history of postpartum thyroiditis, in euthyroid patients after a previous episode of subacute thyroiditis, and in patients treated with recombinant interferon-alpha who developed transient thyroid dysfunction during interferon-a treatment. The hypothyroidism is transient and thyroid function returns to normal in 2 to 3 weeks after iodide withdrawal, but transient T4 replacement therapy may be required in some patients. The patients who develop transient iodine-induced hypothyroidism must be followed long term thereafter because many will develop permanent primary hypothyroidism.

Escape from the acute Wolff-Chaikoff effect is associated with a decrease in thyroid sodium/iodide symporter messenger ribonucleic acid and protein.

In 1948, Wolff and Chaikoff reported that organic binding of iodide in the thyroid was decreased when plasma iodide levels were elevated (acute Wolff-Chaikoff effect), and that adaptation or escape from the acute effect occurred in approximately 2 days, in the presence of continued high plasma iodide concentrations. We later demonstrated that the escape is attributable to a decrease in iodide transport into the thyroid, lowering the intrathyroidal iodine content below a critical inhibitory threshold and allowing organification of iodide to resume. We have now measured the rat thyroid sodium/iodide symporter (NIS) messenger RNA (mRNA) and protein levels, in response to both chronic and acute iodide excess, in an attempt to determine the mechanism responsible for the decreased iodide transport. Rats were given 0.05% NaI in their drinking water for 1 and 6 days in the chronic experiments, and a single 2000-microg dose of NaI i.p. in the acute experiments. Serum was collected for iodine and hormone measurements, and thyroids were frozen for subsequent measurement of NIS, TSH receptor, thyroid peroxidase (TPO), thyroglobulin, and cyclophilin mRNAs (by Northern blotting) as well as NIS protein (by Western blotting). Serum T4 and T3 concentrations were significantly decreased at 1 day in the chronic experiments and returned to normal at 6 days, and were unchanged in the acute experiments. Serum TSH levels were unchanged in both paradigms. Both NIS mRNA and protein were decreased at 1 and 6 days after chronic iodide ingestion. NIS mRNA was decreased at 6 and 24 h after acute iodide administration, whereas NIS protein was decreased only at 24 h. TPO mRNA was decreased at 6 days of chronic iodide ingestion and 24 h after acute iodide administration. There were no iodide-induced changes in TSH receptor and thyroglobulin mRNAs. These data suggest that iodide administration decreases both NIS mRNA and protein expression, by a mechanism that is likely to be, at least in part, transcriptional. Our findings support the hypothesis that the escape from the acute Wolff-Chaikoff effect is caused by a decrease in NIS, with a resultant decreased iodide transport into the thyroid. The observed decrease in TPO mRNA may contribute to the iodine-induced hypothyroidism that is common in patients with Hashimoto's thyroiditis.