High iodine effects on the proliferation, apoptosis, and migration of papillary thyroid carcinoma cells as a result of autophagy induced by BRAF kinase.

Papillary thyroid carcinoma (PTC) is a common endocrine tumor. This study found that different iodine concentrations affected the proliferation, apoptosis, and migration of PTC. For this study, we collected clinical information from PTC patients and monitored the levels of urinary iodine, LC3-II, and caspase-3 in cancer tissue, and BRAF kinase in peripheral blood from PTC patients. We also monitored the proliferation, apoptosis and migration ability of human papillary-thyroid carcinoma (BCPAP) cells at different iodine concentrations and their association with changes in autophagy and BRAF kinase activity of BCPAP cells at high iodine levels (10-3 mol/l). We found that the proportion of tumor diameters ≥ 1 cm in the iodine excess group were lower than that in the iodine non-excess group. The proportion of PTC patients with infiltration in the iodine excess group was higher than that in the iodine non-excess group. Levels of the autophagy-related protein LC3-II and the apoptosis-related protein caspase-3 in cancer tissues, and activity of BRAF kinase in peripheral blood, were positively correlated with urinary iodine concentrations from PTC patients. At high iodine levels, the proliferation rate decreased, and apoptosis percentage and migration rates increased compared with the no-iodine group. At high iodine levels, the frequencies of autophagosomes (Aph) and autophagosome-lysosomes (Apl) in BCPAP cells increased significantly, and activities of LC3-II and BRAF kinase increased, respectively. The activity of LC3-II decreased when BRAF kinase was inhibited. The activity of LC3-II and the proliferation and migration rates of BCPAP cells decreased, and the apoptosis percentage increased when autophagy was inhibited at high iodine concentrations. Our results demonstrated that, in the presence of excessive iodine, the mean tumor size of PTC patients was smaller and easier to invade than tumors in patients not supplied with excessive iodine. The levels of autophagy and apoptosis in PTC cancer tissues, and activities of BRAF kinase in peripheral blood increased with increasing urinary iodine concentrations. High iodine levels inhibited cell proliferation and promoted apoptosis and migration of PTC cells. Autophagy induced by BRAF kinase in PTC cells was involved in anti-apoptosis, and promoted proliferation and migration at high iodine concentrations. This study provides a rationale for iodine supplementation in PTC patients.

A critical review of food-associated factors proposed in the etiology of feline hyperthyroidism.

Since the first description of feline hyperthyroidism (HT) in 1979, several studies have been undertaken to define the etiology of the disease. Epidemiologic studies, after investigating non-food- and food-associated factors, suggest a multifactorial etiology. However, in the absence of prospective cohort studies that can confirm a cause-and-effect relationship between HT and associated risk factors, no causative factor for HT has been identified to date. Feline HT resembles toxic nodular goiter in humans, with autonomously functioning upregulated iodide uptake systems. Contribution of the diet to HT development remains controversial. The purpose of this paper is to review critically the reported food-associated risk factors for HT.

Thyroid and iodine nutritional status: a UK perspective.

Iodine is an essential component of the thyroid hormones, which play a crucial role in brain and neurological development. At least one-third of the world's population is estimated to be iodine deficient predominantly in developing countries. Recently concern had also been expressed about the iodine status in industrialised countries such as the UK. A recent survey of the UK iodine status found that that more than two-thirds of schoolgirls aged 14-15 years were iodine deficient due to the reduced milk intake. Maternal iodine deficiency in pregnancy is correlated with cognitive outcomes such as intelligence quotient and reading ability in offspring. No randomised trial data exist for iodine supplementation in mild-moderate iodine-deficient pregnant women. It is possible to combine population interventions to reduce population salt intake with salt iodisation programmes in order to maintain adequate levels of iodine nutrition.

Nutrition and brain development in early life.

Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy.

[Iodine intake during pregnancy: effects on thyroid function in mother and child]. / Ingesta de yodo durante el embarazo: efectos en la función tiroidea materna y neonatal.

INTRODUCTION: Recent studies in Spain have shown an inadequate iodine intake in a significant proportion of pregnant women. Pregnancy increases thyroid hormone requirements, and adequate iodine intake is therefore needed. MATERIAL AND METHODS: One hundred and forty-seven women in their third trimester (week 37) of pregnancy provided a blood sample and a 24-hour urine sample to test serum and urine iodine levels and completed a food frequency questionnaire to assess iodine intake during pregnancy. Serum TSH levels were measured in the babies born to the 140 mothers in the postpartum group. RESULTS: Only 10.9% of pregnant women consumed more than 250 µg iodine daily, and 24.4% of them consumed less than 100 µg daily. Mean free T4 levels were 9.37 pmol/L, and 74 women (54.41%) had levels below the hypothyroxinemia threshold. TSH levels were normal in 135 newborns (96.4%), while 5 (3.6%) had levels higher than 5 µU/mL.

[Iodine and thyroid: what a clinic should know]. / Iodo e tiróide: o que o clínico deve saber.

The World Health Organization considers iodine deficiency as a major worldwide cause of mental and development diseases, estimating that about 13% of the world population is affected by diseases caused by iodine deficiency. Iodine is a trace element necessary for the synthesis of thyroid hormones which, since it cannot be formed by the organism, must be taken regularly with food. Fish and shellfish are generally a good source, because the ocean contains a considerable amount of iodine. On the contrary, plants which grow in iodine-deficient soils are poor in this element, as well as meat and other animal products fed in plants low in iodine. Salt is the best way for iodine supplementation. Cooking the food with iodized salt is a desirable practice because it guarantees the presence of this element. There are also other methods to provide iodine to the general population, such as adding iodine to drinking water or taking supplements of iodine. In pregnancy is recommended iodine supplementation, except in patients with known thyroid disorders. Iodine is an essential component of thyroid hormones (T4 and T3). Inadequate iodine intake leads to inadequate thyroid hormone production. The most important consequences of iodine deficiency, in the general population are goiter and hypothyroidism, and in the severe cases, mental retardation, cretinism and increased neo-natal and infant mortality. The International Council for the Control of Iodine Deficiency Disorders (ICCIDD) formed in 1985, with the only aim of achieving optimal iodine nutrition in the world, in cooperation with UNICEF and WHO. In Portugal, recent studies show significant deficiencies in pregnancy and The Portuguese Society of Endocrinology Diabetes and Metabolism, in partnership with General Directorate of Health, proposed an iodine supplementation during pregnancy with 150-200µg/day.

Role of iodine, selenium and other micronutrients in thyroid function and disorders.

Micronutrients, mostly iodine and selenium, are required for thyroid hormone synthesis and function. Iodine is an essential component of thyroid hormones and its deficiency is considered as the most common cause of preventable brain damage in the world. Nowadays about 800 million people are affected by iodine deficiency disorders that include goiter, hypothyroidism, mental retardation, and a wide spectrum of other growth and developmental abnormalities. Iodine supplementation, under form of iodized salt and iodized vegetable oil, produced dramatic improvements in many areas, even though iodine deficiency is still a problem not only for developing countries. In fact, certain subpopulations like vegetarians may not reach an adequate iodine intake even in countries considered iodine-sufficient. A reduction in dietary iodine content could also be related to increased adherence to dietary recommendations to reduce salt intake for preventing hypertension. Furthermore, iodine intakes are declining in many countries where, after endemic goiter eradication, the lack of monitoring of iodine nutrition can lead to a reappearance of goiter and other iodine deficiency disorders. Three different selenium-dependent iodothyronine deiodinases (types I, II, and III) can both activate and inactivate thyroid hormones, making selenium an essential micronutrient for normal development, growth, and metabolism. Furthermore, selenium is found as selenocysteine in the catalytic center of enzymes protecting the thyroid from free radicals damage. In this way, selenium deficiency can exacerbate the effects of iodine deficiency and the same is true for vitamin A or iron deficiency. Substances introduced with food, such as thiocyanate and isoflavones or certain herbal preparations, can interfere with micronutrients and influence thyroid function. Aim of this paper is to review the role of micronutrients in thyroid function and diseases.

Iodine: deficiency and therapeutic considerations.

Iodine deficiency is generally recognized as the most commonly preventable cause of mental retardation and the most common cause of endocrinopathy (goiter and primary hypothyroidism). Iodine deficiency becomes particularly critical in pregnancy due to the consequences for neurological damage during fetal development as well as during lactation. The safety of therapeutic doses of iodine above the established safe upper limit of 1 mg is evident in the lack of toxicity in the Japanese population that consumes 25 times the median intake of iodine consumption in the United States. Japan's population suffers no demonstrable increased incidence of autoimmune thyroiditis or hypothyroidism. Studies using 3.0- to 6.0-mg doses to effectively treat fibrocystic breast disease may reveal an important role for iodine in maintaining normal breast tissue architecture and function. Iodine may also have important antioxidant functions in breast tissue and other tissues that concentrate iodine via the sodium iodide symporter.

Influence of iodine on the reference interval of TSH and the optimal interval of TSH: results of a follow-up study in areas with different iodine intakes.

OBJECTIVE: The aim of the present study was to evaluate whether the status of iodine nutrition influences the TSH concentration in a selected Chinese reference population according to the criteria proposed by National Academy of Clinical Biochemistry (NACB) and regular thyroid ultrasonography, to establish a new reference interval of TSH based on the wide variation of iodine nutrition in populations, and to identify an optimal interval of TSH by following up the cohort with normal TSH concentrations at baseline. DESIGN: The study was conducted in Panshan, Zhangwu and Huanghua, the regions with mildly deficient, more than adequate and excessive iodine intake, respectively. Of the 3761 unselected subjects who were enrolled at baseline, 2237 met the criteria for a reference population. Of 3048 subjects with normal serum TSH at baseline, 2727 (80.0%) participated in the 5-year follow-up study. TSH and thyroid autoantibodies in serum and iodine in urine were measured, and B-mode ultrasonography of the thyroid was performed. RESULTS: In the reference population, there was a urinary iodine-related increment of serum TSH levels (r = 0.21, P = 0.000), and the mean levels of TSH in Panshan, Zhangwu and Huanghua were 1.15, 1.28 and 1.93 mIU/l, respectively (P = 0.000), corresponding to the rising regional iodine intake. Based on the overall data, we obtained a reference interval of 0.3-4.8 mIU/l. TSH concentrations obtained in the follow-up study correlated well with those at baseline (r = 0.58, P = 0.000). A baseline serum TSH > 1.9 mIU/l was associated with an increased incidence of development of supranormal TSH and a baseline serum TSH < 1.0 mIU/l was associated with an increased incidence of subnormal TSH development. CONCLUSIONS: Iodine nutrition is an important factor associated with TSH concentration even in the rigorously selected reference population. Baseline TSH of 1.0-1.9 mIU/l is an optimal interval with the lowest incidence of abnormal TSH in 5 years.

Iodine in human milk: perspectives for infant health.

Iodine is essential for normal growth, mental development, and survival of infants. The main source of iodine for breastfeeding infants is the iodine found in human milk. Despite the importance of iodine for infant health, there have been limited studies addressing human milk iodine concentrations. The newly recommended Adequate Intake of iodine for infants is 110 microg/day for infants 0-6 months and 130 microg/day for infants 7-12 months. Further studies of human milk iodine are needed to ensure that iodine prophylaxis is providing sufficient iodine for mothers and infants worldwide.

Role of iodine in evolution and carcinogenesis of thyroid, breast and stomach.

The authors have hypothesized that dietary iodine (deficiency or excess) is associated with the development of some gastric and mammary cancers, as it is well-known for thyroid cancer. They report a short review of their own work and of the general literature on this correlation and on the antioxidant function of iodide in stomach, breast and thyroid. Thyroid cells phylogenetically derived from primitive iodide-concentrating gastroenteric cells which, during evolution, migrated and specialized in uptake and storage of iodine, also in order to adapt the organisms from iodine-rich sea to iodine-deficient land. Mammary cells also derived from primitive iodide-concentrating ectoderm. Stomach, breast and thyroid share an important iodide-concentrating ability and an efficient peroxidase activity, which transfers electrons from iodides to the oxygen of hydrogen peroxide and so protects the cells from damage caused by lipid peroxidation. The authors suggest that iodide might have an ancestral antioxidant function in all iodide-concentrating cells from primitive Algae to more recent Vertebrates. In Italy, gastric cancer is more frequent in farmers and in iodine-deficient populations, living in mountainous and hilly areas, than in fishermen. In the last two decades, Italian decrease of gastric cancer seems to be correlated more to the higher dietary consumption of iodine-rich fish rather than to consumption of fruit and vegetables, which indeed has decreased in Italy.

Effects of iodine repletion on thyroid morphology in iodine and/or selenium deficient rat term fetuses, pups and mothers.

It has been suggested that selenium deficiency aggravates the iodine-induced thyroid inflammation and necrosis in iodine-deficient Wistar rats and possibly in man. Studies were carried out to determine whether large amounts of iodine given to iodine-deficient pregnant Sprague-Dawley rats with or without selenium deficiency would induce inflammation and necrosis in their term fetal thyroids. Iodine deficiency was induced in the dams by a low iodine diet or perchlorate in the drinking water and iodine excess was achieved by iodinated drinking water during pregnancy or daily subcutaneous injections of iodine from days 20 to 22 of pregnancy, 1 day after perchlorate was discontinued. Studies were also carried out in 30-day-old pups whose nursing mothers were iodine-deficient (perchlorate) with or without selenium deficiency from conception onward. The administration of iodine restored the morphologic changes in the thyroid induced by iodine deficiency, irrespective of selenium status, toward normal without inflammatory changes or necrosis. Possible explanations for these unexpected findings are discussed.

Body iodine status in school children and availability of iodised salt in Calcutta.

Success of Universal Salt Iodization (USI) programme depends on availability of iodised salt to consumers, which should be reflected in their body iodine status. From a monitoring study in Calcutta, it was found that all packed salts were iodised and most of them (98.1% at household level and 93.6% at retailers' outlets) had iodine at a level of > or = 15 ppm. Of the loose salts, 34.6% at household level and 19.9% at retailers' outlet had iodine level < 15 ppm. A few number (0.5% at household level and 1.0% at retailers' outlets) of salts had no iodine. To ascertain the impact of consumption of iodised salt iodine excreted in urine (UIE) was measured in school children of age between 8-12 years of south, east, west, north and central parts of Calcutta. 22.95% of male children and 31.81% of female children had urinary iodine level less than 50 micrograms/l, which is cut off figure of public health concern. Children from poor slum areas were found to be at greater risk.

PIP: This paper presents a monitoring study on the availability of iodized salt at retailers' outlets and at the household level in Calcutta, as well as the impact of its consumption among school children aged 8-12 years. The children were physically examined for 3 grades of goiter. Urine samples were collected to estimate iodine excretion. Various types of salts were gathered from retailers' outlets located within a 0.5 km radius of the school that the children attended. Spot test kit and iodimetric titration methods were used in monitoring the availability of iodized salt. Results showed that all packed salts were iodized and that a majority of them (98.1% at the household level and 93.6% at the retailers' outlet level) had iodine levels of 15 ppm or higher. Only a small percentage of salts (0.5% at the household level and 1.0% at the retailers' outlet level) had no iodine content. As to the urinary iodine content among school children, 22.95% of males and 31.81% of females had urinary iodine level less than 50 mcg/l. 77% of male children and 69% of female children had satisfactory urinary iodine levels (50 mcg/l). The results confirmed the success of the Universal Salt Iodization (USI) program with regard to the availability of iodized salt.

Thyroid function.

Normal thyroid status is dependent on the presence of many trace elements for both the synthesis and metabolism of thyroid hormones. Iodine is most important as a component of the hormones, thyroxine and 3,3',5-tri-iodothyronine (T3) and iodine deficiency may affect approximately one billion people throughout the world. Selenium is essential for normal thyroid hormone metabolism being involved with selenium-containing iodothyronine de-iodinases that control the synthesis and degradation of the biologically active thyroid hormone, T3. Additionally, selenoperoxidases and thioredoxin reductase protect the thyroid gland from peroxides produced during the synthesis of hormones. The roles of iron, zinc and copper in the thyroid are less well defined but sub- or supraoptimal dietary intakes of all these elements can adversely affect thyroid hormone metabolism.

[Iodine and thyroid function]. / Iode et fonction thyroïdienne.

Iodine is a raw material for the thyroid production of hormone which is on the major external control of TSH. The thyroid adaptation to iodine deficiency consists in an increasing iodine concentration from the circulation, an enhancing iodination of the tyrosyl residues in thyroglobulin, a decreasing iodine storage associated to a better recycling of non hormonal iodine and thyroid hyperplasia to provide more synthetic possibilities. Genetic variation and environmental factors explain the wide variation of individuals response to iodine deficiency resulting in a high prevalence of goiter, a mild TSH level increase or overt hypothyroidism. At long term iodine deficiency may have severe pathological consequences and induce neuropsychological deficits in school-children. A policy of iodine supplementation mainly by iodized salt must be undertaken in many areas in the world. Effects of an iodine excess on thyroid function are variable depending upon the underlying thyroid disorder and ambient iodine intake. The most subjects remain euthyroid by mechanisms of autoregulation based on an inhibition of thyroid hormone synthesis and a decrease in the thyroid iodide trap. Euthyroid individuals from high iodine intake areas or those with a history of lymphocytic thyroiditis, treated Graves' disease or subtotal thyroidectomy develop hypothyroidism. On the other hand iodine induced hyperthyroidism is more common in areas of iodine deficiency and in older patients with nodular goiter.

Trace elements in nutrition for premature infants.

Ten trace elements that are nutritionally essential include: zinc, copper, selenium, chromium, manganese, molybdenum, cobalt, fluoride, iodine, and iron. This article briefly reviews the biochemistry of these trace elements, describes clinical deficiency states, and provides a rationale for recommended enteral and parenteral intakes for preterm infants.