Bioelement effects on thyroid gland in children living in iodine-adequate territory

Endemic goitre is a primary pathology of thyroid gland and critical medico social problem in many countries. A dominant cause of endemic goitre is iodine deficiency. However, besides primary iodine deficiency, the goitre may probably develop due to effects of other bioelement imbalances, essential to thyroid function maintenance. Here we studied 44 cases of endemic goitre in prepubertal children (7–10 y.o.) living in iodine-adequate territory. Thyroid volume was estimated by ultrasonometry. Main bioelements (Al, Ca, Cd, Co, Cr, Cu, Fe, Hg, I, Mg, Mn, Pb, Se, Si, Zn) were determined in hair samples by ICP-OES/ICP-MS method. Relationships between hair content of bioelements and thyroid gland size were estimated by multiple regressions. The regression model revealed significant positive relations between thyroid volume and Cr, Si, Mn contents. However, the actual factor of thyroid gland increase was only Si excess in organism. Significant negative relations of thyroid volume were revealed with I, Mg, Zn, Se, Co and Cd. In spite of this, the actual factors of thyroid gland volume increasing were I, Co, Mg and Se deficiency. Total bioelement contribution in thyroid impairment was estimated as 24%. Thus, it was suggested that endemic goitre in iodine-adequate territory can be formed by bioelement imbalances, namely Si excess and Co, Mg, Se shortage as well as endogenous I deficiency in spite of iodine-adequate environment.     

Antithyroid autoantibodies in the examined population with iodine prophylaxis after the Chernobyl catastrophe

The aim of the present study was the observation of the frequency of antithyroid autoantibodies in the population in low endemic goitre area after mass iodine prophylaxis after the Chernobyl catastrophe and the estimation of TSH and thyroid hormones secretion in this population. On the basis of the investigations carried out we could conclude that the frequency of antithyroid autoantibodies in the population with confirmed endemic goitre is comparable to the frequency of antithyroid autoantibodies in the healthy population. ATA occurrence in children after iodine prophylaxis could confirm the hypothesis that thyroglobulin immunity is higher after iodine intake. The lower T3 concentration observed in the group with antithyroid autoantibodies suggests that autoantibodies may be involved in the thyroid hormones synthesis or peripheral conversion of thyroid hormones.     

The effectiveness of a 40-year long iodine prophylaxis in endemic goitre region of Grobnik, Croatia

The region of Grobnik, in the north west of Croatia, 15 km away from the Adriatic coast and 400 meters above the sea level, used to be known as a centre of endemic goitre. Iodine prophylaxis of 10 mg KJ added per kilo salt started in Croatia during the year 1953 and it was increased to 25 mg KJ per kilo in 1996. During 1961, the prevalence of goitre among Grobnik school children was 63%, while in the adult population it was 34%. In 1981, 18% of goitrous school children and 11% of goitrous adults were found in the same region, which shows the fall in goitre prevalence in the twenty-year period, from a severe to a mild one. The aim of this study was to estimate the effectiveness of iodine prophylaxis in goitre eradication and to compare the obtained results to those found in the same region 20 and 40 years ago, namely, in 1961 and 1981. The research was conducted in 2001. We examined 472 Grobnik inhabitants, 378 children (196 girls and 182 boys, aged 7-15 years) and 94 adults. Regarding their size thyroid glands were graded according to WHO and PAHO classification. Data regarding lifestyles and health conditions were collected by individual and family questionnaires. The prevalence of goitre in 2001 was 6.6% in school children and 6.4% in adults. In relation to 1981, we found a statistically significant fall of goitre in school children at the level of p < 0.01 (chi2 = 23.65), but the prevalence change was not statistically significant in adults (p > 0.01, chi2 = 1.419). The frequency of thyroid gland hereditary diseases in native inhabitants was high, 11.7%. There were no statistically significant differences in the prevalence of goitre or thyroid hereditary diseases between groups of native and newcomers' children. According to our results, in the year 2001 the area of Grobnik was still was a region of a mildly expressed endemic goitre. This study presents final results of a 40-year long follow up of endemic goitre eradication, demonstrating the long-term effectiveness of iodine prophylaxis.     

The problem of goitre with particular consideration of goitre resulting from iodine deficiency (I): classification,diagnostics and treatment

In the present review paper, the following problems have been brought up: 1) types of nontoxic goitre and applied classification, 2) physiological periods or states predisposing to non-toxic goitre development, 3) evaluation of excessive stimulation of the thyroid gland, 4) the treatment of iodine deficiency consequences (non-toxic diffuse vs. non-toxic nodular goitre), 5) autoimmunologically-induced non-toxic goitre, and 6) positive effects of iodine prophylaxis with respect to goitre prevalence. The management of non-toxic nodular goitre, as well as of thyroid nodules is a separate and very complex issue, and--at the same time--the subject of our next review paper, published in the same issue of NEL.     

Role of iodine in antioxidant defence in thyroid and breast disease

The role played in thyroid hormonogenesis by iodide oxidation to iodine (organification) is well established. Iodine deficiency may produce conditions of oxidative stress with high TSH producing a level of H_2O_2, which because of lack of iodide is not being used to form thyroid hormones. The cytotoxic actions of excess iodide in thyroid cells may depend on the formation of free radicals and can be attributed to both necrotic and apoptotic mechanisms with necrosis predominating in goiter development and apoptosis during iodide induced involution. These cytotoxic effects appear to depend on the status of antioxidative enzymes and may only be evident in conditions of selenium deficiency where the activity of selenium containing antioxidative enzymes is impaired. Less compelling evidence exists of a role for iodide as an antioxidant in the breast. However the Japanese experience may indicate a protective effect against breast cancer for an iodine rich seaweed containing diet. Similarly thyroid autoimmunity may also be associated with improved prognosis. Whether this phenomenon is breast specific and its possible relationship to iodine or selenium status awaits resolution.     

Epidemiology and prophylaxis of endemic goitre in the Bwa village of Sirao (Mali)

A study was conducted in Mali, in some villages exposed to iodine deficiency disorders (IDD). To treat and, above all, prevent endemic goitre, Lipiodol UF was dispensed in two ways: by intra-muscular injection (475 mg I) or by oral administration (48 mg I to 240 mg I). In two cases, hormone levels regained normal values and thyroid hypertrophies regressed significantly. Nevertheless, the impact of the treatment on the size of the goitres seems to be in favour of injections; which is probably due to the fact that in the village which received Lipiodol UF per os, many goitres were nodular.     

Drifting continents and endemic goitre in northern Pakistan.

Although Baltistan, north east Pakistan, is in a region of iodine deficiency disorders, the distribution of goitre within the district, according to age and sex, has not been clearly defined. To establish the prevalence of the condition and to measure the reported difference in prevalence in the north and south of the district thyroid size was assessed in new patients attending the Aman clinic, Khapalu, and outlying areas between April and September from 1981 to 1986. Samples of potable water collected from villages were analysed for iodine (as iodide) concentrations in Britain. Population weighted prevalences were: in the north in males 20.4%, in females 28.1% and in the south in males 13.9%, in females 21.2%. There was an overall deficiency of iodine in the water (mean iodine (as iodide) concentrations (north) 11.0 nmol/l (1.4 micrograms/l), (south) 11.8 nmol/l (1.5 micrograms/l) (95% confidence interval -0.7 to 0.9). The differences followed the Main Karakoram Thrust, suggesting a geological goitrogen in the north, which might be minerals containing ions such as BF4- and SO3F-, and molybdenite and calcium, which are present in rocks in Baltistan. A new hypothesis for the genesis of endemic goitre is proposed--that is, that continents on crustal plates drift across the earth and collide, one plate sliding under the other and melting, giving rise to characteristic mineral assemblages in the overlying rocks. As the minerals weather out they enter the diet of the local population, where in the presence of iodine deficiency they produce or enhance iodine deficiency disorders. Despite the current iodised oil campaign by the Pakistani government with Unicef a long term working iodisation programme is still urgently needed.     

Endemic goitre and plasmatic levels of vitamins A and E in the school-children on the island of Krk, Croatia

A total of 1975 school-children on the island of Krk aged 7-19 years of life were included in this study. The purpose was to establish the goitre status and plasmatic level of vitamins A and E in the examined children with the enlarged thyroid gland. The goitre prevalence was 29.8%. The average plasmatic values of vitamins A and E in the children with enlarged thyroids were statistically significantly lower from the reference values. Mentioned goitre prevalence at the level of moderate and heavier endemic goitre speaks on behalf of alimentary iodine deficiency. But the goiter examinations suggested the idoine deficiency not to be the only etiological factor of goitre on the island of Krk. Lower average plasmatic values of vitamins A and E in the examined with the enlarged thyroids referred to this fact to a certain degree.     

硒缺乏与甲状腺激素代谢及功能

Ｉ型脱碘酶为含硒酶,缺硒时,该酶活性下降,使循环Ｔ４增高,外周组织Ｔ３水平下降。缺硒可加速甲状腺组织碘的耗竭,并加重某些缺碘的生物学效应,缺硒还可能与碘缺乏病的发生发展有关。以缺硒为主要病因的克山病存在甲状腺激素代谢异常,其心肌呼吸酶活性变化与缺碘引起的甲状腺功能低下相似,缺碘可缺硒引起的甲状腺激素代谢改变与克山病的发生可能有关。     

Aspiration cytology of Hashimoto's thyroiditis in an endemic area

Fine needle aspiration (FNA) plays a significant role in the diagnosis of thyroid lesions due to its simplicity and low cost. Hashimoto's thyroiditis (HT) is the second most common thyroid lesion next to endemic goitre diagnosed on FNA in iodine (I2) deficient areas. Data on its incidence, prevalence and clinicopathological features in I2 deficient areas is scanty compared to I2 sufficient areas. In the present study the patients presented with HT a decade earlier than reported in I2 sufficient areas. Presentation as a nodular thyroid is common. Diagnosis of HT is likely to be missed in smears showing cytological evidence of hyperplasia or abundant colloid. HT was concurrent in 20 cases of endemic goitre. Careful screening for Hurthle cell change and lymphocytic infiltration into follicular cells should be carried out. In equivocal cases multiple punctures and immunological investigations are helpful. In antibody-negative cases repeat FNA at follow-up is useful. Marked lymphocytic infiltration and Hurthle cell change may indicate a hypothyroid state but hormonal levels are required for clinical management.     

Molecular and cellular mechanisms of transepithelial iodide transport in the thyroid

Thyroid hormone is an essential regulator of developmental growth and metabolism in vertebrates. Iodine is a necessary constituent of thyroid hormone. Due to the scarcity and uneven distribution of iodine on the Earth's crust, the structure of the thyroid gland is adjusted to collect and store this element in order to secure a continuous supply of thyroid hormone throughout life. Still, disease resulting from hypothyroidism due to iodine deficiency is a global health problem, illustrating the great biological significance that iodine saving mechanisms have evolved. Iodide is accumulated together with prohormone (thyroglobulin) in the lumen of the thyroid follicles. The rate-limiting step of this transport is the sodium/iodide symporter located in the basolateral plasma membrane of the thyroid follicular cells. Iodide is also transferred across the apical plasma membrane into the lumen where hormonogenesis takes place. In this review, recent progress in the understanding of transepithelial iodide transport in the thyroid is summarized.     

The prevalence of goitre and cretinism in a population of the west Ivory Coast

Iodine deficiency is a major public health problem in developing countries. The main areas where goitre is prevalent have been identified, but the different degrees of severity and the populations affected have not. Most countries are now attempting to obtain reliable and more extensive data. A pilot study was carried out in the Ivory Coast in order to improve epidemiological knowledge of iodine deficiency and collect the information required to set up an elimination programme. The aim of this study was to assess the prevalence of goitre and cretinism and to measure the main biochemical indicators of thyroid function (T3, T4 and TSH). The study involved 1433 people identified from a census. The prevalence of goitre was 50.3%. There was a significant difference between the examined ethnic groups: 52.7% of the Yacouba and 28.6% of the non-Yacouba had goitre. The most affected age group was 15-45 year. The predominance of women demonstrated the susceptibility of women at child-bearing age to develop the condition. The prevalence of cretinism was approximately 1.5%. Through the assessment carried out using a grid of clinical indicators, it was possible to identify 10 cases of laboratory proven myxedematous cretinism due to hypothyroidism. The concentration of iodine in foodstuffs was below the limit of detection (< 7.5 micrograms/kg) and iodine could not be detected in the water (< 1 microgram.l) The biological profile of the population was affected to a very limited extent, with a mean value (+/- standard deviation) for TSH of 1.93 (+/- 1.56) mIU/l (0.1-4.0) and a free T4 value of 10 (+/- 3.46) pmol/l (8.2-20). These initial results confirm the high prevalence of endemic goitre and the low iodine content of the soil, water and food in the investigated region. The study will be complemented by a nutritional investigation to improve the understanding of iodine balance, after which an appropriate action plan will be proposed.     

Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed

Thyroid cancer in children and adolescents has to be considered as the most severe health consequence of a nuclear reactor emergency with release of radioiodine into the atmosphere. High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. However, there are controversies concerning thyroid cancer risk induced by radioiodine exposure in adults. Further, the interaction of nutritional supply of potassium iodide and radioiodine uptake as well as the interaction of radioiodine with certain drugs has not been addressed properly in existing guidelines and recommendations. How to proceed in case of repeated release of radioiodine is an open, very important question which came up again recently during the Fukushima accident. Lastly, the side effects of iodine thyroid blocking and alternatives of this procedure have not been addressed systematically up to now in guidelines and recommendations. These questions can be answered as follows: in adults, the risk to develop thyroid cancer is negligible. In countries, where nutritional iodine deficiency is still an issue, the risk to develop thyroid cancer after a nuclear reactor emergency has to be considered higher because the thyroid takes up more radioiodine as in the replete condition. Similarly, in patients suffering from thyrotoxicosis, hypothyroidism or endemic goitre not being adequately treated radioiodine uptake is higher than in healthy people. In case of repeated or continued radioiodine release, more than one dose of potassium iodide may be necessary and be taken up to 1 week. Repeated iodine thyroid blocking obviously is not harmful. Side effects of iodine thyroid blocking should not be overestimated; there is little evidence for adverse effects in adults. Newborns and babies, however, may be more sensitive to side effects. In the rare case of iodine hypersensitivity, potassium perchlorate may be applied as an alternative to iodine for thyroid blocking.     

Pigmentation and dysfunction of Gunn rat thyroid

The thyroid gland of homozygous Gunn rats is moderately enlarged and displays a brownish-black discoloration. Light microscopic examination discloses that the follicular cells are filled with brown granules, which are shown, under the electron microscope, to be modified colloid droplets. Most of them possess a strong acid phosphatase and a mild peroxidase activity and contain a melanin-like pigment, according to histochemical analysis. In comparison with normal Wistar rats, Gunn rats possess significantly higher plasma thyroxine and lower triiodothyronine as well as an increased plasma TSH level. The soluble protein content of the thyroid is reduced in the Gunn rat, as is the total intrathyroid iodine content. The hyperthyroxinaemia of homozygous Gunn rats is due to a hereditary deficiency in hepatic glucuronyl transferase activity. The excess circulating thyroxine is of little functional importance because it is firmly bound to plasma proteins. But Gunn rats have a slight hypothyroid goitre for reasons not yet elucidated. The functional as well as morphological data at present available suggest a modified thyroid iodine metabolism and an altered composition of the thyroglobulin which may induce abnormalities in colloid proteolysis. The observed pigment may result from peroxidation of tyrosine. These alterations are probably independent of the sole enzymatic deficiency so far encountered in these animals and may probably be ascribed to a primary enzymatic defect in the thyroid gland itself.     

Endemic goiter, thiocyanate overload, and selenium status in school-age children

Iodine deficiency (ID) and related disorders are still major, yet unresolved health concerns. Recently, in a systematic survey of schoolage children (SAC), we reported severe to moderate ID, in Ankara and three cities from Black Sea region of Turkey. The current study attempted to evaluate selenium (Se) status, thiocyanate (SCN⁻) overload, and their possible contribution to the goiter endemics and thyroid hormone profile observed in these cities. Thyroid ultrasonography was performed and serum Se, SCN⁻, thyroid hormones, sensitive TSH (sTSH) levels, and urinary iodine concentrations (UICs) were determined from 251 SAC (9–11 yr old). Thyroid volumes (TVs) exceeding recommended upper normal limits and median UIC indicated goitre endemics and moderate to severe ID in the areas studied. Mean serum SCN⁻ concentrations were found to be greater than the controls from the literature. The UIC/SCN⁻ ratio was found to be lowest in Bayburt and Trabzon denoting that SCN⁻ overload may contribute to the goiter endemics. Serum Se concentrations represent a marginal deficiency in the four areas studied. No significant correlations between serum Se concentrations and the other parameters studied (i.e., TV, SCN⁻, thyroid hormones, sTSH, UIC) was detected. In conclusion, this study showed that selenium is also marginally deficient in the iodine-deficient endemic areas studied, but this has little or no impact on the thyroid hormone profile and the goiter endemics. SCN⁻ overload may contribute to the endemics, especially for the areas where iodine is severely deficient. An effective iodine supplementation program will not only resolve the goiter endemics but also the consequence of SCN⁻ overload as well in the endemic goiter areas studied.     

Selenium and thyroid function in infants, children and adolescents

Selenium is an integral component of the enzymes glutathione peroxidase (GPx) and iodothyronine deiodinases. Although selenium nutrition could conceivably affect thyroid function in infants, children and adolescents, available data suggest that the effect of selenium deficiency on thyroid function is relatively modest. In patients with isolated selenium deficiency (such as patients with phenylketonuria receiving a low-protein diet), peripheral thyroid hormone metabolism is impaired but there are no changes in thyrotropin (TSH) or clinical signs of hypothyroidism, suggesting that these patients are euthyroid. Selenium supplementation may be advisable to optimize tissue GPx activity and prevent potential oxidative stress damage. In areas where combined selenium and iodine deficiencies are present (such as endemic goiter areas in Central Africa), selenium deficiency may be responsible for the destruction of the thyroid gland in myxoedematous cretins but may also play a protective role by mitigating fetal hypothyroidism. In these areas, selenium supplementation should only be advocated at the same time or after iodine supplementation. In patients with absent or decreased production of thyroid hormones and who rely solely on deiodination of exogenous L-thyroxine for generation of the active triiodothyronine (such as patients with congenital hypothyroidism), selenium supplementation may optimize thyroid hormone feedback at the pituitary level and decrease stimulation of the residual thyroid tissue.     

Endemic cretinism in a traditional society in Mali: from the collectivity to the individual

The prevalence of endemic cretinism was measured in a village belonging to the Bwa ethnic group in Mali liable to iodine deficiency and suffering from endemic goitre. In this village according to mental and motor handicaps found in cretinism, we used two psychometric tests: the Raven's Progressive Matrice (PM 47) and a "peg test". Using the fiduciary inference method on the two tests associated with a clinical and qualitative approach, we obtained a prevalence of myxedematous cretinism close to 1.2%.     

Therapy of endemic goitre: controlled study on the effect of iodine and thyroxine

Two kinds of medical treatment of endemic goitre (400 microgram of iodine, n=11, and 150 microgram of L-thyroxine, n=12) were compared in a double blind study with a placebo group (n=12) during a period of 12 months and an observation time of three months after cessation of therapy. The means of the neck circumference and of the estimated thyroid volume decreased significantly during treatment in both groups, whereas no significant difference was observed in the placebo group. The results in both therapy groups did not differ significantly from each other. No side effects or symptoms of hyperthyroidism were observed. During treatment the index of free thyroxine (FT4I) increased significantly in both the iodine and the thyroxine group and delta TSH after TRH decreased significantly. Total triiodothyronine (TT3) did not show significant alterations. Three months after cessation of therapy in the thyroxine treated group the mean FT4I dropped into the range before treatment, whereas it remained slightly elevated in the iodine group. In the thyroxine treated group the mean delta TSH was higher than its value before therapy. After withdrawal of iodine, however, the mean delta TSH remained decreased for three months. The study indicates that 400 micrograms of iodine per day may be at least as effective as a standard dose of 150 micrograms of thyroxine to treat endemic goitre in an iodine deficient area.     

Fetal and maternal thyroid hormones

It is well known that insufficient production of thyroid hormones during the fetal and neonatal period of development may result in permanent brain damage unless treatment with thyroid hormone is instituted very soon after birth. But congenital hypothyroidism is not the only situation in which brain damage may be related to insufficient thyroid function. Cretinism is the most severe manifestation of iodine deficiency disorders found in areas where iodine intake is greatly reduced. Some of the manifestations of cretinism suggest that the insult to the developing brain starts earlier than in the case of congenital hypothyroidism. Hypothyroxinemia of mothers with adequate iodine intake may also leave permanent, though less severe, mental retardation. For these reasons the possible role of maternal transfer of thyroid hormones during early fetal development have been reinvestigated, using the rat to obtain various experimental models. It has been shown that thyroid hormones are found in embryonic tissues before onset of fetal thyroid function and that thyroidectomy of the mother results in delayed development of the concepta. The concentrations of T4 and T3 in embryonic tissues from thyroidectomized dams were undetectable before the onset of fetal thyroid function, and still reduced in some tissues near term, despite the onset of fetal thyroid function. Treatment of control and thyroidectomized dams with methyl-mercaptoimidazole to block fetal thyroid function reduced thyroid hormone concentrations in fetal tissues near term, but this decrease could be partially avoided by infusion of physiological doses of thyroxine to the mothers. Iodine deficiency of the mothers resulted in thyroid hormone deficiency of the developing embryo, which was very marked until term in all tissues including the brain. The results strongly support a role of maternal thyroid hormones in fetal thyroid hormone economy both before and after the onset of the fetal thyroid function, at least in the rat. They also support a role of the hypothyroxinemia of iodine-deficient mothers in initiating the brain damage of the endemic cretin, a damage which would not be corrected once the fetal thyroid becomes active, as iodine-deficiency of the fetus would impair adequate production of hormones by its own thyroid, and maternal transfer would continue to be low.     

Skeletal manifestations of hypothyroidism from Switzerland

Hypothyroidism is caused by a deficiency in the synthesis of thyroid hormone. Dwarfism is the most obvious skeletal manifestation, but most people with hypothyroidism do not have any skeletal evidence of the disease. When the skeleton is affected, the severity of this manifestation depends on the degree of the deficiency and age of onset. Endemic hypothyroidism typically is linked to specific ecological settings such as the high mountains where iodine is absent, or else it occurs with very low concentrations in water and soil. In these areas, the prevalence may be as high as 8%. The disease can be expected to occur in archaeological human skeletal samples from endemic regions. Sporadic hypothyroidism is caused by a deficiency in the thyroid gland itself, and is not linked to any specific environmental context. The disease may be the result of a genetic defect, but can also be caused by other pathological conditions that may affect the thyroid gland, including infection and cancer. The skeletal abnormalities of the two variants will be indistinguishable in archaeological human remains. In order to identify hypothyroidism in archaeological skeletal samples, one must be aware of the differences in pathological skeletal changes seen in hypothyroidism in comparison with other diseases, such as achondroplasia, that can cause similar abnormalities. Twelve clinically documented cases of hypothyroidism provide data for understanding the skeletal abnormalities associated with this disease. All 12 are modern documented cases from Switzerland, where endemic hypothyroidism occurred in the iodine-deficient Alpine regions. However, at least one case in the sample was caused by a defect in the thyroid gland itself.