RESUMEN
Recent identification of new selenocysteine-containing proteins has revealed relationships between the two trace elements selenium (Se) and iodine and the hormone network. Several selenoproteins participate in the protection of thyrocytes from damage by H(2)O(2) produced for thyroid hormone biosynthesis. Iodothyronine deiodinases are selenoproteins contributing to systemic or local thyroid hormone homeostasis. The Se content in endocrine tissues (thyroid, adrenals, pituitary, testes, ovary) is higher than in many other organs. Nutritional Se depletion results in retention, whereas Se repletion is followed by a rapid accumulation of Se in endocrine tissues, reproductive organs, and the brain. Selenoproteins such as thioredoxin reductases constitute the link between the Se metabolism and the regulation of transcription by redox sensitive ligand-modulated nuclear hormone receptors. Hormones and growth factors regulate the expression of selenoproteins and, conversely, Se supply modulates hormone actions. Selenoproteins are involved in bone metabolism as well as functions of the endocrine pancreas and adrenal glands. Furthermore, spermatogenesis depends on adequate Se supply, whereas Se excess may impair ovarian function. Comparative analysis of the genomes of several life forms reveals that higher mammals contain a limited number of identical genes encoding newly detected selenocysteine-containing proteins.
Asunto(s)
Sistema Endocrino/fisiología , Selenio/fisiología , Glándula Tiroides/fisiología , Animales , HumanosRESUMEN
Endemic myxoedematous cretinism has been associated with combined selenium and iodine deficiency in several areas of Zaire. To determine selenium and iodine status across the country, serum selenium and thyroid function parameters including urinary iodide were determined at prenatal clinics in 30 health centres of rural villages distributed over the whole country. Only in Bas-Zaire was the mean serum selenium level similar to that in non-deficient areas (80-120 ng/ml); in the regions of Bandunda and Kasai levels were marginally decreased (55-80 ng/ml), and in Kivu, Haut-Zaire, Equateur and Shaba they were marginally or moderately decreased (< 55 ng/ml). The frequency of abnormally low urinary iodide (< 5 micrograms/dl) varied from 20% in the region of Bas-Zaire to 50% in Kasai (P < 0.001), and to still higher percentages in the 5 other regions of Zaire (Bandundu, 57%; Kivu, 63%; Equateur, 72%; Shaba, 76%; Haut-Zaire, 84%). With the exception of Bas-Zaire, biochemical maternal hypothyroidism (serum TSH > 5mU/l) was present in every region, with a frequency ranging from 3% in Kivu to 12% in Equateur. Iodine deficiency affects most of the Zairean population and requires public health measures on a larger scale than previously estimated. Combined iodine and selenium deficiency affects Equateur, Haut-Zaire and Kivu, where endemic myxoedematous cretinism occurs, but also Shaba, where it was not previously described. Besides combined iodine and selenium deficiency which is permissive, another factor (thiocyanate?) must be taken into account to explain the peculiarly elevated prevalence of endemic myxoedematous cretinism in Central Africa.
Asunto(s)
Yodo/deficiencia , Embarazo/sangre , Selenio/sangre , Hipotiroidismo Congénito/etiología , República Democrática del Congo , Enfermedades Endémicas , Femenino , Bocio Endémico , Humanos , Yoduros/orina , Embarazo/orina , Salud Rural , Selenio/deficiencia , Hormonas Tiroideas/sangreRESUMEN
Free radical damage and fibrosis caused by selenium deficiency are thought to be involved in the pathogenesis of myxoedematous cretinism. So far, no pathway explains the link between selenium deficiency and tissue fibrosis. Pharmacological doses of iodine induce necrosis in iodine-deficient thyroids. Necrosis is much increased if the glands are also selenium-deficient, which then evolve to fibrosis. This rat model was reproduced to explore the role of selenium deficiency in defective tissue repair. At first, proliferation indexes of epithelial cells and fibroblasts were comparable between selenium-deficient and control groups. Then, in selenium-deficient thyroids the inflammatory reaction was more marked being mainly composed of macrophages. The proliferation index of the epithelial cells decreased, while that of the fibroblasts increased. These thyroids evolved to fibrosis. TGF-beta immunostaining was prominent in the macrophages of selenium-deficient rats. Anti TGF-beta antibodies restored the proliferation indexes, and blocked the evolution to fibrosis. In selenium deficiency, an active fibrotic process occurs in the thyroid, in which the inflammatory reaction and an excess of TGF-beta play a key role.
Asunto(s)
Macrófagos/fisiología , Selenio/deficiencia , Glándula Tiroides/patología , Factor de Crecimiento Transformador beta/fisiología , Animales , División Celular , Células Epiteliales , Femenino , Fibroblastos/citología , Fibrosis , Bocio/inducido químicamente , Inflamación , Macrófagos/química , Percloratos/farmacología , Ratas , Ratas Wistar , Compuestos de Sodio/farmacología , Yoduro de Sodio/farmacología , Glándula Tiroides/inmunología , Factor de Crecimiento Transformador beta/análisisRESUMEN
In Central Africa, all of northern Zaire is very severely deficient in iodine. A peculiar feature of this endemia is that iodine deficiency and the ensuing thyroid gland stimulation not only leads to goitre formation but also to progressive thyroid involution and to myxoedematous cretinism. An iodine supplementation trial based on oral administration of small doses of iodine was made in 81 schoolchildren. All of them received a small dose of iodine (0.1 ml containing 48 mg) per os and the thyroid status was followed during 4 months. Blood and urine samples were collected at the start of the study, then 2 weeks, 2 months and 4 months after iodine administration. Before iodine supplementation the mean urinary iodine level was 0.18 +/- 0.02 micromol/l, and 10% of the subjects had a urinary iodine level below 0.08 micromol/l. Fifty-two percent of the subjects had a serum thyrotropin (TSH) level above 10 mU/l. All the subjects responded to the administration of iodine. and all of them recovered a euthyroid status. Most of them were still euthyroid at the end of the study. However. within 4 or even 2 months, some subjects (15 % of the total) reverted to hypothyroidism. At the entry of the study these subjects were all hypothyroid and had elevated TSH and paradoxically low serum thyroglobulin (TG) values. In myxoedematous cretins living in the same area, even lower serum TG levels were found. Together with the absence of goitre, a paradoxically low serum TG Suggests a low thyroid reserve, and in the present case a reduced amount of functional thyroid tissue. We show that the serum TG/TSH ratio may be used as a predictive index of thyroid reserve and of positive response to iodine administration. These data further suggest that thyroid damage is not confined to myxoedematous cretins. but is widely distributed in the phenotypically normal population. Widely distributed thyroid damage may render iodine prophylaxis based on oral administration unpredictable.
Asunto(s)
Hipotiroidismo/sangre , Hipotiroidismo/tratamiento farmacológico , Aceite Yodado/uso terapéutico , Tiroglobulina/sangre , Hormonas Tiroideas/sangre , Tirotropina/sangre , Administración Oral , Adolescente , Análisis de Varianza , Niño , Hipotiroidismo Congénito/sangre , Femenino , Humanos , Aceite Yodado/administración & dosificación , Masculino , PalpaciónRESUMEN
It has been suggested that selenium deficiency is a co-factor to iodine deficiency in the pathogenesis of myxoedematous cretinism. The mechanism proposed is that the generation of hydrogen peroxide is greatly increased in iodine-deficient thyroid glands, and that selenium is involved in the control of hydrogen peroxide and its derived free radicals. This study was carried out to investigate the effect of the possibly impaired cellular defence mechanism associated with selenium deficiency on thyroid necrosis and tissue repair. For this purpose, we studied thyroid tissue from selenium- (SE-) and/or iodine-deficient (I-) rats before and after an acute toxic iodine overload. In I- thyroids, necrotic cells were numerous. Acute iodine administration increased this effect. Necrosis was associated with transient infiltration of inflammatory cells. In I-SE+ thyroids the tissue resumed its normal appearance. In I-SE- thyroid glands, the iodide toxicity was stronger, with greater necrosis and inflammatory reaction. The inflammation resolved but was replaced by fibrotic tissue. Fifteen days after the toxic overload, the connective tissue volume was twice the control value. Before iodide overload, the proportion of dividing cells was equal in I-SE+ and I-SE- thyroids. Three days after the iodide overload, this proportion was increased in I-SE+ thyroids but reduced in the I-SE- thyroids. Overall, the I-SE- thyroids had four times fewer dividing cells than the I-SE+ thyroids. In summary, selenium deficiency coupled to iodine deficiency increased necrosis, induced fibrosis and impeded compensatory epithelial cell proliferation. These results are compatible with histological and functional description of thyroid tissue from myxoedematous cretins.
Asunto(s)
Mixedema/etiología , Selenio/deficiencia , Glándula Tiroides/patología , Animales , División Celular/fisiología , Epitelio/metabolismo , Epitelio/patología , Femenino , Fibrosis , Radicales Libres , Bocio/etiología , Bocio/patología , Peróxido de Hidrógeno/metabolismo , Hiperplasia , Yodo/administración & dosificación , Yodo/deficiencia , Mixedema/patología , Mixedema/fisiopatología , Necrosis , Ratas , Ratas Wistar , Selenio/fisiología , Glándula Tiroides/metabolismo , Glándula Tiroides/fisiologíaAsunto(s)
Antitiroideos/efectos adversos , Hipotiroidismo Congénito/etiología , Yodo/deficiencia , Selenio/deficiencia , Animales , Asia/epidemiología , Hipotiroidismo Congénito/clasificación , Hipotiroidismo Congénito/epidemiología , Hipotiroidismo Congénito/fisiopatología , República Democrática del Congo/epidemiología , Conducta Alimentaria , Femenino , Enfermedades Fetales/etiología , Edad Gestacional , Humanos , Yodo/fisiología , Intercambio Materno-Fetal , Modelos Biológicos , Mixedema/epidemiología , Mixedema/etiología , Sistema Nervioso/embriología , Malformaciones del Sistema Nervioso , Nueva Guinea/epidemiología , Fenotipo , Embarazo , Complicaciones del Embarazo , Ratas , Selenio/fisiología , América del Sur/epidemiología , Glándula Tiroides/embriología , Glándula Tiroides/fisiopatología , Hormonas Tiroideas/metabolismo , Tirotropina/metabolismoRESUMEN
The effect of selenium deficiency associated with various iodide intake was investigated in rats in order to better understand its possible role in the etiopathogeny of myxedematous cretinism. Groups of rat pups were fed from birth a low selenium diet (Se-) and submitted to goitrogenic treatment (1% perchlorate in water) for one month. Some animals were refed iodide after perchlorate withdrawal. The gland morphology was analyzed in correlation with the glutathione peroxidase (GPX) activity and the thyroid hormone plasma levels. In all Se- rats, the GPX activity was strongly reduced as compared to selenium sufficient (Se+) animals (P < 0.01). Goitrous rats were hypothyroid whatever the selenium intake. After iodide refeeding, plasma T4 and T3 levels were increased by 160% in Se- rats and by respectively 330% and 580% in Se+ rats. The thyroid morphology was different according to the selenium intake: necrotic cells were about three times more numerous in Se- than in Se+ rats (P < 0.01) and the inflammatory reaction was increased. These experimental data demonstrate the detrimental role of selenium deficiency in one experimental case of thyroid disease. Such reduction of cell defences could contribute to the thyroid failure of African myxedematous cretins.
Asunto(s)
Yoduros/administración & dosificación , Yodo/deficiencia , Selenio/deficiencia , Glándula Tiroides/patología , Animales , Relación Dosis-Respuesta a Droga , Glutatión Peroxidasa/sangre , Yoduros/farmacología , Necrosis , Ratas , Ratas Wistar , Glándula Tiroides/efectos de los fármacos , Hormonas Tiroideas/sangreRESUMEN
Several hypotheses concerning consequences of selenium deficiency on iodine metabolism can be proposed on the basis of experimental studies in rats and from epidemiological and experimental studies in humans. By decreasing intracellular GSH peroxidase activity, selenium deficiency may increase hydrogen peroxide (H2O2) supply and lead over several weeks to the thyroid atrophy observed in myxoedematous cretins. By improving thyroid hormone synthesis and by decreasing peripheral thyroxin (T4) deiodination, selenium deficiency could protect fetal brain T4 supply and thus prevent neurologic cretinism. Selenium deficiency may protect against iodine deficiency by decreasing T4 metabolism--and thus iodide leakage and--perhaps also by increasing H2O2 supply and thyroid hormone synthesis and thus thyroid efficiency.
Asunto(s)
Selenio/deficiencia , Glándula Tiroides/metabolismo , Hormonas Tiroideas/metabolismo , Animales , Humanos , Peróxido de Hidrógeno/metabolismo , Yoduro Peroxidasa/metabolismo , Yodo/deficiencia , Selenio/uso terapéuticoRESUMEN
Studies were performed to assess the role of combined selenium and iodine deficiency in the etiology of endemic myxedematous cretinism in a population in Zaire. One effect of selenium deficiency may be to lower glutathione peroxidase activity in the thyroid gland, thus allowing hydrogen peroxide produced during thyroid hormone synthesis to be cytotoxic. In selenium-and-iodine-deficient humans, selenium supplementation may aggravate hypothyroidism by stimulating thyroxin metabolism by the selenoenzyme type I iodothyronine 5'-deiodinase. Selenium supplementation is thus not indicated without iodine or thyroid hormone supplementation in cases of combined selenium and iodine deficiencies.
Asunto(s)
Hipotiroidismo Congénito/etiología , Yodo/administración & dosificación , Yodo/deficiencia , Selenio/deficiencia , Tiroxina/deficiencia , Adolescente , Adulto , Niño , Preescolar , República Democrática del Congo , Glutatión Peroxidasa/sangre , Humanos , Lactante , Selenio/efectos adversos , Selenio/uso terapéutico , Tiroxina/sangreRESUMEN
OBJECTIVE: Severe selenium deficiency has been documented in northern Zaïre, already known as one of the most iodine deficient regions in the world and characterized by a predominance of the myxoedematous form of cretinism. This has been attributed to the double deficiency of essential trace elements. A short selenium supplementation programme was conducted in this area to evaluate the effects of a selenium supplementation on thyroid diseases. DESIGN: Placebo or selenium 50 micrograms as selenomethionine was administered once daily for 2 months. Blood and urine samples were collected before and after supplementation. PATIENTS: Fifty-two healthy schoolchildren from northern Zaire. MEASUREMENT: Selenium status, thyroid function and urinary iodide were determined. RESULTS: After 2 months of selenium supplementation, mean +/- SD serum T4 decreased from 73.1 +/- 45.4 to 48.3 +/- 23.7 nmol/l (P less than 0.001), serum FT4 from 11.8 +/- 6.7 to 8.4 +/- 4.1 pmol/l (P less than 0.01), and serum rT3 from 124 +/- 115 to 90 +/- 72 pmol/l (P less than 0.05), without significant change in serum T3 and serum TSH. CONCLUSION: Deiodinase type I which has been shown to be a seleno-enzyme could account for the changes in thyroid hormones in our subjects. Our data show that selenium plays a definite role in thyroid hormone metabolism in humans. Selenium could be an important cofactor in the clinical picture of iodine deficiency in Central Africa and could be involved in the aetiology of both forms of cretinism.
Asunto(s)
Yodo/deficiencia , Selenio/administración & dosificación , Selenio/deficiencia , Hormonas Tiroideas/sangre , Administración Oral , Humanos , Yodo/administración & dosificación , Selenio/sangre , Tiroxina/sangre , Triyodotironina/sangre , Triyodotironina Inversa/sangreRESUMEN
Severe goiter, cretinism, and the other iodine deficiency disorders (IDD) have their main cause in the lack of availability of iodine from the soil linked to a severe limitation of food exchanges. Apart from the degrees of severity of the iodine deficiency, the frequencies and symptomatologies of cretinism and the other IDD are influenced by other goitrogenic factors and trace elements. Thiocyanate overload originating from consumption of poorly detoxified cassava is such that this goitrogenic factor aggravates a relative or a severe iodine deficiency. Very recently, a severe selenium deficiency has also been associated with IDD in the human population, whereas in animals, it has been proven to play a role in thyroid function either through a thyroidal or extrathyroidal mechanism. The former involves oxidative damages mediated by free radicals, whereas the latter implies an inhibition of the deiodinase responsible for the utilization of T4 into T3. One concludes that: 1. Goiter has a multifactorial origin; 2. IDD are an important public health problem; and 3. IDD are a good model to study the effects of other trace elements whose actions in many human metabolisms have been somewhat underestimated.
Asunto(s)
Enfermedades Carenciales/etiología , Bocio Endémico/etiología , Yodo/deficiencia , Oligoelementos/deficiencia , Adolescente , Niño , Hipotiroidismo Congénito/epidemiología , Hipotiroidismo Congénito/etiología , Hipotiroidismo Congénito/metabolismo , Enfermedades Carenciales/epidemiología , Enfermedades Carenciales/metabolismo , República Democrática del Congo/epidemiología , Europa (Continente)/epidemiología , Femenino , Bocio Endémico/epidemiología , Bocio Endémico/metabolismo , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/etiología , Complicaciones del Embarazo/metabolismo , Estudios Prospectivos , Salud Pública , Selenio/deficiencia , Tiocianatos/envenenamientoRESUMEN
Selenium and seleno dependent glutathione peroxidase (GPX) deficiency has been described in endemias of myxedematous cretinism. In northern Zaire, a selenium supplementation trial has been conducted. Beside correcting the GPX activity, two months of selenium supplementation was shown to modify the serum thyroid hormones parameters in clinically euthyroid subjects and to induce a dramatic fall of the already impaired thyroid function in clinically hypothyroid subjects. These results further support a role of selenium in thyroid hormone metabolism. In an iodine deficient area, this selenium deficiency could lead to opposite clinical consequences: protect the general population and the fetus against iodine deficiency and brain damage; and in turn, favour the degenerative process of the thyroid gland leading to myxoedematous cretinism.
Asunto(s)
Hipotiroidismo/tratamiento farmacológico , Yodo/deficiencia , Selenio/efectos adversos , Niño , Hipotiroidismo Congénito/etiología , República Democrática del Congo , Glutatión Peroxidasa/metabolismo , Humanos , Hipotiroidismo/etiología , Hipotiroidismo/fisiopatología , Selenio/deficiencia , Selenio/uso terapéutico , Tirotropina/sangre , Tiroxina/sangre , Triyodotironina/sangreRESUMEN
Selenium status was determined in an endemic-goiter area and in a control area of Zaire. Compared with the reference values of a noniodine-deficient area, serum selenium in subjects living in the core of the northern Zaire endemic-goiter belt (Karawa villages) was seven times lower in 52 school-children and similarly low in 23 cretins; erythrocyte glutathione peroxidase (RBC-GPX) was five times lower in schoolchildren and still two times lower in cretins (P = 0.004). In a less severely iodine-deficient city of the same endemia (Businga), selenium status was moderately altered. RBC-GPX activity was linearly associated with serum selenium concentration up to a value of 1140 nmol/L and leveled off at approximately 15 U/g Hb at greater selenium concentration. At Karawa villages, selenium supplementation normalized both the serum selenium and the RBC-GPX. This combined iodine and selenium deficiency could be associated with the elevated frequency of endemic myxedematous cretinism in Central Africa.
Asunto(s)
Hipotiroidismo Congénito/etiología , Yodo/deficiencia , Selenio/deficiencia , Adolescente , Adulto , Análisis de Varianza , Niño , Preescolar , República Democrática del Congo , Eritrocitos/enzimología , Femenino , Glutatión Peroxidasa/sangre , Humanos , Hipotiroidismo/etiología , Masculino , Análisis de Regresión , Selenio/administración & dosificación , Selenio/sangreRESUMEN
Endemic goitre is accompanied by a spectrum of iodine deficiency disorders (IDD). From work undertaken by CEMUBAC in Ubangui Zaïre, the role of thiocyanate overload is recalled while this work demonstrates for the first time in man an action of selenium supplementation (and thus deficiency) on thyroid function in iodine deficient areas. The extreme severity of the selenium deficiency may intervene either on the central and/or peripheral deiodination of thyroxine, or on the synthesis of the thyroid hormones. Together with thiocyanate overload, selenium deficiency may be responsible of the high frequency of myxedematous cretins in Zaïre.