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1.
Chinese Journal of Practical Internal Medicine ; (12): 311-315, 2019.
Artigo em Chinês | WPRIM | ID: wpr-816019

RESUMO

After more than 20 years of mandatory salt iodination program, what changes have taken place in the spectrum and prevalence of thyroid diseases? Recent national survey data show that the prevalence of most thyroid diseases(including clinical hyperthyroidism,subclinical hyperthyroidism, clinical hypothyroidism, autoimmune thyroiditis, and goiter) has not increased compared with the results of the 1999 survey. Only the prevalence of subclinical hypothyroidism and thyroid nodules increased.The increase of subclinical hypothyroidism is related to the increase of TSH reference value. No increased thyroid nodules have been found to be associated with increased iodine intake.Thyroid cancer rates have risen sharply, but increased iodine intake cannot be blamed. Studies have shown that iodine deficiency poses a greater risk of thyroid disease than excess iodine.The policy of iodizing salt should be continued.

2.
Chinese Medical Journal ; (24): 2143-2149, 2019.
Artigo em Inglês | WPRIM | ID: wpr-774646

RESUMO

BACKGROUND@#Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age.@*METHODS@#Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women's data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin 150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders.@*RESULTS@#The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ = 10.264, P = 0.002; 6.25% vs. 3.70%, χ = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241-3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011-3.282, P = 0.046, respectively).@*CONCLUSION@#ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.@*CLINICAL TRIAL REGISTRATION@#ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

3.
Chinese Medical Journal ; (24): 2143-2149, 2019.
Artigo em Inglês | WPRIM | ID: wpr-802921

RESUMO

Background@#Thyroid autoimmunity (TAI) is prevalent among women of reproductive age and associated with adverse pregnancy outcomes. This study aimed to investigate the association between iron nutritional status and the prevalence of TAI in women during the first trimester of pregnancy and in non-pregnant women of childbearing age.@*Methods@#Cross-sectional analysis of 7463 pregnant women during the first trimester of pregnancy and 2185 non-pregnant women of childbearing age nested within the sub-clinical hypothyroid in early pregnancy study, a prospective collection of pregnant and non-pregnant women’s data, was conducted in Liaoning province of China between 2012 and 2015. Serum thyrotropin, free thyroxine, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), serum ferritin, and urinary iodine were measured. Iron deficiency (ID) was defined as serum ferritin <15 μg/L and iron overload (IO) was defined as ferritin >150 μg/L. TPOAb-positive was defined as >34 U/mL and TgAb-positive was defined as >115 U/mL. Multilevel logistic regression was conducted to examine the association between TAI and different iron nutritional status after adjusting for potential confounders.@*Results@#The prevalence of isolated TPOAb-positive was markedly higher in women with ID than those without ID, in both pregnant and non-pregnant women (6.28% vs. 3.23%, χ2 = 10.264, P = 0.002; 6.25% vs. 3.70%, χ2 = 3,791, P = 0.044; respectively). After adjusting for confounders and the cluster effect of hospitals, ID remained associated with TPOAb-positive in pregnant and non-pregnant women (odds ratio [OR]: 2.111, 95% confidence interval [CI]: 1.241–3.591, P = 0.006; and OR: 1.822, 95% CI: 1.011–3.282, P = 0.046, respectively).@*Conclusion@#ID was associated with a higher prevalence of isolated TPOAbs-positive, but not with isolated TgAb-positive, in both pregnant women during the first trimester of pregnancy and non-pregnant women of childbearing age, while IO was not associated with either isolated TPOAb-positive or isolated TgAb-positive.@*Clinical trial registration@#ChiCTR-TRC-13003805, http://www.chictr.org.cn/index.aspx.

4.
Biomedical and Environmental Sciences ; (12): 932-937, 2017.
Artigo em Inglês | WPRIM | ID: wpr-311327

RESUMO

Iodine deficiency (ID) during early pregnancy has an adverse effect on children's psychomotor and motor function but the mechanism has not been clarified. Therefore, our aim was to study the effect of maternal marginal ID on cerebellar neurodevelopment and the underlying mechanism. After obtaining marginal ID rats, we examined interactions between Bergmann glia cells (BGs) and Purkinje cells (PCs) using immunofluorescence and expression of the glutamate transporter and receptor by western blot. Our results showed that marginal ID reduced the number of contacted points between BGs and PCs, and disturbed expression of the glutamate transporter and receptor. Our results support the hypothesis that marginal ID inhibits interactions of BGs-PCs, which may be involved in abnormal regulation of the glutamate transporter and receptor.

5.
Chinese Journal of Epidemiology ; (12): 53-56, 2007.
Artigo em Chinês | WPRIM | ID: wpr-261651

RESUMO

<p><b>OBJECTIVE</b>To investigate the effect of cigarette smoking on thyroid gland volume, thyroid function and thyroid autoantibodies in the areas with different iodine intakes.</p><p><b>METHODS</b>A cross-sectional epidemiological study in Panshan (mild iodine-deficient area), Zhangwu (more than adequate iodine intake area) and Huanghua (iodine-excessive area) was conducted in 3761 subjects in 1999.80.2 % of them were followed up in 2004. Questionnaires, thyroid function, thyroid autoantibodies, urinary iodine concentration,and thyroid B ultrasound were performed.</p><p><b>RESULTS</b>The prevalence of goiter was higher in smokers than in non-smokers (15.1% vs. 11.5%, P< 0.05). The average thyroid volume was higher in smokers with phenomenon more obvious in Panshan and Huanghua areas. Data from logistic analysis showed that smoking cigarette was an independent risk factor of goiter. There was no difference in serum TSH and Tg level between smokers and non-smokers. The positive rate of TPOAb (>100 IU/ml) was higher in smokers than in non-smokers(10.8% vs. 9.0 % , P <0.05) and was especially obvious in Huanghua area. Smoking was a independent risk factor of increasing positive rate of TPOAb. During the prospective observation,it was found that the incidence of positive TPOAb(>,100 IU/ml) was 7.4% in the subjects that were from non-smokers turning to smokers and 2.9% in those whose smoking behavior did not change. Logistic analysis indicated that the shifting from non-smoking to smoking was independent risk factor for the increase on high incidence of positive TPOAb.</p><p><b>CONCLUSION</b>Smoking cigarette was a independent risk factor of goiter. Smoking was also a risk factor of increasing TPOAb positive rate. Shifting from not smoking to smoking was an independent risk factor of increasing high incidence of positive TPOAb.</p>


Assuntos
Feminino , Humanos , Masculino , Autoanticorpos , Sangue , Estudos Transversais , Bócio , Sangue , Epidemiologia , Alergia e Imunologia , Incidência , Fumar , Testes de Função Tireóidea , Glândula Tireoide , Hormônios Tireóideos , Sangue
6.
Chinese Journal of Epidemiology ; (12): 25-28, 2005.
Artigo em Chinês | WPRIM | ID: wpr-232141

RESUMO

<p><b>OBJECTIVE</b>Impact of climate warming in winter on the potential epidemics of dengue fever in Hainan was assessed.</p><p><b>METHODS</b>Based on historic data of mean monthly temperature in January from 8 weather observation stations, tendency and amplitude of variation were analyzed. Using 21 degrees C as lowest limit of temperature suitable for dengue fever transmission, impact caused by climate warming on dengue fever epidemic was estimated by means of geography information system (GIS), insect vector and epidemiological features.</p><p><b>RESULTS</b>Temperature in winter in Hainan province had shown an obvious increase. The maximum amplitude of increase appeared in Dongfang which was 1.4 degrees C and the minimum 0.5 degrees C in Shanhudao, but the increase amplitude in the other stations was varied from 0.7 to 1.3 degrees C. By the year of 2050, 21 degrees C contour will have moved 190 km or so northward, nearly spanned 6/7 of distance from south to north in Hainan province and under the condition of daily fraction surviving of Aedes aegypti as P = 0.89, Qionghai city which stands north in Hainan province will probably have become epidemic area of dengue fever all year round.</p><p><b>CONCLUSION</b>Climate warming in winter will probably make half or more of the areas in Hainan province with temperature that permitting transmission of dengue fever by 2050. Monitoring and prevention of dengue fever in winter should be emphasized.</p>


Assuntos
Animais , Humanos , Aedes , Fisiologia , Virologia , China , Epidemiologia , Clima , Dengue , Epidemiologia , Vírus da Dengue , Sistemas de Informação Geográfica , Insetos Vetores , Virologia , Estações do Ano , Temperatura
7.
Chinese Medical Sciences Journal ; (4): 202-205, 2005.
Artigo em Inglês | WPRIM | ID: wpr-305422

RESUMO

<p><b>OBJECTIVE</b>To assess the relationships between iodine biological exposure and subclinical thyroid dysfunctions.</p><p><b>METHODS</b>The cross-sectional survey was performed to obtain the epidemiologic data of population in three communities with different iodine biological exposure: mild iodine deficiency [median urinary iodine concentration (MUI) of 50-99 microg/L], more than adequate iodine intake (MUI of 200-299 microg/L), and excessive iodine intake (MUI over 300 microg/L). Univariate and multivariate analysis (logistic regression analysis) were used to analyze the risk factors of subclinical hypothyroidism and subclinical hyperthyroidism.</p><p><b>RESULTS</b>Logistic regression analysis with sex and age controlled suggested that more than adequate iodine intake (OR = 3.172, P = 0.0004) and excessive iodine intake (OR = 6.391, P = 0.0001) increased the risk of subclinical hypothyroidism, while excessive iodine intake decreased the risk of subclinical hyperthyroidism (OR = 0.218, P = 0.0001). Logistic regression analysis including interaction of iodine intake and antibodies [thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb)] suggested that excessive iodine intake was an independent risk factor of subclinical hypothyroidism (OR = 6.360, P = 0.0001), but independent protect factor of subclinical hyperthyroidism (OR = 0.193, P = 0.0001). More than adequate iodine intake and it's interaction with TgAb increased the risk of subclinical hypothyroidism independently, in addition, it decreased the risk of subclinical hyperthyroidism at the present of TPOAb.</p><p><b>CONCLUSION</b>Both excessive iodine intake and more than adequate iodine intake could increase risk of subclinical hypothyroidism, supplement of iodine should be controlled to ensure MUI within the safe range.</p>


Assuntos
Adulto , Feminino , Humanos , Masculino , Autoanticorpos , Sangue , China , Estudos Transversais , Relação Dose-Resposta a Droga , Hipertireoidismo , Epidemiologia , Metabolismo , Hipotireoidismo , Epidemiologia , Metabolismo , Iodeto Peroxidase , Alergia e Imunologia , Iodo , Urina , Análise Multivariada , Fatores de Risco , Inquéritos e Questionários , Tireoglobulina , Alergia e Imunologia
8.
Chinese Medical Journal ; (24): 1518-1522, 2004.
Artigo em Inglês | WPRIM | ID: wpr-291888

RESUMO

<p><b>BACKGROUND</b>Reports are increasingly appearing on the side effects caused by excessive iodine intake. Our objective was to find out whether iodine excess would impair the thyroid function and intelligence of schoolchildren in rural areas of China.</p><p><b>METHODS</b>A comparative epidemiological study was made on thyroid function and intelligence of the schoolchildren in the areas of low, moderate or excessive intake of iodine. In the area of low intake of iodine (Panshan, Liaoning province, median urinary iodine (MUI) was 99 microg/L), of moderate intake of iodine (Zhangwu, Liaoning Province, MUI was 338 microg/L) and of excessive intake of iodine (Huanghua, Hebei Province, MUI was 631 microg/L). The numbers of schoolchildren from each area selected to take part in a Chinese version of Raven's Test were 190, 236 and 313, respectively, and then 116, 110 and 112 of them were tested for thyroid function, thyroid autoantibody (TAA) and urinary iodine (UI).</p><p><b>RESULTS</b>There were no significant differences in the incidences of overt hyperthyroidism, subclinical hyperthyroidism and overt hypothyroidism in Panshan, Zhangwu and Huanghua. But significant differences were found in the incidences of subclinical hypothyroidism (P = 0.001) in these three areas. The incidences of subclinical hypothyroidism in Huanghua and Zhangwu were 4.76 and 3.37 times higher than that in Panshan. TAA were negative in all the schoolchildren with subclinical hypothyroidism except for one. No significant difference was found among the rates of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in these three areas. Mean serum thyroglobulin (TG) value of Huanghua was markedly higher than those of the other two (P = 0.02). Mean serum TG value of Zhangwu was higher than that of Panshan but the difference was not significant. Mean IQ value of the schoolchildren in Huanghua was markedly higher than that for Zhangwu (P = 0.001). Mean IQ value of the schoolchildren in Panshan was lower than that of Huanghua and higher than that of Zhangwu but, again, the differences were not significant.</p><p><b>CONCLUSIONS</b>The increase of iodine intake may increase the risk for schoolchildren of subclinical hypothyroidism. In the area of iodine excess, most of the subclinical hypothyroidism cases are not of autoimmune origin. No obvious effect of excess iodine was found on mental development of schoolchildren.</p>


Assuntos
Criança , Feminino , Humanos , Masculino , Inteligência , Iodeto Peroxidase , Alergia e Imunologia , Iodo , Prevalência , Saúde da População Rural , Tireoglobulina , Alergia e Imunologia , Doenças da Glândula Tireoide , Epidemiologia , Tireotropina , Sangue
9.
Chinese Journal of Epidemiology ; (12): 575-577, 2004.
Artigo em Chinês | WPRIM | ID: wpr-247516

RESUMO

<p><b>OBJECTIVE</b>To assess the potential impact of warming climate in winter to the scale and severity of schistosomiasis epidemics in China.</p><p><b>METHODS</b>Based on the data of mean temperature and monthly minimum temperature in January from 126 (out of 733) weather observation stations in China, the trend and oscillation amplitude was analyzed. The impact of warming climate in winter to the scale of schistosomiasis spreading was assessed, using the indices of 0 degrees C mean temperature and -4 degrees C mean monthly minimum temperature in January. Correlation between these two indices was analyzed.</p><p><b>RESULTS</b>Evidences showed the warming climate in winter was seen all over China with the mean monthly minimum temperature and the mean temperature in January had increased 1.3 degrees C and 0.9 degrees C since 1986. The contours of mean monthly minimum temperature -4 degrees C and mean temperature 0 degrees C in January moved 1 - 2 latitudes northward.</p><p><b>CONCLUSION</b>The warming climate phenomenon seen in winter was considered favorable to the living of snails in winter, resulting in the possible increase of northward spreading of snails.Thus, monitoring of snails should be paid special attention.</p>


Assuntos
Animais , Feminino , Humanos , Masculino , China , Epidemiologia , Clima , Reservatórios de Doenças , Educação em Saúde , Prevalência , Schistosoma japonicum , Fisiologia , Esquistossomose Japônica , Epidemiologia , Estações do Ano , Caramujos , Parasitologia , Fisiologia , Temperatura
10.
Chinese Journal of Endocrinology and Metabolism ; (12)2000.
Artigo em Chinês | WPRIM | ID: wpr-676737

RESUMO

Objective To investigate the kinetic changes of inflammatory cell infiltration and thyroid autoantibodies in the development of iodine-induced autoimmune thyroiditis in NOD.H-2~(h4)mice.Methods Either 128 five-week-old NOD.H-2~(h4)mice or 128 Kunming mice were randomly divided into two groups,and received plain water or water containing 0.05% sodium iodide.At the time points of 1,2,4,8,12,16,and 24 week after receiving iodinated water,mice were anesthetized by diethyl ether and bled from eye socket vein,and their thyroid glands were collected.Indirect ELISA method was used to measure the levels of serum thyroglobulin autoantibodies (TgAb)and thyroid hormone.After being fixed with paraformaldehyde and embedded in paraffin,thyroid sections were stained with HE and used for morphometrieal analysis.Results In the iodine treated group of NOD.H-2~(h4) mice,autoimmune thyroiditis was observed as early as 1 week after they began receiving indinated water.The prevalence as well as the degree of autoimmune thyroiditis reached the maximum at 12 weeks and remained until 24 weeks.Serum TgAb level increased after 8 weeks of iodine ingestion in NOD.H-2~(h4) mice,then increased steadily throughout the 24 weeks of experiment.On the contrary,serum TgAb was not increased in the control group of Kunming mice.Conclusion Iodine may induce and exacerbate lymphocytic infiltration of the thyroid in genetically susceptible NOD.H-2~(h4) mice,and serum TgAb is just a marker of autoimmune thyroiditis.

11.
Chinese Journal of Endocrinology and Metabolism ; (12)2000.
Artigo em Chinês | WPRIM | ID: wpr-676249

RESUMO

Objective To perform a follow-up survey about thyroid disorders in three rural communities with different iodine intakes in China,observe the incidences and natural outcomes of positive thyroid autoantibodies in euthyroid population,and also explore the influence of iodine intakes on these outcomes and autoantibodies.Methods In 1999,a cross-sectional study on thyroid disorders was performed in three rural communities of Pansan ( mild iodine deficient area),Zhangwu ( more than adequate iodine intake area) and Huanghua (excessive iodine intake area) in China.The 5-year follow-up study was performed in 2004.Both in 1999 and 2004,serum levels of TSH,thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were measured with the same method.Iodine in urine and B ultrasound on thyroid were also examined.Results Among the euthyroid subjects with normal TSH level in 1999,an increased prevalence of positive TPOAb in Zhangwu and an increased prevalence of positive TgAb in Hnanghua were observed in 2004 (both P<0.05 ).Most of euthyroid subjects with positive TPOAb or positive TgAb in 1999 remained positive thyroid antibodies in 2004. The percentage was even higher in those with high levels of antibodies.Thyroid dysfunction was more frequent in subjects with positive TPOAb and/or TgAh than in those without thyroid antibodies (14.44% vs 3.11%,P<0.01).For those with positive antibodies in 1999,the incidence of hypothyroidism in 2004 was 1.32%,8.46% and 15.38% in Pansan,Zhangwu and Huanghua,respectively (P<0.05).The 5-year cumulative incidences of positive TPOAb (≥50 U/ml) and TgAb (≥40 U/ml) were 2.81% and 3.82%,respectively.The incidence of positive TPOAb was the highest in Zhangwu ( 3.84% ).The incidence of positive TgAb was the highest in Huanghua (5.07%),significantly higher than those in other two areas (P<0.05).Conclusion The incidence of thyroid dysfunction is higher in subjects with positive antibodies than that in those with negative antibodies.The high iodine intake is a risk factor of hypothyroidism in subjects with positive thyroid antibodies.Sustained excessive iodine intake increases the incidence of positive thyroid antibodies.

12.
Chinese Journal of Endocrinology and Metabolism ; (12)2000.
Artigo em Chinês | WPRIM | ID: wpr-676248

RESUMO

Objective To analyze the relationship between different iodine intakes and epidemiological features of hyperthyroidism in 3 communities with different iodine intake levels,as well as to explore the risk factor for the pathogenesis of hyperthyroidism.Methods A cohort study was performed in 3 Chinese rural communities with long-term stable iodine nutrition status defined as mild deficient (Panshan),more than adequate (Zhangwu, previously mild iodine deficiency and salt iodization lasting 8 years until 2004) and excessive (Huanghua).A total of 3 761 (934 males,2 827 females) inhabitants aged above 13 participated in the original investigation in 1999 and 3 018(709 males,2 309 females) of them received identical examinations after 5 years.Results Median urinary iodine concentration of school-aged children was 87.61zg/L in Panshan,213.9?g/L in Zhangwu and 633.5?/L in Huanghua (P<0.05) at fallowing up,and no statistic significance was found when comparing the corresponding data from original survey (83.5?g/L,242.9?g/L and 650.9?g/L).The accumulative incidence of hyperthyroidism was 13.6/1 000,9.4/1 000 and 8.1/1 000 (P>0.05),being 16.4/1 000,11.2/1 000 and 9.1/1 000 (P>0.05) in female,respectively in Panshan,Zhangwu and Huanghua.In original healthy subjects (without history of thyroid disease and overt thyroid dysfunction) merely with either positive thyroid peroxidase antibody (TPOAb>50 IU/ml) or thyroglobulin antibody (TgAb>40 IU/ml),the accumulative incidence of newly diagnosed hyperthyroidism was not significantly different among 3 communities in follow-up survey.TSH<0.3 mIU/L,positive TPOAb or goiter in original healthy participants were associated with the occurrence of overt hyperthyroidism in 5 years [ Logistic Regression,OR = 5.7 (95% CI 2.1-15 ),OR = 3.8 (95% CI 1.7-8.7 ) and OR = 3.1 (95% CI 1.4-6.8) respectively].Conclusion Iodine supplementation in mild iodine deficient area does not increase the incidence of overt hyperthyroidism ultimately.Long-term excessive iodine intake does not affect the incidence and pattern of hyperthyroidism.TSH<0.3 mIU/L,positive TPOAb and goiter in healthy individuals are the risk factors for hyperthyroidism.

13.
Chinese Journal of Endocrinology and Metabolism ; (12)2000.
Artigo em Chinês | WPRIM | ID: wpr-676247

RESUMO

Objective To investigate epidemiologieal characteristics of hypothyroidism and factors influencing its outcome in the areas with different iodine intakes.Methods An epidemiologic follow-up study of thyroid diseases was performed in Panshan (iodine deficient),Zhangwu [mild iodine deficiency before universal salt iodination (USI) and more than adequate iodine intakes after USI ] and Huanghua ( iodine excessive) in China.A total of 3 761 subjects were investigated in 1999,and 3 018 (80.2% ) of them were followed up in 2004.FT_4,FT_3,TSH,thyroid autoantibodies and urinary iodine concentration were determined and thyroid B ultrasound was performed in all participants.Results Five-year cumulative incidence of overt hypothyroidism was 0.23%,0.47% and 0.35% in Panshan,Zhangwu and Huanghua,respectively.Twenty patients with autoimmune- induced overt hypothyroidism did not comply with the physician's orders to take thyroxine.Thyroid function spontaneously turned to normal in 55% of them,turned to subclinical hypothyroidism in 20% and maintained overt hypothyroidism in 25%.Five-year cumulative incidence of subclinical hypothyroidism in Zhangwu (2.60%) and Huanghua (2.89%) were significantly higher than that in Panshan(0.23% ) (both P<0.01 ).One hundred patients with subclinical hypothyroidism were followed up,and 5% of them developed overt hypothyroidism,66% turned to euthyroidism and 29% maintained subclinical hypothyroidism.Raised serum TSH (>6 mU/L) in the original survey ( OR = 3.4),positive thyroid autoantibodies in the follow-up study ( OR = 5.3 ) and more than adequate iodine supplementation in the mild iodine-deficient population ( OR = 8.0) were risk factors influencing outcome of subclinical hypothyroidism.Conclusion More than adequate iodine supplementation among a population in the mildly iodine-deficient area may increase the incidence of overt and subolinical hypothyroidism, and also influence outcome of subclinical hypothyroidism.

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