The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglo... more The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).
Objective: To determine the consumption of slimming pills (SP) and its asso- ciation with TSH lev... more Objective: To determine the consumption of slimming pills (SP) and its asso- ciation with TSH levels. Research Methods and Procedures: A survey was carried out in Rio de Janeiro (about 5 million inhabitants), Brazil, from June 2004 to April 2005. Households (1,500) were selected using three-stage probability sampling. Women were asked about use of SP, and blood sample was collect-
Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and sho... more Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Subjects and methods Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. Results We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Conclusions Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.
Arquivos brasileiros de endocrinologia e metabologia, 2009
Female steroid hormones deficiency leads to a significant increase in body mass, but the possible... more Female steroid hormones deficiency leads to a significant increase in body mass, but the possible central and peripheral mechanisms involved in increased food ingestion and fat accumulation in this situation are still unknown. In animal models, the specific lack of estrogen or its action produce progressive body mass gain, clearly demonstrating the possible role of this hormone in overweight after menopause. Obesity and overweight correspond to a relevant human health problem that can lead to premature death. Therefore unraveling the mechanisms underlying body mass gain is of great relevance, as well as the development of strategies to prevent its establishment. Energy balance regulation is associated with the control of body mass, and physical exercise is an important modulator of this homeostatic parameter. However, the influence of physical exercise in mass gain development during estrogen deficiency is controversial and depends on the exercise protocol used. In this study, we in...
Arquivos brasileiros de endocrinologia e metabologia, 2004
Thyroid hormone biosynthesis depends on iodide uptake and its incorporation into the acceptor pro... more Thyroid hormone biosynthesis depends on iodide uptake and its incorporation into the acceptor protein thyroglobulin (Tg), a high molecular weight protein secreted into the follicular lumen. The sodium-iodide symporter (NIS) is responsible for thyroid iodide uptake, the first step in thyroid hormonogenesis. Iodide is subsequently transported through the cellular membrane by pendrin (PDS) and then incorporated into Tg. Iodide oxidation and organification occur mainly in the thyrocyte apical surface and these reactions are catalyzed by thyroperoxidase (TPO) in the presence of hydrogen peroxide. Thus, thyroid iodide organification depends on TPO activity, which is modulated by the concentration of substrates (thyroglobulin and iodide) and cofactor (hydrogen peroxide). Hydrogen peroxide generation is catalyzed by the thyroid NADPH oxidase (ThOx), which is present in the apical pole of thyrocytes, is stimulated by thyrotropin and is inhibited by iodide. Hydrogen peroxide generation is the...
To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thic... more To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency (GHD), mean age 42.5 +/- 10.1 years, were studied and compared with 29 control subjects matched for sex, age, body mass index, and smoking habits. Lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein), serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the carotid arteries were performed at baseline and at 6, 12, and 24 months during GH therapy on maintenance dose. At baseline, when compared with the control group, patients presented increased carotid artery IMT (P < .05) and triglyceride levels (P < .001) and lower HDL concentrations (P < .01). In a linear regression analysis, age and known mean duration of GHD were correlated with carotid artery IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery IMT was observed (P < .01). The apolipoprotein B levels decreased significantly after the first 3 months of GH treatment (P < .001) and remained stable thereafter. Women also presented an increase in HDL cholesterol levels (P < .01). No differences were observed in the other lipids measured. Carotid artery IMT at baseline was inversely correlated with the change in carotid artery IMT (Delta = 24 months - baseline), r = 0.63, P < .001. In conclusion, 24 months of GH replacement therapy promoted favorable effects on carotid artery IMT and lipid profile in patients with GHD. Long-term follow-up studies are required to show whether these beneficial effects will result in reduction of morbidity and mortality from vascular disease.
This investigation evaluated and correlated clinical, laboratorial aspects and psychiatric sympto... more This investigation evaluated and correlated clinical, laboratorial aspects and psychiatric symptoms in sub clinical hypothyroidism (SH). Cross sectional study involving 103 patients with SH and 60 subjects without thyroid disease. Clinical and psychiatric evaluation was respectively based on the Zulewski score and Hamilton A, Hamilton D and Beck questionnaires. Serum thyreotropin (TSH), (thyroxine) FT4 and (antithyroperoxidase) ATPO were measured in all participants. Analysis of continuums data was assessed by the Student t- test, for normally distributed data, and by the Mann- Whitney and Kruskal Wallis tests for non-parametric data. The chi2, Fisher's and Kruskal Wallis tests were used to study qualitative variables. Multivariate analyses were used to study confounding variables. Mean serum TSH level was 7.76 +/- 2.9 micro UI/mL in SH and 1.66 +/- 0.6 micro UI/mL in the group without thyroid disease (p=0.001). Mean serum T4L was slightly lower among patients with HS, and showe...
International journal of pediatric endocrinology, 2010
Objectives. To evaluate, in children with Silver-Russell Syndrome, the response to the IGF-I and ... more Objectives. To evaluate, in children with Silver-Russell Syndrome, the response to the IGF-I and IGFBP-3 generation test and compare results to the growth response after 6 months of rhGH. Methods. Eight children (6 males), with a mean age of 5.71 ± 2.48 years and height SDS of -3.88 ± 1.28 received rhGH for 6 months. IGF-I and IGFBP-3 were analyzed before and after 4 doses of rhGH. Results. The mean growth velocity (GV) before treatment was 5.28 ± 1.9 cm/year. GV increased after rhGH in five children to a mean GV of 10.3 ± 3.64 cm/year. Six children had normal basal IGF-I levels and two low levels. After 4 doses of rhGH, the IGF-I levels were normal in seven. There was no correlation between the growth response and the IGF-I generation test. Conclusions. Children with SRS have normal IGF-I generation test. There is no correlation between the generation test and the growth velocity after 6 months of rhGH.
Arquivos Brasileiros De Endocrinologia E Metabologia, 2008
The amplifi cation of thyroglobulin (TG) mRNA in peripheral blood of patients with thyroid cancer... more The amplifi cation of thyroglobulin (TG) mRNA in peripheral blood of patients with thyroid cancer has been studied for almost one decade, but its real con- tribution for diagnosis of cancer relapse has not yet been established. In the present paper we report the case of a patient with papillary thyroid cancer with undetectable stimulated serum thyrogobulin levels after thyroid
European journal of endocrinology / European Federation of Endocrine Societies, 2014
Several studies have suggested an association between subclinical hypothyroidism (SCH) and increa... more Several studies have suggested an association between subclinical hypothyroidism (SCH) and increased cardiovascular risk. The aim of this study was to evaluate the presence of coronary artery disease (CAD) in asymptomatic patients with SCH by measuring the coronary artery calcium score (CACS). A total of 222 asymptomatic subjects (103 SCH and 119 euthyroid (EU)), who were between the ages of 35 and 65 years and had no previous history of CAD, were enrolled for this cross-sectional analysis. The criteria for SCH included a confirmed normal serum free thyroxine and high TSH levels. Lipid profile, Framingham risk score (FRS) and CACS analyses were performed for all subjects. The SCH and EU groups were comparable with respect to age, gender, BMI and frequency of diabetes, systemic arterial hypertension, hypercholesterolaemia and smoking. There was no difference in the median CACS between the SCH and EU groups. However, in the subgroup of subjects with intermediate/high FRS (AR10y ≥10%),...
Insulinomas ocultos são tumores não detectáveis aos exames convencionais. O estímulo superseletiv... more Insulinomas ocultos são tumores não detectáveis aos exames convencionais. O estímulo superseletivo arterial com cálcio e coleta venosa hepática (EACV) é um exame que pode ser utilizado para localizar o segmento pancreático acometido pelo tumor. Relatamos o caso de uma ...
Although well-differentiated thyroid carcinomas are usually curable by the combined effects of su... more Although well-differentiated thyroid carcinomas are usually curable by the combined effects of surgery, radioiodine ablation and thyroid stimulating hormone (TSH) suppressive therapy, recurrence develops in 20-40% of patients. During tumour progression, cellular de-differentiation occurs in up to 30% of cases and is usually accompanied by more aggressive growth, metastasis spread and loss of iodide uptake. The therapeutic options for de-differentiated thyroid cancer are limited and generally not efficient. Retinoic acids (RA) are biologically active metabolites of vitamin A that regulate growth and differentiation of many cell types, by binding to specific nuclear receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Recent studies have shown that RA can induce in vitro re-differentiation of thyroid carcinoma cell lines, as suggested by increased expression of the sodium/iodide symporter (NIS), type I iodothyronine deiodinase, alkaline phosphatase and by the increment of cellular (131)I uptake. In addition to re-differentiating effects, RA also exert anti-proliferative actions, as the inhibition of mitosis and the induction of apoptosis. Previous clinical studies have shown that iodide uptake may be re-stimulated after RA in about 20-50% of patients with radioiodine non-responsive thyroid carcinoma. Longer follow-up of patients demonstrated that, besides iodide uptake increment, RA can induce tumour regression or at least tumour growth stabilisation. The therapy is generally well tolerated and the most frequent side effects are dryness of skin and mucosa, and hypertriglyceridemia. This paper describes the recent advances in the field of thyroid cancer therapy and reviews the use of RA as a promising novel therapeutic tool.
The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglo... more The evaluation of patients with differentiated thyroid cancer is commonly based on serum thyroglobulin (Tg) measurement and 131I whole-body scan (WBS). The first follow-up (6-12 months after initial treatment) shows the response to therapy, a prognostic factor.The aims of the study were to describe the clinical outcome during a long-term follow-up of patients with negative 131I WBS in the first evaluation, and to assess clinical and histological characteristics related to the outcome in this patient population. This retrospective study reviewed data from 209 patients followed at 2 Brazilian hospitals. A minimum of 10 years of follow-up was required. During mean follow-up of 13.7 ± 4.2 years, 20% of patients developed recurrence. At the end of follow-up, 21% of patients had persistent disease. The clinical and histological characteristics related to adverse outcomes (recurrence or persistent disease) were lymph node metastases at diagnosis, high risk according to American Thyroid Association (ATA) classification, and incomplete response to treatment. Stimulated Tg levels (under thyroid hormone withdrawal) and basal Tg levels (with thyroid hormone) greater than 10 ng/mL at first evaluation were associated with an adverse outcome. Negative WBS at first evaluation should not be used as an isolated prognostic factor. This must be considered together with histopathological (ATA classification, lymph node metastases) and clinical/laboratory characteristics (stimulated and basal Tg; response to therapy).
Objective: To determine the consumption of slimming pills (SP) and its asso- ciation with TSH lev... more Objective: To determine the consumption of slimming pills (SP) and its asso- ciation with TSH levels. Research Methods and Procedures: A survey was carried out in Rio de Janeiro (about 5 million inhabitants), Brazil, from June 2004 to April 2005. Households (1,500) were selected using three-stage probability sampling. Women were asked about use of SP, and blood sample was collect-
Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and sho... more Objective Thyroid diseases are common in individuals with type 1 diabetes mellitus (T1DM) and should be investigated annually in these individuals. The aim of this study was to evaluate the frequency of thyroid diseases in first degree relatives (FDR) of patients with T1DM. Subjects and methods Eighty individuals (40 patients with T1DM and 40 FDR) were interviewed and blood was sampled for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroid peroxidase (TPO) antibodies measurement. Autoantibodies against glutamic acid decarboxylase 65 (GAD65), islet antigen-2 (IA2) and autoantibodies against insulin (AAI) were measured in FDR. Results We found a similar prevalence of thyroid dysfunction in patients with T1DM and their FDR (22.5% vs. 27.5%; p = 0,79). There were no differences in serum TSH levels (p = 0.29), FT4 (p = 0,45), frequency of abnormal TSH (p = 0.28), positive TPO antibodies (p = 0.13), titers of TPO antibodies (in positive cases) between patients with T1DM and their FDR (p = 0.94). Conclusions Thyroid abnormalities seem to be common not only in patients with T1DM but also in their FDR, which suggests that screening strategies for thyroid diseases might also be useful to these individuals.
Arquivos brasileiros de endocrinologia e metabologia, 2009
Female steroid hormones deficiency leads to a significant increase in body mass, but the possible... more Female steroid hormones deficiency leads to a significant increase in body mass, but the possible central and peripheral mechanisms involved in increased food ingestion and fat accumulation in this situation are still unknown. In animal models, the specific lack of estrogen or its action produce progressive body mass gain, clearly demonstrating the possible role of this hormone in overweight after menopause. Obesity and overweight correspond to a relevant human health problem that can lead to premature death. Therefore unraveling the mechanisms underlying body mass gain is of great relevance, as well as the development of strategies to prevent its establishment. Energy balance regulation is associated with the control of body mass, and physical exercise is an important modulator of this homeostatic parameter. However, the influence of physical exercise in mass gain development during estrogen deficiency is controversial and depends on the exercise protocol used. In this study, we in...
Arquivos brasileiros de endocrinologia e metabologia, 2004
Thyroid hormone biosynthesis depends on iodide uptake and its incorporation into the acceptor pro... more Thyroid hormone biosynthesis depends on iodide uptake and its incorporation into the acceptor protein thyroglobulin (Tg), a high molecular weight protein secreted into the follicular lumen. The sodium-iodide symporter (NIS) is responsible for thyroid iodide uptake, the first step in thyroid hormonogenesis. Iodide is subsequently transported through the cellular membrane by pendrin (PDS) and then incorporated into Tg. Iodide oxidation and organification occur mainly in the thyrocyte apical surface and these reactions are catalyzed by thyroperoxidase (TPO) in the presence of hydrogen peroxide. Thus, thyroid iodide organification depends on TPO activity, which is modulated by the concentration of substrates (thyroglobulin and iodide) and cofactor (hydrogen peroxide). Hydrogen peroxide generation is catalyzed by the thyroid NADPH oxidase (ThOx), which is present in the apical pole of thyrocytes, is stimulated by thyrotropin and is inhibited by iodide. Hydrogen peroxide generation is the...
To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thic... more To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency (GHD), mean age 42.5 +/- 10.1 years, were studied and compared with 29 control subjects matched for sex, age, body mass index, and smoking habits. Lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein), serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the carotid arteries were performed at baseline and at 6, 12, and 24 months during GH therapy on maintenance dose. At baseline, when compared with the control group, patients presented increased carotid artery IMT (P < .05) and triglyceride levels (P < .001) and lower HDL concentrations (P < .01). In a linear regression analysis, age and known mean duration of GHD were correlated with carotid artery IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery IMT was observed (P < .01). The apolipoprotein B levels decreased significantly after the first 3 months of GH treatment (P < .001) and remained stable thereafter. Women also presented an increase in HDL cholesterol levels (P < .01). No differences were observed in the other lipids measured. Carotid artery IMT at baseline was inversely correlated with the change in carotid artery IMT (Delta = 24 months - baseline), r = 0.63, P < .001. In conclusion, 24 months of GH replacement therapy promoted favorable effects on carotid artery IMT and lipid profile in patients with GHD. Long-term follow-up studies are required to show whether these beneficial effects will result in reduction of morbidity and mortality from vascular disease.
This investigation evaluated and correlated clinical, laboratorial aspects and psychiatric sympto... more This investigation evaluated and correlated clinical, laboratorial aspects and psychiatric symptoms in sub clinical hypothyroidism (SH). Cross sectional study involving 103 patients with SH and 60 subjects without thyroid disease. Clinical and psychiatric evaluation was respectively based on the Zulewski score and Hamilton A, Hamilton D and Beck questionnaires. Serum thyreotropin (TSH), (thyroxine) FT4 and (antithyroperoxidase) ATPO were measured in all participants. Analysis of continuums data was assessed by the Student t- test, for normally distributed data, and by the Mann- Whitney and Kruskal Wallis tests for non-parametric data. The chi2, Fisher's and Kruskal Wallis tests were used to study qualitative variables. Multivariate analyses were used to study confounding variables. Mean serum TSH level was 7.76 +/- 2.9 micro UI/mL in SH and 1.66 +/- 0.6 micro UI/mL in the group without thyroid disease (p=0.001). Mean serum T4L was slightly lower among patients with HS, and showe...
International journal of pediatric endocrinology, 2010
Objectives. To evaluate, in children with Silver-Russell Syndrome, the response to the IGF-I and ... more Objectives. To evaluate, in children with Silver-Russell Syndrome, the response to the IGF-I and IGFBP-3 generation test and compare results to the growth response after 6 months of rhGH. Methods. Eight children (6 males), with a mean age of 5.71 ± 2.48 years and height SDS of -3.88 ± 1.28 received rhGH for 6 months. IGF-I and IGFBP-3 were analyzed before and after 4 doses of rhGH. Results. The mean growth velocity (GV) before treatment was 5.28 ± 1.9 cm/year. GV increased after rhGH in five children to a mean GV of 10.3 ± 3.64 cm/year. Six children had normal basal IGF-I levels and two low levels. After 4 doses of rhGH, the IGF-I levels were normal in seven. There was no correlation between the growth response and the IGF-I generation test. Conclusions. Children with SRS have normal IGF-I generation test. There is no correlation between the generation test and the growth velocity after 6 months of rhGH.
Arquivos Brasileiros De Endocrinologia E Metabologia, 2008
The amplifi cation of thyroglobulin (TG) mRNA in peripheral blood of patients with thyroid cancer... more The amplifi cation of thyroglobulin (TG) mRNA in peripheral blood of patients with thyroid cancer has been studied for almost one decade, but its real con- tribution for diagnosis of cancer relapse has not yet been established. In the present paper we report the case of a patient with papillary thyroid cancer with undetectable stimulated serum thyrogobulin levels after thyroid
European journal of endocrinology / European Federation of Endocrine Societies, 2014
Several studies have suggested an association between subclinical hypothyroidism (SCH) and increa... more Several studies have suggested an association between subclinical hypothyroidism (SCH) and increased cardiovascular risk. The aim of this study was to evaluate the presence of coronary artery disease (CAD) in asymptomatic patients with SCH by measuring the coronary artery calcium score (CACS). A total of 222 asymptomatic subjects (103 SCH and 119 euthyroid (EU)), who were between the ages of 35 and 65 years and had no previous history of CAD, were enrolled for this cross-sectional analysis. The criteria for SCH included a confirmed normal serum free thyroxine and high TSH levels. Lipid profile, Framingham risk score (FRS) and CACS analyses were performed for all subjects. The SCH and EU groups were comparable with respect to age, gender, BMI and frequency of diabetes, systemic arterial hypertension, hypercholesterolaemia and smoking. There was no difference in the median CACS between the SCH and EU groups. However, in the subgroup of subjects with intermediate/high FRS (AR10y ≥10%),...
Insulinomas ocultos são tumores não detectáveis aos exames convencionais. O estímulo superseletiv... more Insulinomas ocultos são tumores não detectáveis aos exames convencionais. O estímulo superseletivo arterial com cálcio e coleta venosa hepática (EACV) é um exame que pode ser utilizado para localizar o segmento pancreático acometido pelo tumor. Relatamos o caso de uma ...
Although well-differentiated thyroid carcinomas are usually curable by the combined effects of su... more Although well-differentiated thyroid carcinomas are usually curable by the combined effects of surgery, radioiodine ablation and thyroid stimulating hormone (TSH) suppressive therapy, recurrence develops in 20-40% of patients. During tumour progression, cellular de-differentiation occurs in up to 30% of cases and is usually accompanied by more aggressive growth, metastasis spread and loss of iodide uptake. The therapeutic options for de-differentiated thyroid cancer are limited and generally not efficient. Retinoic acids (RA) are biologically active metabolites of vitamin A that regulate growth and differentiation of many cell types, by binding to specific nuclear receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Recent studies have shown that RA can induce in vitro re-differentiation of thyroid carcinoma cell lines, as suggested by increased expression of the sodium/iodide symporter (NIS), type I iodothyronine deiodinase, alkaline phosphatase and by the increment of cellular (131)I uptake. In addition to re-differentiating effects, RA also exert anti-proliferative actions, as the inhibition of mitosis and the induction of apoptosis. Previous clinical studies have shown that iodide uptake may be re-stimulated after RA in about 20-50% of patients with radioiodine non-responsive thyroid carcinoma. Longer follow-up of patients demonstrated that, besides iodide uptake increment, RA can induce tumour regression or at least tumour growth stabilisation. The therapy is generally well tolerated and the most frequent side effects are dryness of skin and mucosa, and hypertriglyceridemia. This paper describes the recent advances in the field of thyroid cancer therapy and reviews the use of RA as a promising novel therapeutic tool.
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