Rui Maciel | Universidade Federal de São Paulo (UNIFESP) (original) (raw)

Papers by Rui Maciel

Research paper thumbnail of Desenvolvimento e Validação de Um Método Imunofluorométrico Para a Pesquisa de Anticorpos Antiperoxidase Tiroidiana no Soro

Arquivos Brasileiros De Endocrinologia E Metabologia, 2002

Research paper thumbnail of Paralisia periódica hipocalêmica tirotóxica, uma urgência endócrina: revisão do quadro clínico e genético de 25 pacientes

Arquivos Brasileiros De Endocrinologia E Metabologia, 2004

Research paper thumbnail of RET Y791F variant does not increase the risk for MTC

Thyroid : official journal of the American Thyroid Association, Jan 7, 2015

Letter to the Editor, no abstract available.

Research paper thumbnail of Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

JAMA Internal Medicine, 2015

Some experts suggest that serum thyrotropin levels in the upper part of the current reference ran... more Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Research paper thumbnail of Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

The Journal of clinical endocrinology and metabolism, Jan 9, 2015

To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Stud... more To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratif...

Research paper thumbnail of The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis

Journal of molecular endocrinology, 2014

Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called... more Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called thyrotoxic periodic paralysis (TPP) and is characterised by transient hypokalaemia and hypophosphataemia under high thyroid hormone levels that is frequently precipitated by carbohydrate load. The sulphonylurea receptor 1 (SUR1 (ABCC8)) is an essential regulatory subunit of the β-cell ATP-sensitive K(+) channel that controls insulin secretion after feeding. Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). We verified that the frequency of the alanine 1369 C-allele was significantly higher i...

Research paper thumbnail of perspectivas Monitorização Contínua de Glicose: Análise Crítica Baseada em Experiência ao Longo de Um Ano

Continuous Glucose Monitoring: A Critical Appraisal After One Year Experience. Conventional asses... more Continuous Glucose Monitoring: A Critical Appraisal After One Year Experience. Conventional assessment of glycemic control in diabetes mellitus (DM) includes blood glucose attention to glycemia and glycated hemoglobin levels. Recently, we introduced the continuous glucose-monitoring test (CGM) (Medtronic Minimed - CGMS® System GoldTM). Here we describe our experience with this methodology over the year 2004. A total of 141 CGM

Research paper thumbnail of Comparação entre duas estratégias para a detecção precoce do hipotiroidismo congênito

Revista Da Associacao Medica Brasileira, 1998

RESUMO -OBJETIVO. Comparar em recém-nascidos (RN) duas estratégias diferentes para o rastreamento... more RESUMO -OBJETIVO. Comparar em recém-nascidos (RN) duas estratégias diferentes para o rastreamento do hipotiroidismo congênito (HC), a dosagem primária de TSH no sangue colhido do cordão umbilical (método 1) e a dosagem primária de T4 no sangue colhido por punção de calcanhar no 2 o dia de internação (método 2).

Research paper thumbnail of Desenvolvimento de um método para a determinação da iodúria e sua aplicação na excreção urinária de iodo em escolares brasileiros

Arquivos Brasileiros De Endocrinologia E Metabologia, 2007

Research paper thumbnail of A iodúria de pacientes portadores de tireopatias autoimunes em Santo andré, SP, é comparável à dos indivíduos normais e estável nos últimos dez anos

Arquivos Brasileiros De Endocrinologia E Metabologia, 2009

Research paper thumbnail of Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

Brazilian Journal of Medical and Biological Research, 2001

Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid... more Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 +/- 0.370 to 2.085 +/- 0.364 pmol I-/microg DNA at 1 ng/ml (P<0.02), to 1.970 +/- 0.302 pmol I-/microg DNA at 10 ng/ml (P<0.003), and to 2.038 +/- 0.389 pmol I-/microg DNA at 100 ng/ml (P<0.02). In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 +/- 0.408 to 7.312 +/- 0.506 pmol I-/microg DNA (P<0.02). A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

Research paper thumbnail of Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility

Endocrine-related cancer, 2015

Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-o... more Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been repo...

Research paper thumbnail of Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors

Thyroid, 2005

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tu... more To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

Research paper thumbnail of Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis

Biology open, 2014

Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia asso... more Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with...

Research paper thumbnail of Novel etiopathophysiological aspects of thyrotoxic periodic paralysis

Nature Reviews Endocrinology, 2011

| Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and... more | Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and is the most common cause of acquired periodic paralysis. Typically, paralytic attacks cease when hyperthyroidism is abolished, and recur if hyperthyroidism returns. TPP is often underdiagnosed, as it has diverse periodicity, duration and intensity. The age at which patients develop TPP closely follows the age at which thyrotoxicosis occurs. All ethnicities can be affected, but TPP is most prevalent in people of Asian and, secondly, Latin American descent. TPP is characterized by hypokalemia, suppressed TSH levels and increased levels of thyroid hormones. Nonselective β adrenergic blockers, such as propranolol, are an efficient adjuvant to antithyroid drugs to prevent paralysis; however, an early and definitive treatment should always be pursued. Evidence indicates that TPP results from the combination of genetic susceptibility, thyrotoxicosis and environmental factors (such as a highcarbohydrate diet). We believe that excess T 3 modifies the insulin sensitivity of skeletal muscle and pancreatic β cells and thus alters potassium homeostasis, but only leads to a depolarization-induced acute loss of muscle excitability in patients with inherited ion channel mutations. An integrated etiopathophysiological model is proposed based on molecular findings and knowledge gained from long-term follow-up of patients with TPP. Maciel, R. M. B. et al. Nat. Rev. Endocrinol. advance online publication 10 May 2011;

Research paper thumbnail of INTERAÇÃO ENTRE EXERCÍCIO FÍSICO E SUPLEMENTAÇÃO DE ÁCIDO ASCÓRBICO SOBRE A HISTAMINA TECIDUAL DO MÚSCULO ESQUELÉTICO E CARDÍACO DE COBAIAS SEDENTÁRIAS E TREINADAS

Research paper thumbnail of Basal serum thyroglobulin measured by a second-generation assay is equivalent to stimulated thyroglobulin in identifying metastases in patients with differentiated thyroid cancer with low or intermediate risk of recurrence

European thyroid journal, 2014

Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of ... more Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of TSH-stimulated thyroglobulin (s-Tg) instead of basal Tg on T4 therapy (b-Tg). However, these guidelines were established using first-generation Tg assays with a functional sensitivity (FS) of 0.5-1.0 ng/ml. Current more sensitive second-generation Tg assays (Tg2G; FS 0.05-0.10 ng/ml) have shown that low-risk DTC patients with undetectable b-Tg rarely have recurrences. This study was undertaken to compare b-Tg using a chemiluminescent Tg2G assay (Tg2GICMA; FS 0.1 ng/ml) with s-Tg in DTC patients with an intermediate risk of recurrence. We evaluated 168 DTC patients with a low (n = 101) and intermediate (n = 67) risk of recurrence treated by total thyroidectomy (147 also treated with radioiodine), with a mean follow-up of 5 years. b-Tg was undetectable with the Tg2GICMA in 142 of 168 patients. s-Tg was <2 ng/ml in 138 of these 142 patients, and only 3 of these 138 (2%) presented metasta...

Research paper thumbnail of Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases

European thyroid journal, 2014

Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has no... more Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD). We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay. The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC cu...

Research paper thumbnail of Injeção percutânea de etanol no tratamento de nódulos tiroidianos sólidos, císticos e autônomos

Arquivos Brasileiros De Endocrinologia E Metabologia, 2003

Research paper thumbnail of Distribution of HOMA-IR in Brazilian subjects with different body mass indexes

Arquivos Brasileiros De Endocrinologia E Metabologia, 2006

Research paper thumbnail of Desenvolvimento e Validação de Um Método Imunofluorométrico Para a Pesquisa de Anticorpos Antiperoxidase Tiroidiana no Soro

Arquivos Brasileiros De Endocrinologia E Metabologia, 2002

Research paper thumbnail of Paralisia periódica hipocalêmica tirotóxica, uma urgência endócrina: revisão do quadro clínico e genético de 25 pacientes

Arquivos Brasileiros De Endocrinologia E Metabologia, 2004

Research paper thumbnail of RET Y791F variant does not increase the risk for MTC

Thyroid : official journal of the American Thyroid Association, Jan 7, 2015

Letter to the Editor, no abstract available.

Research paper thumbnail of Thyroid Function Within the Normal Range and Risk of Coronary Heart Disease

JAMA Internal Medicine, 2015

Some experts suggest that serum thyrotropin levels in the upper part of the current reference ran... more Some experts suggest that serum thyrotropin levels in the upper part of the current reference range should be considered abnormal, an approach that would reclassify many individuals as having mild hypothyroidism. Health hazards associated with such thyrotropin levels are poorly documented, but conflicting evidence suggests that thyrotropin levels in the upper part of the reference range may be associated with an increased risk of coronary heart disease (CHD). To assess the association between differences in thyroid function within the reference range and CHD risk. Individual participant data analysis of 14 cohorts with baseline examinations between July 1972 and April 2002 and with median follow-up ranging from 3.3 to 20.0 years. Participants included 55 412 individuals with serum thyrotropin levels of 0.45 to 4.49 mIU/L and no previously known thyroid or cardiovascular disease at baseline. Thyroid function as expressed by serum thyrotropin levels at baseline. Hazard ratios (HRs) of CHD mortality and CHD events according to thyrotropin levels after adjustment for age, sex, and smoking status. Among 55 412 individuals, 1813 people (3.3%) died of CHD during 643 183 person-years of follow-up. In 10 cohorts with information on both nonfatal and fatal CHD events, 4666 of 48 875 individuals (9.5%) experienced a first-time CHD event during 533 408 person-years of follow-up. For each 1-mIU/L higher thyrotropin level, the HR was 0.97 (95% CI, 0.90-1.04) for CHD mortality and 1.00 (95% CI, 0.97-1.03) for a first-time CHD event. Similarly, in analyses by categories of thyrotropin, the HRs of CHD mortality (0.94 [95% CI, 0.74-1.20]) and CHD events (0.97 [95% CI, 0.83-1.13]) were similar among participants with the highest (3.50-4.49 mIU/L) compared with the lowest (0.45-1.49 mIU/L) thyrotropin levels. Subgroup analyses by sex and age group yielded similar results. Thyrotropin levels within the reference range are not associated with risk of CHD events or CHD mortality. This finding suggests that differences in thyroid function within the population reference range do not influence the risk of CHD. Increased CHD risk does not appear to be a reason for lowering the upper thyrotropin reference limit.

Research paper thumbnail of Subclinical Hypothyroidism and the Risk of Stroke Events and Fatal Stroke: An Individual Participant Data Analysis

The Journal of clinical endocrinology and metabolism, Jan 9, 2015

To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Stud... more To determine the risk of stroke associated with subclinical hypothyroidism. Data Sources and Study Selection Published prospective cohort studies were identified through a systematic search through November 2013 without restrictions in several databases. Unpublished studies were identified through the Thyroid Studies Collaboration. We collected individual participant data (IPD) on thyroid function and stroke outcome. Euthyroidism was defined as thyrotropin (TSH) levels 0.45-4.49 mIU/L, subclinical hypothyroidism as TSH levels 4.5-19.9 mIU/L with normal thyroxin levels. Data Extraction and Synthesis We collected IPD on 47,573 adults (3451 subclinical hypothyroidism) from 17 cohorts, followed-up 1972-2014 (489,192 person-years). Age- and sex-adjusted pooled hazard ratio (HR) for participants with subclinical hypothyroidism compared to euthyroidism was 1.05 (95% CI, 0.91-1.21) for stroke events (combined fatal and non-fatal stroke) and 1.07 (95% CI, 0.80-1.42) for fatal stroke. Stratif...

Research paper thumbnail of The insulin-sensitivity sulphonylurea receptor variant is associated with thyrotoxic paralysis

Journal of molecular endocrinology, 2014

Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called... more Thyrotoxicosis is the most common cause of the acquired flaccid muscle paralysis in adults called thyrotoxic periodic paralysis (TPP) and is characterised by transient hypokalaemia and hypophosphataemia under high thyroid hormone levels that is frequently precipitated by carbohydrate load. The sulphonylurea receptor 1 (SUR1 (ABCC8)) is an essential regulatory subunit of the β-cell ATP-sensitive K(+) channel that controls insulin secretion after feeding. Additionally, the SUR1 Ala1369Ser variant appears to be associated with insulin sensitivity. We examined the ABCC8 gene at the single nucleotide level using PCR-restriction fragment length polymorphism (RFLP) analysis to determine its allelic variant frequency and calculated the frequency of the Ala1369Ser C-allele variant in a cohort of 36 Brazilian TPP patients in comparison with 32 controls presenting with thyrotoxicosis without paralysis (TWP). We verified that the frequency of the alanine 1369 C-allele was significantly higher i...

Research paper thumbnail of perspectivas Monitorização Contínua de Glicose: Análise Crítica Baseada em Experiência ao Longo de Um Ano

Continuous Glucose Monitoring: A Critical Appraisal After One Year Experience. Conventional asses... more Continuous Glucose Monitoring: A Critical Appraisal After One Year Experience. Conventional assessment of glycemic control in diabetes mellitus (DM) includes blood glucose attention to glycemia and glycated hemoglobin levels. Recently, we introduced the continuous glucose-monitoring test (CGM) (Medtronic Minimed - CGMS® System GoldTM). Here we describe our experience with this methodology over the year 2004. A total of 141 CGM

Research paper thumbnail of Comparação entre duas estratégias para a detecção precoce do hipotiroidismo congênito

Revista Da Associacao Medica Brasileira, 1998

RESUMO -OBJETIVO. Comparar em recém-nascidos (RN) duas estratégias diferentes para o rastreamento... more RESUMO -OBJETIVO. Comparar em recém-nascidos (RN) duas estratégias diferentes para o rastreamento do hipotiroidismo congênito (HC), a dosagem primária de TSH no sangue colhido do cordão umbilical (método 1) e a dosagem primária de T4 no sangue colhido por punção de calcanhar no 2 o dia de internação (método 2).

Research paper thumbnail of Desenvolvimento de um método para a determinação da iodúria e sua aplicação na excreção urinária de iodo em escolares brasileiros

Arquivos Brasileiros De Endocrinologia E Metabologia, 2007

Research paper thumbnail of A iodúria de pacientes portadores de tireopatias autoimunes em Santo andré, SP, é comparável à dos indivíduos normais e estável nos últimos dez anos

Arquivos Brasileiros De Endocrinologia E Metabologia, 2009

Research paper thumbnail of Estradiol decreases iodide uptake by rat thyroid follicular FRTL-5 cells

Brazilian Journal of Medical and Biological Research, 2001

Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid... more Estradiol has well-known indirect effects on the thyroid. A direct effect of estradiol on thyroid follicular cells, increasing cell growth and reducing the expression of the sodium-iodide symporter gene, has been recently reported. The aim of the present investigation was to study the effect of estradiol on iodide uptake by thyroid follicular cells, using FRTL-5 cells as a model. Estradiol decreased basal iodide uptake by FRTL-5 cells from control levels of 2.490 +/- 0.370 to 2.085 +/- 0.364 pmol I-/microg DNA at 1 ng/ml (P&lt;0.02), to 1.970 +/- 0.302 pmol I-/microg DNA at 10 ng/ml (P&lt;0.003), and to 2.038 +/- 0.389 pmol I-/microg DNA at 100 ng/ml (P&lt;0.02). In addition, 4 ng/ml estradiol decreased iodide uptake induced by 0.02 mIU/ml thyrotropin from 8.678 +/- 0.408 to 7.312 +/- 0.506 pmol I-/microg DNA (P&lt;0.02). A decrease in iodide uptake by thyroid cells caused by estradiol has not been described previously and may have a role in goiter pathogenesis.

Research paper thumbnail of Comprehensive assessment of the disputed RET Y791F variant shows no association with medullary thyroid carcinoma susceptibility

Endocrine-related cancer, 2015

Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-o... more Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been repo...

Research paper thumbnail of Gene expression profiles reveal that DCN, DIO1, and DIO2 are underexpressed in benign and malignant thyroid tumors

Thyroid, 2005

To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tu... more To investigate the molecular events involved in the pathogenesis and/or progression of thyroid tumors, we compared the gene expression profiles of three thyroid carcinoma cell lines, which represent major tumor subtypes of thyroid cancer and normal thyroid tissue. Using cDNA array methodology, we investigated the expression of 1807 open reading frame expressed sequence tags (ORESTES), selected from head and neck tumor libraries generated through the Brazilian Human Cancer Project-LICR/FAPESP. We found that 505 transcripts were differentially expressed in the thyroid carcinoma cell lines. Using a more stringent criterion, transcripts underexpressed or overexpressed more than fivefold in 1 of 3 or 3 of 3 carcinoma cell lines, a list of 55 ESTs were detected. Five candidate genes were further validated by quantitative polymerase chain reaction (qPCR) in an independent set of 52 thyroid tumors and 22 matched normal thyroid tissues. DCN was found underexpressed in a high percentage of the follicular thyroid adenomas, follicular thyroid carcinomas, and follicular variant of papillary thyroid carcinomas. DIO1 and DIO2 were underexpressed in nearly all papillary thyroid carcinomas. These genes not only could help to better define a tumor signature for thyroid tumors, but may, in part, also become useful as potential targets for thyroid tumor treatment.

Research paper thumbnail of Molecular cloning of ion channels in Felis catus that are related to periodic paralyses in man: a contribution to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis

Biology open, 2014

Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia asso... more Neck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with...

Research paper thumbnail of Novel etiopathophysiological aspects of thyrotoxic periodic paralysis

Nature Reviews Endocrinology, 2011

| Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and... more | Thyrotoxicosis can lead to thyrotoxic periodic paralysis (TPP), an endocrine channelopathy, and is the most common cause of acquired periodic paralysis. Typically, paralytic attacks cease when hyperthyroidism is abolished, and recur if hyperthyroidism returns. TPP is often underdiagnosed, as it has diverse periodicity, duration and intensity. The age at which patients develop TPP closely follows the age at which thyrotoxicosis occurs. All ethnicities can be affected, but TPP is most prevalent in people of Asian and, secondly, Latin American descent. TPP is characterized by hypokalemia, suppressed TSH levels and increased levels of thyroid hormones. Nonselective β adrenergic blockers, such as propranolol, are an efficient adjuvant to antithyroid drugs to prevent paralysis; however, an early and definitive treatment should always be pursued. Evidence indicates that TPP results from the combination of genetic susceptibility, thyrotoxicosis and environmental factors (such as a highcarbohydrate diet). We believe that excess T 3 modifies the insulin sensitivity of skeletal muscle and pancreatic β cells and thus alters potassium homeostasis, but only leads to a depolarization-induced acute loss of muscle excitability in patients with inherited ion channel mutations. An integrated etiopathophysiological model is proposed based on molecular findings and knowledge gained from long-term follow-up of patients with TPP. Maciel, R. M. B. et al. Nat. Rev. Endocrinol. advance online publication 10 May 2011;

Research paper thumbnail of INTERAÇÃO ENTRE EXERCÍCIO FÍSICO E SUPLEMENTAÇÃO DE ÁCIDO ASCÓRBICO SOBRE A HISTAMINA TECIDUAL DO MÚSCULO ESQUELÉTICO E CARDÍACO DE COBAIAS SEDENTÁRIAS E TREINADAS

Research paper thumbnail of Basal serum thyroglobulin measured by a second-generation assay is equivalent to stimulated thyroglobulin in identifying metastases in patients with differentiated thyroid cancer with low or intermediate risk of recurrence

European thyroid journal, 2014

Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of ... more Guidelines for the follow-up of differentiated thyroid cancer (DTC) recommend the measurement of TSH-stimulated thyroglobulin (s-Tg) instead of basal Tg on T4 therapy (b-Tg). However, these guidelines were established using first-generation Tg assays with a functional sensitivity (FS) of 0.5-1.0 ng/ml. Current more sensitive second-generation Tg assays (Tg2G; FS 0.05-0.10 ng/ml) have shown that low-risk DTC patients with undetectable b-Tg rarely have recurrences. This study was undertaken to compare b-Tg using a chemiluminescent Tg2G assay (Tg2GICMA; FS 0.1 ng/ml) with s-Tg in DTC patients with an intermediate risk of recurrence. We evaluated 168 DTC patients with a low (n = 101) and intermediate (n = 67) risk of recurrence treated by total thyroidectomy (147 also treated with radioiodine), with a mean follow-up of 5 years. b-Tg was undetectable with the Tg2GICMA in 142 of 168 patients. s-Tg was <2 ng/ml in 138 of these 142 patients, and only 3 of these 138 (2%) presented metasta...

Research paper thumbnail of Development and application of a novel sensitive immunometric assay for calcitonin in a large cohort of patients with medullary and differentiated thyroid cancer, thyroid nodules, and autoimmune thyroid diseases

European thyroid journal, 2014

Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has no... more Serum calcitonin (sCT) is a useful biomarker for medullary thyroid cancer (MTC). Consensus has not been reached concerning sCT measurements in the evaluation of nodular thyroid disease (NTD). We developed a new immunofluorometric assay for sCT and have validated it in samples from 794 patients [203 with MTC, 205 with autoimmune thyroid disease (ATD), 248 with NTD, 80 with differentiated thyroid cancer (DTC) 'free of disease', 58 with chronic renal failure (CRF)] and 178 normal individuals, including samples after pentagastrin tests and samples from the washout of 92 FNA procedures in patients with NTD or MTC. We also compared some samples from patients with low or high calcitonin levels using both this assay and the Nichols Institute Diagnostics (NID) assay. The assay's analytical sensitivity was 1.0 pg/ml. Considering MTC patients prior to surgery, the cut-off values for the 95% reference range were 11.1 pg/ml for males and 5.5 pg/ml for females and employing the ROC cu...

Research paper thumbnail of Injeção percutânea de etanol no tratamento de nódulos tiroidianos sólidos, císticos e autônomos

Arquivos Brasileiros De Endocrinologia E Metabologia, 2003

Research paper thumbnail of Distribution of HOMA-IR in Brazilian subjects with different body mass indexes

Arquivos Brasileiros De Endocrinologia E Metabologia, 2006