Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione

Rio de Janeiro, Brazil

Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione

Rio de Janeiro, Brazil
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Vargens D.D.,Instituto Nacional Of Cgncer | Neves R.R.S.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione | Bulzico D.A.,Instituto Nacional Of Cgncer | Ojopi E.B.,University of Sao Paulo | And 6 more authors.
Pharmacogenetics and Genomics | Year: 2011

There is a considerable interindividual variation in L-thyroxine [3,5,3',5'-tetraiodo-l-thyronine (T 4)] dose required for thyrotropin (thyroid-stimulating hormone) suppression in patients with differentiated thyroid cancer. To investigate whether uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1)-mediated T 4 glucuronidation in liver affects T 4 dose, we genotyped 101 patients for the common UGT1A1-53(TA)n polymorphism and compared T 4 doses among patients having zero (5/6 and 6/6 genotypes), one (6/7 genotype), or two (7/7 and 7/8 genotypes) copies of the low-expression (TA) 7 and (TA)8 alleles. A significant trend for decreasing T 4 dose with increasing number of copies of (TA) 7 and (TA)8 (P=0.037) and significant difference in T 4 dose across the UGT1A1-53(TA)n genotypes (P=0.048) were observed, despite considerable overlap of T 4 doses among different genotypes. These results are consistent with reduced T 4 glucuronidation in patients with low-expression (TA)7 and (TA)8 alleles and provide the first evidence for association between UGT1A1-53(TA)n and T 4-dose requirement for thyroid-stimulating hormone suppression in a natural clinical setting. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Lins A.P.M.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione | Sichieri R.,State University of Rio de Janeiro | Coutinho W.F.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione Iede | Ramos E.G.,Instituto Fernandes Figueira | And 2 more authors.
Ciencia e Saude Coletiva | Year: 2013

The scope of this study was to analyze the factors associated with the prevalence of being overweight and obesity in a population of lowincome adult women living in a metropolitan region and its association with socioeconomic, demographic, reproductive and lifestyle variables, highlighting the importance of healthy eating. A population-based, cross-sectional study was conducted with a random sample of 758 women aged 20 or older living in Campos Elíseos - Duque de Caxias - State of Rio de Janeiro. Bivariate and multivariate hierarchical regression was used to identify factors associated with overweight and obesity. A prevalence of 23% of obesity was found, and a prevalence of 56% of being overweight and obesity combined. An inverse association was found between years of study, being overweight and obesity. Most of the women reported having a healthy diet (73.6%) that increased positively with income, education and age. Failure to consume vegetables weekly was associated with being overweight and not having a healthy diet was associated with obesity. The results of this study demonstrate that even in low-income populations, a higher level of education has an impact on prevention of this problem and in food choices.


Santoro A.B.,Instituto Nacional Of Cancer | Vargens D.D.,Instituto Nacional Of Cancer | De Camargo Barros Filho M.,Camargo Cancer Center | Bulzico D.A.,Instituto Nacional Of Cancer | And 7 more authors.
British Journal of Clinical Pharmacology | Year: 2014

Aim To evaluate the impact of genetic polymorphisms in uridine 5′-glucuronosylytansferases UGT1A1 and UGT1A3 and iodothyronine-deiodinases types 1 and 2 on levothyroxine (T4; 3,5,3′,5′-triiodo-L-thyronine) dose requirement for suppression of thyrotropin (TSH) secretion in patients with differentiated thyroid cancer (DTC).Methods Patients (n = 268) submitted to total thyroidectomy and ablation by 131I, under T4 therapy for at least 6 months were recruited in three public institutions in Brazil. Multivariate regression modelling was applied to assess the association of T4 dosing with polymorphisms in UGT1A1 (rs8175347), UGT1A3 (rs3806596 and rs1983023), DIO1 (rs11206244 and rs2235544) and DIO2 (rs225014 and rs12885300), demographic and clinical variables.Results A regression model including UGT1A haplotypes, age, gender, body weight and serum TSH concentration accounted for 39% of the inter-individual variation in the T4 dosage. The association of T4 dose with UGT1A haplotype is attributed to reduced UGT1A1 expression and T4 glucuronidation in liver of carriers of low expression UGT1A1 rs8175347 alleles. The DIO1 and DIO2 genotypes had no influence of T4 dosage.Conclusion UGT1A haplotypes associate with T4 dosage in DTC patients, but the effect accounts for only 2% of the total variability and recommendation of pre-emptive UGT1A genotyping is not warranted.


Dos Santos Silva C.M.,Federal University of Rio de Janeiro | Barbosa F.R.P.,Federal University of Rio de Janeiro | Barbosa F.R.P.,Rio de Janeiro State Federal University | Lima G.A.B.,Federal University of Rio de Janeiro | And 6 more authors.
Obesity | Year: 2011

Hyperprolactinemia might be related to weight gain, metabolic syndrome (MS), and insulin resistance (IR). Treatment with dopamine agonist (DA) has been shown to reduce body weight and improve metabolic parameters. The objectives of this study were to determine the prevalence of obesity, overweight, MS, and IR in patients with prolactinoma before and after therapy with DA and to evaluate the relation between prolactin (PRL), body weight, fat distribution, leptin levels, IR, and lipid profile before treatment. In addition, we investigated the correlation of the reduction in PRL levels with weight loss and metabolic profile improvement. Twenty-two patients with prolactinoma completed 6 months of treatment with DA. These patients were submitted to clinical (BMI, waist circumference, blood pressure (BP)), laboratory evaluation (leptin, glucose, low-density lipoprotein (LDL)-cholesterol, and triglyceride (TG) levels) and abdominal computed tomography (CT) before and after treatment. The statistical analyses were done by nonparametric tests. At the beginning of the study, the prevalence of obesity, overweight, MS, and IR was 45, 27, 27, and 18%, respectively. After 6 months of treatment with DA, PRL levels normalized, but no significant difference in BMI was observed. However, there was a significant decrease on homeostasis model assessment of insulin resistance (HOMA IR) index, glucose, LDL-cholesterol, and TG levels. This study suggests a possible involvement of prolactinoma on the prevalence of obesity. We should consider that DA may be effective on improving metabolic parameters, and we speculate that a period longer than 6 months of treatment is necessary to conclude whether this drug can interfere in the body weight of patients with prolactinoma. © 2010 The Obesity Society.


De Pinho L.K.J.,Hospital Universitario Clementino Fraga Filho | De Pinho L.K.J.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione | Neto L.V.,Hospital Universitario Clementino Fraga Filho | Neto L.V.,Hospital da Lagoa | And 7 more authors.
Neuroendocrinology | Year: 2011

Background: Some pituitary adenomas exhibit fast growth and invade surrounding structures. To date, there is no robust marker to predict invasiveness. Aim: To evaluate Ki-67, p53 and aryl hydrocarbon receptor-interacting protein (AIP) expression and compare these between invasive and noninvasive somatotropinomas and nonfunctioning pituitary adenomas (NFPAs). Methods: Protein expression was determined by immunohistochemistry. Tumors were classified according to percentage of immunolabeled nuclei for Ki-67 and p53. AIP immunopositivity was graded according to a score encompassing pattern and intensity. Invasiveness was defined according to radiological and surgical criteria. Results: Thirty-eight sporadic somatotropinomas were studied. Median Ki-67 labeling index in invasive and noninvasive tumors was 1.6 (range 0-20.6) and 0.26 (0-2.2), respectively (p = 0.01). With a 2.3% cut-off point obtained by ROC curve analysis, invasive adenomas were distinguished with 100% specificity, 39% sensitivity, and 63% accuracy. Low AIP expression was also correlated with tumor invasiveness (p = 0.001), with sensitivity, specificity and accuracy of 78, 80, and 79%, respectively. Expression of p53 was not different among tumors. Twenty-nine NFPAs were studied, with no significant difference between Ki-67, p53 and AIP expression in invasive and noninvasive tumors. High AIP expression was more frequent in NFPAs, with Ki-67 >3% (p = 0.051), especially when only gonadotrope cell adenomas (n = 25) were considered (p = 0.012). Conclusions: These data suggest, for the first time, that AIP is a better marker of invasiveness in somatotropinomas than Ki-67 and p53. In addition, low AIP expression is observed in invasive somatotropinomas, in contrast with high AIP expression in NFPAs (mainly gonadotrope cell tumors) with high proliferative indices. Copyright © 2010 S. Karger AG, Basel.


Kasuki L.,Hospital Universitario Clementino Fraga Filho | Kasuki L.,Hospital Federal Of Bonsucesso | Neto L.V.,Hospital Universitario Clementino Fraga Filho | Neto L.V.,Hospital Federal da Lagoa | And 3 more authors.
Endocrine Journal | Year: 2012

Pregnancy in acromegalic patients is a rare event, but is usually uneventful, with stable GH and insulin-like growth factor I (IGF-I) levels and no tumor enlargement. Medical treatment can usually be withdrawn without problems and although no major adverse event has been reported, the suspension of drug treatments is generally recommended. No case report exists in the literature regarding evolution of a somatotropinoma with invasiveness markers throughout pregnancy. We report a case of an acromegalic patient who was submitted to surgery and treated with octreotide LAR maintaining a stable residual tumor and an IGF-I close to the normal levels. Her tumor presented with a high Ki-67 (11.6%) and a low aryl hydrocarbon receptor-interacting protein (AIP) expression. When she became pregnant, octreotide LAR was withdrawn, and despite remaining asymptomatic during pregnancy, tumor growth occurred with compression of surrounding structures. In conclusion, pregnancy in acromegalic patients has usually a favorable prognosis with no tumor growth. However, in the presence of high Ki-67 labeling index and low AIP expression, tumor enlargement may occur and somatostatin analogue treatment throughout the pregnancy should be considered. © The Japan Endocrine Society.


Gadelha M.R.,Federal University of Rio de Janeiro | Gadelha M.R.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione | Gadelha M.R.,Hospital Universitario Clementino Fraga Filho | Frohman L.A.,University of Illinois at Chicago
Frontiers of Hormone Research | Year: 2010

Familial acromegaly may occur as a component of syndromes of multiple endocrine neoplasia or as isolated familial somatotropinoma (IFS), which is included in the spectrum of familial isolated pituitary adenoma (FIPA). We review the pathogenesis of IFS, from the detection of loss of heterozygosity at chromosome 11q13 and establishment of linkage to this chromosome region to the description of germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene. Approximately 40% of IFS families harbor an AIP mutation. In addition, we summarize the clinical features of IFS families with AIP mutations: The adenomas are diagnosed at a young age and are larger than in IFS patients without AIP mutations or in sporadic somatotropinomas, indicating more aggressive disease. Copyright © 2010 S. Karger AG, Basel.


Casini A.F.,Federal University of Rio de Janeiro | Neto L.V.,Federal University of Rio de Janeiro | Neto L.V.,Hospital da Lagoa | Fontes R.,Diagnosticos da America | And 4 more authors.
Clinical Endocrinology | Year: 2011

Background Acromegaly is associated with increased cardiovascular mortality, and increased aortic root diameter has been recently described in the literature as a possible feature of acromegalic cardiomyopathy. Objective To assess the aortic root diameter and the prevalence of aortic ectasia in acromegalic patients. Patients and methods This paper presents a transversal analysis of 42 acromegalic patients by Doppler echocardiogram and comparison with 42 age, sex, body surface area and hypertension matched controls. Results The mean aortic root diameter at the level of the aortic leaflets was increased in acromegalic patients when compared to controls (3 ·4 ± 0 ·5 vs 2 ·9 ± 0 ·4 cm, respectively, P < 0 ·0001). The aortic root diameter was significantly greater in men than in women (3 ·6 ± 0 ·6 cm vs 3 ·2 ± 0 ·4 cm, respectively, P = 0 ·004), and the left ventricular mass index was positively correlated with the diameter of the aorta (r = 0 ·37, P = 0 ·01). Using a cut-off point ≥yen; 3 ·8 cm, an aortic ectasia prevalence of 26 ·1 vs 2 ·3% was found in acromegalic patients and controls, respectively (P = 0 ·002). Only acromegaly was associated with aortic ectasia (P = 0 ·01). Conclusion The aortic root diameter was higher, and the prevalence of aortic ectasia was more common in acromegalic patients than in controls. In addition, only acromegalic disease was associated with aortic ectasia, suggesting the direct effects of GH and insulin-like growth factor-I excess on the cardiovascular system. © 2011 Blackwell Publishing Ltd.


PubMed | Lund University, Federal University of Rio de Janeiro and Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione
Type: Journal Article | Journal: Arquivos brasileiros de endocrinologia e metabologia | Year: 2014

Zinc transporter 8 autoantibodies (ZnT8A) have been poorly studied in non-Caucasian individuals. We aimed to investigate the prevalence of ZnT8 autoantibodies in patients with T1D and their first degree relatives (FDR) from a multiethnic population, as well as its relation with the insulin (INS) or the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene polymorphisms.ZnT8A were analyzed in sera from T1D patients (n = 72, mean age of 30.3 11.4 years) of variable duration (15.7 11.8 years) and their FDR (n = 78, mean age of 18.3 9.1 years) by a triple mix Radioligand Binding Assay (RBA) for the ZnT8 autoantibody (ZnT8-RWQ) variants. SNP (single nucleotide polymorphism) for INS and PTPN22 were genotyped.The prevalence of ZnT8A was higher in T1D patients than FDR, for ZnT8TripleA (24% vs. 4%,p = 0.001), ZnT8RA (24% vs. 4%, p < 0.001) and ZnT8QA (15% vs. 3%, p = 0.004). All FDR with ZnT8A (n = 3) had at least another positive antibody. Heterozygosis for PTPN22 was associated with a higher frequency of ZnT8TripleA (p = 0.039) and ZnT8RA (p = 0.038).ZnT8A is observed in non-Caucasian patients with T1D, even years after the disease onset, as well as in their FDR. In those, there was an overlap between ZnT8A and other T1D antibodies. ZnT8A was associated with PTPN22 polymorphisms. Further longitudinal studies are necessary to elucidate the importance of these findings in the natural history of T1D patients with multiethnic background.


Collett-Solberg P.F.,Instituto Estadual Of Diabetes E Endocrinologia Luiz Capriglione
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Although recombinant human GH(rhGH) has been available since 1985, there are several questions related to its use that remain unanswered. The Entrez-PubMed search engine was used to conduct a review of publications appearing since 2007 that address growth and GH treatment. Recent publications related to the diagnosis of GH deficiency, genetics of growth, the use of rhGH in different genetic conditions, in idiopathic short stature, and in puberty, and strategies to adjust rhGH dose were reviewed. New studies investigating the genetics of growth and the response to rhGH therapy in different groups are helping in the understanding of the physiology of normal growth. Although in most children treated with rhGH there is a short-term benefit, the clinical relevance of the benefits after long-term treatment in some conditions remains unclear. The challenges are to define milder forms of GH deficiency and to assess the relevance of the benefits, if any, caused by rhGH in different patient populations and the best therapeutic approach for these patients. Well-designed long-term studies using anthropometric, genetic,andlaboratory data that will also assess long-term quality of life benefits are needed to help clinicians select patients to initiate treatment with rhGH and to adjust treatment to improve outcome. Copyright © 2011 by The Endocrine Society.

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