Genetic association of the PERIOD3 (PER3) Clock gene with extreme obesity.

BACKGROUND: Obesity has reached epidemic proportions worldwide, affecting life quality and span. Susceptibility to obesity is partly mediated by genetic differences. Indeed, several genes from the clock gene family have already been shown to be intimately associated with obesity in diverse ethnic groups. In the present study, an association between BMI and the rs707467, rs228697 and rs228729 PER3 (Period Circadian Clock 3) polymorphisms in subjects with class II (BMI ≥ 35.0-39.9 kg/m2) and class III obesity (>40 kg/m2, extreme obesity) were carried out using TaqMan real-time PCR. Overall, 259 Brazilian adults were genotyped, of whom 122 had class II or III obesity (BMI ≥ 35.0 kg/m2) and 137 were controls having normal weight (BMI > 18.5 and <24.9 kg/m2). RESULTS: PER3 tag SNP (rs228729) shows a significant association with extreme obesity (1000 permutation p = 0.03 and p = 0.04), for genotype and allele frequency respectively) and a haplotype among the three assessed SNPs (alleles G/T/A, rs228697, rs228729, and rs707467, respectively, 1000 permutation p = 0.03) was significantly more prevalent in the group with obesity. CONCLUSION: This exploratory association study suggests that PER3 rs228729 may be associated with extreme obesity in Brazilian adults, however, replication is needed.

The Effect of a Muscle Weight-Bearing and Aerobic Exercise Program on the Body Composition, Muscular Strength, Biochemical Markers, and Bone Mass of Obese Patients Who Have Undergone Gastric Bypass Surgery.

BACKGROUND: The effect of an exercise program on the body composition, muscular strength (MS), biochemical markers, and bone mineral density (BMD) of individuals undergoing gastric bypass is unclear. We assessed lean mass (LM), MS, bone remodeling markers, and BMD before and after supervised weight-bearing and aerobic exercise training in obese patients who underwent Roux-en-Y gastric bypass (RYGB). METHODS: This study included 37 obese patients (81.1% women, mean age 38.2 years, mean body mass index 42.4 ± 0.5 kg/m2). Whole body densitometry was used to evaluate pre- and postoperative BMD, total body fat, and LM. Serum calcium, parathyroid hormone, 25-hydroxyvitamin D, and bone remodeling markers were measured. MS was determined through the concentric 10 repetition maximum test. Postoperatively, participants were divided into two groups: the training group, who followed an exercise program (TG, n = 18), and the control group, who did not (CG, n = 19). RESULTS: After 1 year, the TG showed a lower decrease in total BMD and at the lumbar spine and right hip compared with the CG (p < 0.001). The TG had lower mass reduction and an increase in upper limb LM compared with the CG (both p < 0.05). There was no significant difference between groups in bone markers or calcium metabolism. MS was higher in the TG than the CG (p < 0.05). CONCLUSION: The supervised exercise program attenuated lumbar spine and right hip BMD loss and improved LM in the arms and overall MS but did not affect bone remodeling.

Ability of body mass index to predict abnormal waist circumference: receiving operating characteristics analysis.

BACKGROUND: Body mass index (BMI) and waist circumference (WC) are the most used anthropometric measures to identify obesity. While BMI is considered to be a simple and accurate estimate of general adiposity, WC is an alternative surrogate measure of visceral obesity. However, WC is subject to significant inter-examiner variation. The aim of the present study was to correlate BMI and WC measures in a group of Brazilian adults to determine the most accurate BMI values for predicting abnormal WC. METHODS: BMI and WC were measured in 1184 volunteers (45.6 ± 17.3 yrs; 69% female) using standard procedures. Abnormal WC was defined as ≥88 cm in women and ≥102 cm in men using the traditional criteria, and ≥80 cm in women and ≥90 cm in men using the new criteria. Statistical analysis involved the calculation of Pearson's correlation coefficients and receiver operating characteristic (ROC) curves. RESULTS: BMI was strongly correlated with WC (women: r = 0.87, p < 0.0001, area under ROC curve = 0.93 ± 0.1; men: r = 0.89, p < 0.0001, area under ROC curve = 0.94 ± 0.01). The most accurate BMI cutoff point for abnormal WC was 27.1 kg/m2 for men and 26.8 kg/m2 for women using the traditional WC criteria, and 24.7 kg/m2 for men and 24.9 kg/m2 for women using the new WC criteria. CONCLUSION: Based on the strong correlation found with WC, BMI can be used as the primary anthropometric measure to estimate adiposity, since both obese and most overweight subjects will have abnormal WC.

Análise de fatores que se associam a alterações no teste de tolerância oral à glicose, independentemente dos valores da glicemia de jejum / Analysis of factors associated with changes in the oral glucose tolerance test, regardless of the values of fasting glucose

OBJETIVO: Identificar fatores associados a alterações do teste oral de tolerância à glicose (TOTG), independentemente da glicemia de jejum (GJ). SUJEITOS E MÉTODOS: 377 pacientes (53,8 ± 15,2 anos; 77,7 por cento mulheres e IMC = 31,4 ± 5,9 kg/m²), sem história de diabetes melito (DM), foram submetidos ao TOTG e comparados de acordo com o resultado: normal (NGT), intolerantes (IGT) e DM. RESULTADOS: 202 pacientes (53,6 por cento) apresentaram TOTG alterado, sendo identificados 69 com DM (18,3 por cento) e 133 com IGT (35,3 por cento). Na análise multivariada, os fatores, além da GJ, que se associaram (P < 0,05) ao TOTG alterado foram: idade (DM = 58,7 ± 12,9; IGT = 56,7 ± 14,3; NGT = 49,6 ± 15,6 anos), hipertensão arterial (DM = 69,6 por cento; IGT = 63,9 por cento; NGT = 43,4 por cento), GJ (DM = 111,9 ± 9,2; IGT = 103,5 ± 10,3; NGT = 96,6 ± 11,1 mg/dL), HbA1C (DM = 6,1 ± 0,7 por cento; IGT = 6,1 ± 0,5 por cento; NGT = 5,8 ± 0,4 por cento), triglicérides (DM = 179,3 ± 169,9; IGT = 154,2 ± 84,1; NGT = 129,1 ± 71,9 mg/dL), HDL-c (DM = 44,7 ± 9,2; IGT = 47,5 ± 12,3; NGT = 50,6 ± 13,4 mg/dL) e ácido úrico em mulheres (DM = 5,3 ± 1,5; IGT = 5,3 ± 1,3; NGT = 4,7 ± 1,3 mg/dL). CONCLUSÃO: Idade, hipertensão arterial, níveis elevados de triglicérides, de HbA1C e de ácido úrico (em mulheres) e baixos níveis de HDL-c se associam a alterações do TOTG em pacientes com sobrepeso/obesidade, independentemente da GJ.

OBJECTIVE: To identify factors associated with changes in oral glucose tolerance test (OGTT), regardless of fasting glucose (FG). SUBJECTS AND METHODS: 377 patients (53.8 ± 15.2 years, 77.7 percent women and BMI = 31.4 ± 5.9 kg/m²) with no history of diabetes mellitus(DM), underwent OGTT and compared according to the results: normal (NGT), impaired (IGT) and DM. RESULTS: 202 patients (53.6 percent) had altered glucose tolerance: 69 with DM (18.3 percent) and 133 with IGT (35.3 percent). In multivariate analysis, factors regardless of FG that were associated (P < 0.05) with changes in the OGTT were age (DM = 58.7 ± 12.9; IGT = 56.7 ± 14.3; NGT = 49.6 ± 15.6 years), hypertension (DM = 69.6 percent; IGT = 63.9 percent; NGT = 43.4 percent), FG (DM = 111.9 ± 9.2; IGT = 103.5 ± 10.3; NGT = 96.6 ± 11.1 mg/dL), HbA1C (DM = 6.1 ± 0.7 percent; IGT = 6.1 ± 0.5 percent; NGT = 5.8 ± 0.4 percent), triglycerides (DM = 179.3 ± 169.9; IGT = 154.2 ± 84.1; NGT = 129.1 ± 71.9 mg/dL), HDL-c (DM =44.7 ± 9.2; IGT = 47.5 ± 12.3; NGT = 50.6 ± 13.4 mg/dL) and uric acid in women (DM = 5.3 ± 1.5; IGT = 5.3 ± 1.3; NGT = 4.7 ± 1.3 mg/dL). CONCLUSION: Age, hypertension, elevated triglycerides, HbA1C, uric acid (in women) and low HDL-C are associated with changes in the OGTT patients with overweight / obesity, irrespective of FG.

[Analysis of factors associated with changes in the oral glucose tolerance test, regardless of the values of fasting glucose]. / Análise de fatores que se associam a alterações no teste de tolerância oral à glicose, independentemente dos valores da glicemia de jejum.

OBJECTIVE: To identify factors associated with changes in oral glucose tolerance test (OGTT), regardless of fasting glucose (FG). SUBJECTS AND METHODS: 377 patients (53.8 ± 15.2 years, 77.7% women and BMI = 31.4 ± 5.9 kg/m²) with no history of diabetes mellitus(DM), underwent OGTT and compared according to the results: normal (NGT), impaired (IGT) and DM. RESULTS: 202 patients (53.6%) had altered glucose tolerance: 69 with DM (18.3%) and 133 with IGT (35.3%). In multivariate analysis, factors regardless of FG that were associated (P < 0.05) with changes in the OGTT were age (DM = 58.7 ± 12.9; IGT = 56.7 ± 14.3; NGT = 49.6 ± 15.6 years), hypertension (DM = 69.6%; IGT = 63.9%; NGT = 43.4%), FG (DM = 111.9 ± 9.2; IGT = 103.5 ± 10.3; NGT = 96.6 ± 11.1 mg/dL), HbA1C (DM = 6.1 ± 0.7%; IGT = 6.1 ± 0.5%; NGT = 5.8 ± 0.4%), triglycerides (DM = 179.3 ± 169.9; IGT = 154.2 ± 84.1; NGT = 129.1 ± 71.9 mg/dL), HDL-c (DM =44.7 ± 9.2; IGT = 47.5 ± 12.3; NGT = 50.6 ± 13.4 mg/dL) and uric acid in women (DM = 5.3 ± 1.5; IGT = 5.3 ± 1.3; NGT = 4.7 ± 1.3 mg/dL). CONCLUSION: Age, hypertension, elevated triglycerides, HbA1C, uric acid (in women) and low HDL-C are associated with changes in the OGTT patients with overweight / obesity, irrespective of FG.

[Benign hepatic cyst mimicking thyroid carcinoma metastasis]. / Cisto hepático benigno simulando metástase de carcinoma diferenciado de tireoide.

INTRODUCTION: The follow-up of differentiated thyroid carcinoma (DTC) for detecting persistent or recurrent disease is based on iodine whole body scan (WBS), the evaluation of the tumor marker thyroglobulin (Tg), the anti-thyroglobulin antibody (anti-Tg) and neck ultrasonography (US). Well known false-positive causes of WBS include inflammatory processes, some non-thyroid tumors, kidney or even sebaceous cysts . METHODS: We reported a case of false-positive WBS, after therapeutic dose of (131I) NaI. RESULTS: We enphasize the importance of recognizing benign liver cysts mimicking DTC metastasis. CONCLUSIONS: False-positive and negative results may occur with WBS and must be recognized to avoid mismanagement.

Cisto hepático benigno simulando metástase de carcinoma diferenciado de tireoide / Benign hepatic cyst mimicking thyroid carcinoma metastasis

INTRODUÇÃO: Pesquisa de corpo inteiro após dose terapêutica de (131I) NaI (PCI) associada à tireoglobulina (Tg) sérica, anticorpo antitireoglobulina (anti-Tg) e ultrassom (US) cervical representam os métodos de referência para detecção de carcinoma diferenciado de tireoide (CDT) residual ou metastático. Algumas causas de PCI falsos-positivas, como processos inflamatórios, alguns tumores não tireoidianos e até mesmo cistos renais e sebáceos, são bem conhecidas. MÉTODOS: Neste trabalho, descreveu-se um caso de cisto hepático benigno simulando metástase de carcinoma de tireoide em PCI após dose terapêutica de (131I) NaI. RESULTADOS: Ressalta-se a importância do reconhecimento dos cistos hepáticos benignos como fator complicador do seguimento dos pacientes com câncer de tireoide. CONCLUSÕES: Para minimizar erros de diagnóstico e, consequentemente, na condução dos casos de CDT, é necessário conhecer as possíveis causas de PCI falsos-negativas e positivas.

INTRODUCTION: The follow-up of differentiated thyroid carcinoma (DTC) for detecting persistent or recurrent disease is based on iodine whole body scan (WBS), the evaluation of the tumor marker thyroglobulin (Tg), the anti-thyroglobulin antibody (anti-Tg) and neck ultrasonography (US). Well known false-positive causes of WBS include inflammatory processes, some non-thyroid tumors, kidney or even sebaceous cysts . METHODS: We reported a case of false-positive WBS, after therapeutic dose of (131I) NaI. RESULTS: We enphasize the importance of recognizing benign liver cysts mimicking DTC metastasis. CONCLUSIONS: False-positive and negative results may occur with WBS and must be recognized to avoid mismanagement.

Turner syndrome: searching for better outcomes.

OBJECTIVES: To assess the results of growth hormone on the growth of girls with Turner Syndrome and identify relevant parameters to improve outcomes. METHODS: Growth velocity and final height were studied in a historical cohort of 41 girls, regularly followed up for hormone distribution at three referral centers. The influence of oxandrolone and of estrogens on the final height was analyzed. The girls (initial chronological age=8.9+/-3.4years; initial bone age=7.0+/-3.1years) used 0.19 mg/kg/week of growth hormone for 4.0 +/- 2.0 years. RESULTS: In the first year, growth velocity increased by 71.5% in 41 girls and 103.4% in those who reached final height (11 girls). The whole group had a gain in the height SDS of 0.8 +/- 0.7 (p<0.01) and for those who reached a final height of 1.0 +/- 0.8 (p<0.01). Final height (143.6 +/-6.3 cm) was 3.9 +/- 5.3 cm higher than the predicted height, and the height gain occurred before estrogen therapy. Oxandrolone had no significant influence on height gain. The significant variables contributing to the final height were the duration of growth hormone used and its use prior to starting estrogens, the initial height SDS, and the growth velocity during the first year of treatment. CONCLUSIONS: We concluded that the use of growth hormone significantly increased the final height, which remained lower than the target. Results point to a need for starting growth hormone use as early as possible and to maximize treatment before estrogen replacement. It has been observed that even moderate doses of growth hormone may significantly increase early growth velocity.

Turner syndrome: searching for better outcomes

OBJECTIVES: To assess the results of growth hormone on the growth of girls with Turner Syndrome and identify relevant parameters to improve outcomes. METHODS: Growth velocity and final height were studied in a historical cohort of 41 girls, regularly followed up for hormone distribution at three referral centers. The influence of oxandrolone and of estrogens on the final height was analyzed. The girls (initial chronological age=8.9±3.4years; initial bone age=7.0±3.1years) used 0.19 mg/kg/week of growth hormone for 4.0 ± 2.0 years. RESULTS: In the first year, growth velocity increased by 71.5 percent in 41 girls and 103.4 percent in those who reached final height (11 girls). The whole group had a gain in the height SDS of 0.8 ± 0.7 (p<0.01) and for those who reached a final height of 1.0 ± 0.8 (p<0.01). Final height (143.6 ±6.3 cm) was 3.9 ± 5.3 cm higher than the predicted height, and the height gain occurred before estrogen therapy. Oxandrolone had no significant influence on height gain. The significant variables contributing to the final height were the duration of growth hormone used and its use prior to starting estrogens, the initial height SDS, and the growth velocity during the first year of treatment. CONCLUSIONS: We concluded that the use of growth hormone significantly increased the final height, which remained lower than the target. Results point to a need for starting growth hormone use as early as possible and to maximize treatment before estrogen replacement. It has been observed that even moderate doses of growth hormone may significantly increase early growth velocity.

[Subclinical Cushing's disease: presentation of three cases and critical review]. / Doença de Cushing subclínica: relato de três casos e revisão da literatura.

Unlike subclinical Cushing's disease, adrenal subclinical Cushing's syndrome is widely recognized. It is defined as an autonomous cortisol hyperproduction of mild intensity not causing specific clinical signs, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. Although Cushing's disease accounts for the majority of hypercortisolism states, subclinical Cushing's disease has been rarely reported. Three cases of subclinical Cushing's disease due to pituitary corticotrophic macroadenomas, confirmed by immunohistochemistry, are presented in order to underscore its recognition by clinical endocrinologists and to emphasize a diagnostic evaluation of hypercortisolism in all cases of pituitary adenomas.

Doença de cushing subclínica: relato de três casos e revisão da literatura / Subclinical cushings disease: presentation of three cases and critical review

Ao contrário da doença de Cushing subclínica, a síndrome de Cushing subclínica de origem adrenal é uma entidade amplamente conhecida. É definida como uma hiperprodução autônoma de cortisol, de leve intensidade, insuficiente para causar sinais clínicos específicos de hipercortisolismo, porém suficiente para levar a alterações bioquímicas detectáveis no eixo hipotálamo-hipófise-adrenal. Apesar de a doença de Cushing representar a grande maioria dos casos de hipercortisolismo, há poucos relatos na literatura sobre doença de Cushing subclínica. Neste trabalho são descritos três casos de doença de Cushing subclínica, causadas por macroadenomas hipofisários corticotróficos, confirmados por estudo imuno-histoquímico, despertando a atenção dos endocrinologistas clínicos para essa entidade e sugerindo que a investigação laboratorial do hipercortisolismo seja incluída em todos os casos de adenomas hipofisários.

Unlike subclinical Cushings disease, adrenal subclinical Cushings syndrome is widely recognized. It is defined as an autonomous cortisol hyperproduction of mild intensity not causing specific clinical signs, but detectable biochemically as derangements of the hypothalamic-pituitary-adrenal axis function. Although Cushings disease accounts for the majority of hypercortisolism states, subclinical Cushings disease has been rarely reported. Three cases of subclinical Cushings disease due to pituitary corticotrophic macroadenomas, confirmed by immunohistochemistry, are presented in order to underscore its recognition by clinical endocrinologists and to emphasize a diagnostic evaluation of hypercortisolism in all cases of pituitary adenomas.