Resumo em Inglês:

Objective Lymph node metastases (LNM) are frequent in patients with papillary thyroid cancer (PTC). The risk of persistent disease (PD) and tumor recurrence (TR) is increased when factors for poor prognosis other than LNM exist, when LNM are numerous, large, detected by preoperative ultrasonography (US), or exhibit extranodal extension. This study evaluated the risk of PD and TR in patients with LNM not exhibiting these characteristics. Subjects and methods Eighty-six patients with 5 or fewer LNM detected during intraoperative inspection, but not by preoperative US, who had no other factors for poor prognosis [tumors > 4 cm, extensive extrathyroid invasion, vascular invasion, aggressive histological subtype, distant metastases, incomplete tumor resection], were studied. All patients underwent total thyroidectomy followed by radioiodine ablation. PD was defined as metastases on initial post-therapy whole-body scans (RxWBS) or detected by imaging methods up to 12 months after ablation. TR was defined as structural disease diagnosed more than one year after ablation in patients without PD. Results PD was diagnosed in 3/86 patients (3.5%). TR was observed in 2/83 patients (2.5%) after 62 months of follow-up. There was no case of death due to the disease. A correlation was observed between pre-ablation Tg and PD or TR [1/48 (2%) with Tg ≤ 2 ng/mL versus 2/22 (9%) with Tg > 2 ≤ 10 ng/mL versus 2/7 (28.5%) with Tg ≥ 10 ng/ml)]. It is noteworthy that 38 patients had up to 3 positive LN and pre-ablation Tg ≤ 2 ng/ml, and none of them had PD or TR. Conclusions The frequency of PD and TR was low in patients with PTC with 5 or fewer LNM and without other factors for poor prognosis. Low postoperative stimulated Tg was predictive of the absence of PD and TR in these patients.

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Objective The purpose of the present study was to investigate the correlation between serum testosterone levels and bone mineral density (BMD) in postmenopausal women. Materials and methods The study group was made up of postmenopausal women admitted to our tertiary center. Serum calcium, phosphorus, albumin, parathyroid hormone (PTH), thyrotropin (TSH), 25-OH vitamin D, and total testosterone concentrations were measured. Subjects were categorized into three groups regarding bone mineral density (BMD) values: normal (n = 22), osteopenia (n = 21), and osteoporosis (n = 21). Subjects were also categorized into three groups according to serum testosterone levels: low testosterone (n = 10), normal testosterone (n = 42), and high testosterone (n = 12). Results No significant difference was found for serum testosterone, TSH, calcium, phosphorus, albumin, PTH, and 25-hydroxyvitamin D levels among patients with normal BMD, osteopenia, and osteoporosis (p > 0.05). Lumbar spine, total femur, femoral neck, trochanteric, intertrochanteric, and Ward’s triangle BMD values were similar for the different testosterone levels (p > 0.05). Conclusion There was no correlation between serum testosterone levels and patient age, body-mass index, or any measured BMD values. Given the findings in our study, which failed to demonstrate a statistically significant relationship between testosterone and BMD, adjustment of other risk factors for osteoporosis might have a more distinctive effect in this setting.

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Objective This study aimed to get the genotypic and allelic frequencies of rs1801282 in 179 volunteer donors and 154 patients with Metabolic syndrome (MetS) in Brasilia, Brazil and also examine the association with anthropometric, biochemical and hemodynamic variables in the latter group. MetS comprises a group of diseases resulting from insulin resistance, in-creased risk of type 2 diabetes and atherosclerotic cardiovascular disease. MetS is defined by the presence of increased visceral fat, atherogenic dyslipidemia (elevated triglycerides (TGL)), with decreased high density lipoprotein (HDL) and increased low density lipoprotein (LDL) levels, hypertension (BPH) and disturbances in glucose homeostasis representing a significant burden across the world due to the alarming increase in the incidence over the last decades besides their significant morbidity and mortality. Peroxisome proliferator activated receptor-gamma (PPARg) has been mentioned as a candidate gene for determining the risk of MetS. It is a member of the nuclear receptors superfamily and a ligand-activated transcription factor, which regulates the expression of genes involved in the network lipogenesis and adipogenesis, insulin sensitivity, energy balance, inflammation, angiogenesis and atherosclerosis. Among the PPARG genetic variants, single nucleotide polymorphism rs1801282 has been the most extensively studied one since it was first described by Yen and cols. in 1997. This polymorphism is characterized by the replacement of a proline (CCC) to an alanine (GCA) at codon 12 of exon B, due to the exchange of a cytosine with a guanine. The Ala allele frequency varies in different ethnic groups. Materials and methods DNA was extracted using Chelex-100 method and determinations of genotypes were performed by allele-specific chain reaction. Results The distribution of genotype frequency of the MetS group was not statistically different from the frequency in the donor population at large. In the first group, genotype frequency was CC to 0.869 and 0.103 for CG, while allelic frequencies were 0.948 for C and 0.052 for G allele. In the group of donors, the genotype and allele frequencies were 0.882 for CC, 0.117 to CG; and 0.941 to 0.059 for G and C, respectively. GG genotype was not found in any of the two groups. The genotype distribution and allele frequencies were in Hardy-Weinberg equilibrium. No marker could be detected from the analysis of anthropometric, biochemical and hemodynamic variables in the MetS group. Conclusion Our data suggest that this polymorphism is not correlated with predisposition to MetS. The results obtained on a small sample of the population of Brasilia, corroborate the data reported in the literature on the prevalence of this polymorphism in PPAR in populations of different ethnic origins.

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Objective The purpose of the present study was to analyze the effects of a 20-week concurrent training (20 WCT) intervention program on gender-specific body composition and metabolic variables in obese adolescents. Subjects and methods Sample was composed of twenty-five obese adolescents, aged between 12 and 15 (13.4 ± 0.96) years. Fat-free mass (FFM), percentage trunk fat mass (TFM%) and percentage fat mass (%FM) were evaluated through dual-energy X-ray absorptiometry (DXA). Measurement of intra-abdominal adiposity (IAAT) was performed using ultrasound. Blood pressure was measured and blood samples analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides (TG) and plasma glucose. All participants performed the concurrent training (combination of weight training and aerobic training) three times per week, one hour per day, for 20 weeks. Descriptive analysis and analysis of variance (ANOVA) for repeated measures were used to compare baseline, 10 week and 20 week moments using the Bonferroni post-hoc test. Statistical significance was set at p < 0.05. Significant decrease in TC, LDL-c and TFM% were verified in both genders after the 10 initial weeks of concurrent training. Results A significant increase in height was found in both the male and female groups (p = 0.001 and p = 0.047, respectively), after 20 weeks of concurrent training. In addition, several modifications were observed in body composition and metabolic variables, with a significant decrease in BMI (p = 0.002 and p = 0.017), BMI z-score (p = 0.033 and p = 0.004), FM% (p = 0.002 and p = 0.002), TFM% (p = 0.009 and p = 0.018), TC (p = 0.042 and p = 0.001) and LDL-c (p = 0.006 and p = 0.001) in the male and female groups, respectively, after 20 weeks of intervention when compared with baseline. Conclusion Our results identified that concurrent training was an effective intervention for treating metabolic variable and body composition disorders, in both genders, by decreasing adiposity with consequent improvement in BMI and BMI z-scores, and enhancement in lipid profile variables.

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Objective To evaluate circulating E-selectin levels in patients with nonfunctional adrenal incidentaloma (NFA) in relation to insulin resistance and early atherosclerosis. Subjects and methods A total of 40 patients with NFA (mean [SD] age: 55.6 [10.7] years; 70% were females) and 35 controls (mean [SD] age: 51.5 [8.1] years; 71.4% were females) selected from age-, gender- and body mass index (BMI)- matched healthy subjects were enrolled. Serum hsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated. High-resolution B-mode ultrasonography was performed. Serum levels of E-selectin were evaluated by enzyme-linked immunosorbent assay. Results Patients with NFA had significantly higher values for E-selectin (14.9 (4.8) vs. 12.2 (4.1) ng/mL, p < 0.01) and CIMT (0.6 (0.1) vs. 0.5 (0.1) mm, p < 0.05) than controls. Serum E-selectin levels showed a statistically significant association with hsCRP (r = 0.751, p < 0.001), HOMA-IR (r = 0.575, p < 0.001) and CIMT (r = 0.762, p < 0.001). CIMT (Carotid intima media thickness) was increased in patients with NFA patients with NFA were more insulin resistant than controls and statistically significant relationship was found between size of tumor and HOMA-IR (r = 0.361, p < 0.001). Conclusion In conclusion, based on significantly higher values for E-selectin, CIMT and HOMA-IR in patients with NFA than controls along with significant correlation of E-selectin levels to CIMT, HOMA-IR and hs-CRP, our findings seems to indicate an increased risk of early atherosclerosis and impaired endothelial function in NFA patients, particularly in case of insulin resistance.

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Objective Oxidative damage may be responsible for the pathogenesis and complications of many diseases. Vitamin D deficiency has been suggested as a potential mediator of various extra-skeletal pathologies. However, there are limited data on anti-oxidant properties of vitamin D. Materials and methods Forty-one subjects with vitamin D deficiency and 30 healthy controls were enrolled into the study. The levels of total anti-oxidant status (TAS), total oxidant status (TOS), ischemia-modified albumin (IMA), oxidized-low density lipoprotein (ox-LDL), high-sensitivity C-reactive protein (hs-CRP) and fibrinogen were measured in both groups. The measurements were repeated in 17 patients after the replacement of vitamin D. Results Serum IMA and TOS levels were significantly higher (p < 0.001 and p = 0.035, respectively), while TAS levels were significantly lower in patients, compared to controls (p < 0.001). Additionally, fibrinogen was significantly higher in patients than controls (p = 0.003), while ox-LDL and hs-CRP levels were similar between two groups. After the replacement of vitamin D, TAS level significantly increased (p = 0.037), and TOS and fibrinogen levels significantly decreased (p = 0.043 and p = 0.010, respectively). Vitamin D levels were negatively correlated with IMA and fibrinogen levels (r = -0.500, p < 0.001 and r = -0.391, p = 0.002, respectively), although positively correlated with TAS levels (r = 0.430, p < 0.001). No correlation was found between vitamin D levels, and the TOS, ox-LDL and hs-CRP levels. Conclusions In this study, while serum IMA, TOS and fibrinogen levels were increased, TAS levels were seen to be decreased in patients with vitamin D deficiency. These results suggest that oxidative/anti-oxidative balance shifts in favours of oxidative status in vitamin D deficiency.

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Objective The aim of this study was to investigate the association between total and abdominal adiposity with metabolic parameters and inflammatory markers, in female adolescents. Subjects and methods The sample consisted of 53 adolescents aged 13 to 17 years from a public school in Curitiba, Brazil. The adiposity indicators studied were body mass index (BMI), waist circumference (WC), trunk fat mass (TKFM), total fat mass (TFM) and body fat percentage (BF%) measured by dual-energy X-ray absorptiometry. The metabolic and inflammatory parameters studied were systolic blood pressure (SBP), diastolic blood pressure (DBP), glucose, insulin, homeostasis model assessment index for insulin resistance (HOMA-IR), lipids, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), leptin, adiponectin and resistin. Results Eighty percent of WC variation, 87% of TKFM and TFM, and 73% of BF% were predicted by BMI variation. There was a significant positive correlation between all indicators of adiposity with SBP, DBP, insulin, HOMA-IR, CRP and leptin. Triglycerides were positively correlated with BMI and WC, and adiponectin correlated negatively with BMI. TNF-α, IL-6, glucose, total cholesterol, and high- and low-density lipoprotein cholesterol did not correlate to the studied variables. Conclusion BMI showed a significant association with most of the parameters studied, and WC was slightly better than BMI to predict insulin resistance in this specific population.

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Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

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Medullary thyroid carcinoma (MTC) may rarely present with paraneoplastic syndromes. Among the most frequent ones are the appearance of diarrhea and ectopic Cushing syndrome (ECS). The ECS in the context of MTC is usually present in patients with distant metastatic disease. The use of drugs such as ketoconazole, metyrapone, somatostatin analogs and etomidate have been ineffective alternatives to control hypercortisolism in these patients. Bilateral adrenalectomy is often required to manage this situation. Recently, the use of tyrosine kinase inhibitors has been shown to be a useful tool to achieve eucortisolism in patients with metastatic MTC and ECS. We present a patient with sporadic advanced persistent and progressive MTC with lymph node and liver metastases, which after 16 years of follow-up developed an ECS. After one month of 300 mg/day vandetanib treatment, a biochemical and clinical response of the ECS was achieved but it did not result in significant reduction of tumor burden. However the patient reached criteria for stable disease according to response evaluation criteria in solid tumors (RECIST 1.1) after 8 months of follow-up.

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Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative 131I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A 18FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors.

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In patients affected by differentiated thyroid cancer, the whole-body scan (WBS) with 131-radioiodine, especially when performed after a therapeutic activity of131I, represents a sensitive procedure for detecting thyroid remnant and/or metastatic disease. Nevertheless, a wide spectrum of potentially pitfalls has been reported. Herein we describe a 63-year-old woman affected by follicular thyroid cancer, who was accidentally found to have an abdominal mass at post-dose WBS (pWBS). pWBS showed abnormal radioiodine uptake in the upper mediastinum, consistent with lymph-node metastases, and a slight radioiodine uptake in an abdominal focal area. Computed tomography revealed an inhomogeneous mass in the pelvis, previously unrecognized. The lesion, surgically removed, was found to be a typical dermoid cyst of the ovary, without any evidence of thyroid tissue. By immunohistochemistry, a moderate expression of the sodium-iodine symporter (NIS) was demonstrated in the epithelial cells, suggesting a NIS-dependent uptake of radioiodine by the cyst.

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Thyroid pathology is rarely involved in the pathogenesis of sudden death in young people. We report here the cases of two young patients with decreased levels of thyroid hormones whose death was caused by an increased thrombotic status, with venous thrombosis and pulmonary thromboembolism. In both cases the thyroid pathology was not considered as the underlying cause of death as the association between this condition and venous thrombosis is still debatable. However its presence may be considered a circumstantial factor, which could increase the severity of the disease and subsequently the lethality rate in pulmonary thromboembolism. An increased awareness for hypothyroidism or subclinical hypothyroidism in clinical practice may lead to a decrease in mortality secondary to thromboembolic disease. Also, increased awareness for thyroid pathology during forensic autopsy in sudden deaths may lead to potentially significant results, that could explain some of the sudden death with an unknown cause, and decrease the number of the so called blank autopsies.

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Although hypothyroidism is associated with an increased prevalence of psychiatric manifestations, myxedema madness is rarely observed. We report the case of a 62-year-old woman with no prior history of psychiatric disorders, who presented to the emergency department with psychomotor agitation 6 weeks after total thyroidectomy for papillary thyroid cancer. Serum thyroid stimulating hormone (TSH) on admission was 62.9 mIU/L and free T4 was < 0.35 ng/dL, indicating severe hypothyroidism. After ruling out other possible causes, the diagnosis of myxedema madness was considered; hence, antipsychotic drug treatment and intravenous levothyroxine were prescribed. Behavioral symptoms returned to normal within 4 days of presentation, while levels of thyroid hormones attained normal values 1 week after admission. Recombinant TSH (Thyrogen®) was used successfully to prevent new episodes of mania due to thyroid hormone withdrawal in further controls for her thyroid cancer. This case illustrates that myxedema madness can occur in the setting of acute hypothyroidism, completely reverting with levothyroxine and antipsychotic treatment. Recombinant TSH may be a useful tool to prevent myxedema madness or any severe manifestation of levothyroxine withdrawal for the follow-up of thyroid cancer.

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Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary disorder. Here in, we report two patients with RTH in whom differentiated thyroid cancer was diagnosed. Two patients were admitted to our clinic and their laboratory results were elevated thyroid hormone levels with unsuppressed TSH. We considered this situation thyroid hormone resistance in the light of laboratory and clinical datas. Thyroid nodule was palpated on physical examination. Thyroid ultrasonography showed multiple nodules in both lobes. Total thyroidectomy was performed. The pathological findings were consistent with papillary thyroid microcarcinoma. BRAFV600E mutation analysis results were negative. RTH is very rare and might be overlooked. There is no consensus on how to overcome the persistently high TSH in patients with RTH and differentiated thyroid cancer (DTC). Further studies are needed to explain the relationship between RTH and DTC which might be helpful for the treatment of these patients.

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Introduction Undiagnosed hyperglycemia is common in high cardiovascular risk individuals, especially in those with coronary artery disease (CAD). There is no consensus about the optimal method for the screening of hyperglycemia in this population. Subjects and methods Five hundred and fourteen Brazilian individuals undergoing coronary angiography, without previously known diabetes mellitus (DM), had their glycemic status evaluated by both fasting plasma glucose (FPG) and HbA1c, being classified in normal (N), prediabetes (PD), and DM according to American Diabetes Association criteria. Concordance between both methods was assessed by Cohen’s κ. Accuracy of FPG and HbA1c to diagnose CAD was evaluated as proof-of-concept. Results Among individuals screened by FPG, 41.2% had PD and 6% had DM. Among those screened by HbA1c, 52.7% had PD and 12.7% had DM. Concordance for a positive screening of PD occurred in 125 individuals (κ = 0.084). Eighteen individuals had a concordant positive screening of DM (κ = 0.310). As a predictor of CAD, accuracy of FPG was 0.554 (p = 0.009) and of HbA1c 0.557 (p = 0.006). Conclusion a high frequency of hyperglycemia, between 47 and 65%, was found in individuals submitted to coronary angiography without previously known glucose disturbances, using FPG and HbA1c as screening methods respectively.HbA1c detected significantly more individuals with both PD and DM than FPG. Concordance between both methods is low. The question of which is the gold-standard method to diagnose hyperglycemia in this population is still open.