Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione

Given the recent spate of reports of vitamin D deficiency, there is a need to reexamine our understanding of natural and other sources of vitamin D, as well as mechanisms whereby vitamin D synthesis and intake can be optimized. This state-of-the-art report from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society was aimed to perform this task and also reviews recommendations for sun exposure and vitamin D intake and possible caveats associated with these recommendations.

BACKGROUND: The prevalence of non-alcoholic fatty liver disease (NAFLD) has been increasing rapidly. It is nowadays recognized as the most frequent liver disease, affecting a quarter of global population and regularly coexisting with metabolic disorders such as type 2 diabetes, hypertension, obesity, and cardiovascular disease. In a more simplistic view, NAFLD could be defined as an increase in liver fat content, in the absence of secondary cause of steatosis. In fact, the clinical onset of the disease is a much more complex process, closely related to insulin resistance, limited expandability and dysfunctionality of adipose tissue. A fatty liver is a main driver for a new recognized liver-pancreatic α-cell axis and increased glucagon, contributing to diabetes pathophysiology. MAIN TEXT: This review will focus on the clinical and pathophysiological connections between NAFLD, insulin resistance and type 2 diabetes. We reviewed non-invasive methods and several scoring systems for estimative of steatosis and fibrosis, proposing a multistep process for NAFLD evaluation. We will also discuss treatment options with a more comprehensive view, focusing on the current available therapies for obesity and/or type 2 diabetes that impact each stage of NAFLD. CONCLUSION: The proper understanding of NAFLD spectrum-as a continuum from obesity to metabolic syndrome and diabetes-may contribute to the early identification and for establishment of targeted treatment.

Metabolic syndrome (MetS) and thyroid dysfunction are common in clinical practice. The objectives of this review are to discuss some proposed mechanisms by which thyroid dysfunctions may lead to MetS, to describe the bidirectional relationship between thyroid hormones (THs) and adiposity and finally, to resume a list of recent studies in humans that evaluated possible associations between thyroid hormone status and MetS or its clinical components. Not solely THs, but also its metabolites regulate metabolic rate, influencing adiposity. The mechanisms enrolled are related to its direct effect on adenosine triphosphate (ATP) utilization, uncoupling synthesis of ATP, mitochondrial biogenesis, and its inotropic and chronotropic effects. THs also act controlling core body temperature, appetite, and sympathetic activity. In a bidirectional way, thyroid function is affected by adiposity. Leptin is one of the hallmarks, but the pro-inflammatory cytokines and also insulin resistance impact thyroid function and perhaps its structure. MetS development and weight gain have been positively associated with thyroid-stimulating hormone (TSH) in several studies. Adverse glucose metabolism may be related to hyperthyroidism, but also to reduction of thyroid function or higher serum TSH, as do abnormal serum triglyceride levels. Hypo- and hyperthyroidism have been related to higher blood pressure (BP), that may be consequence of genomic or nongenomic action of THs on the vasculature and in the heart. In summary, the interaction between THs and components of MetS is complex and not fully understood. More longitudinal studies controlling each of all confounding variables that interact with endpoints or exposure factors are still necessary.

OBJECTIVE: It is believed that the variable effectiveness of somatostatin analogs in post-surgical management of somatotropinomas and non-functioning pituitary adenomas (NFPA) may be due in part to variable expression of somatostatin receptor isoforms (SSTR1-5), within and between pituitary tumor types. DESIGN AND METHODS: Quantitative real-time RT-PCR was used to compare absolute mRNA copy numbers for all five SSTR isoforms in 23 somatotropinomas and 19 NFPA. RESULTS: Somatostatin receptor subtype 5 mRNA was present at the highest level in somatotropinomas, followed by SSTR2>SSTR3>>SSTR1>>>SSTR4. In contrast, SSTR3 mRNA was present at the highest level in NFPA, followed by SSTR2, while SSTR1, SSTR4, and SSTR5 transcripts were only detectable in select tumors. Among somatotropinomas, a positive correlation was found between SSTR2 mRNA levels and the percent decrease of GH (%GH) after 3 and 6 months of therapy with octreotide long acting repeatable (LAR) (r=0.51 and r=0.66; P=0.05 and P=0.008). Also the percent decrease of IGF-I (%IGF-I) after 3 months of octreotide LAR was negatively correlated with SSTR5 and %IGF-I after 6 months of octreotide LAR was positively correlated with SSTR2. CONCLUSIONS: The present report is a large series examining SSTR mRNA levels in somatotropinomas and NFPA. These initial findings suggest that detailed knowledge of the SSTR mRNA expression profile in somatotropinomas can help to predict the hormonal response to therapy with LAR. Also, it appears that SSTR3 in NFPA may be a potential target for SSTR3 preferential or universal ligands such as pasireotide.

INTRODUÇÃO/OBJETIVOS: Descreve-se o processo de tradução e adaptação, para a língua portuguesa, da Binge Eating Scale (BES) -- Escala de Compulsão Alimentar Periódica (ECAP) --, que avalia a gravidade da compulsão alimentar periódica em indivíduos obesos. O objetivo foi traduzir, adaptar e avaliar a aplicabilidade da versão para o português da ECAP. MÉTODOS: Após cuidadoso processo de tradução e adaptação para a língua portuguesa, foi obtida uma versão final da ECAP. Para avaliar sua aplicabilidade, foi realizado um pré-teste em um grupo de 32 pacientes obesos com transtorno da compulsão alimentar periódica (TCAP) e que procuravam tratamento para emagrecer. RESULTADOS: Os pacientes compreenderam adequadamente os itens da ECAP. A média de pontuação da ECAP nos pacientes obesos com TCAP foi de 31,2 (±5,8). CONCLUSÃO: A versão final para o português da ECAP foi considerada adequada para uso clínico.

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.

OBJECTIVE: To determine whether the somatostatin receptor subtype (SSTR) expression profile correlates with hormonal and tumor volume responses to postsurgical octreotide long acting repeatable (OCT LAR) treatment. DESIGN AND METHODS: Quantitative real-time RT-PCR was used to evaluate the absolute mRNA copy numbers for all five SSTR subtypes in 22 somatotropinomas. Response to OCT LAR was studied by hormone levels (GH and IGF-I) and tumor volume (sella turcica magnetic resonance imaging). RESULTS: SSTR5 was present at the highest level followed by SSTR2, SSTR3, SSTR1, and SSTR4 (2327 (1046-5555), 2098 (194-23 954), 97 (0-460), 14 (0-29 480), and 0 (0-652) copies respectively). Positive correlations were found between SSTR2 levels and the percentage decrease of GH and IGF-I after 3 (r=0.49, P<0.027 and r=0.49, P<0.029 respectively) and 6 (r=0.59, P<0.006 and r=0.58, P<0.008 respectively) months of OCT LAR. A negative correlation was found between SSTR5 mRNA levels and the percentage decrease of GH after 3 months of OCT LAR (r=-0.52, P=0.016, n=21). A higher SSTR2/SSTR5 ratio was observed among patients who obtained hormonal control with OCT LAR, when compared with those uncontrolled (2.4 (0.7-10) vs 0.3 (0.1-7.7), P=0.001). A ROC curve analysis showed a SSTR2/SSTR5 ratio of 1.3 as the best predictor of disease control, with a sensitivity of 88% and a specificity of 92% - area under curve, 0.9. A positive correlation was also found between SSTR2 mRNA levels and the percentage decrease in tumor volume after 6 months of OCT LAR (r=0.79, P=0.002, n=12). CONCLUSIONS: Somatostatin receptor subtype 2 mRNA expression levels in somatotropinomas correlate positively with in vivo hormonal and tumor volume responses to OCT LAR.

Adolescent obesity is becoming a health problem in both developed and developing countries. Antiobesity drug therapy is not currently indicated for the treatment of adolescent obesity and remains investigational at this time. The aim of this study was to determine the efficacy and safety of sibutramine in obese adolescents. A randomized, double-blind, placebo-controlled trial, enrolling 60 adolescents, aged 14-17 yr, for 6 months was conducted. In the first month, all patients received placebo and a hypocaloric diet plus exercise orientation. For the next 6 months, participants received either sibutramine or placebo. Patients assigned to sibutramine group lost an average of 10.3 +/- 6.6 kg, and patients in placebo group lost 2.4 +/- 2.5 kg (P < 0.001). The mean body mass index reduction was significantly greater in the sibutramine group (3.6 +/- 2.5 kg/m(2)) than in the placebo group (0.9 +/- 0.9 kg/m(2); P < 0.001). No participant withdrew because of adverse events, and no difference in blood pressure or heart rate was noted between groups. There were no changes in echocardiographic parameters. In conclusion, sibutramine plus diet and exercise induced significantly more weight loss in obese adolescents.

OBJECTIVE: The aim of this study was to assess executive functions of obese individuals with binge eating disorder. METHOD: Thirty-eight obese individuals with binge eating disorder were compared to thirty-eight obese controls without binge eating disorder in terms of their executive functions. All individuals were assessed using the following instruments: Digit Span, Trail Making Tests A and B, Stroop Test and the Wisconsin Card Sorting Test. In addition, four subtests from the Behavioral Assessment of the Dysexecutive Syndrome Battery were also used, namely the Zoo Map Test, the Modified Six Elements Test, the Action Program Test and the Rule Shift Cards Test. RESULTS: When compared to obese controls, obese individuals with binge eating disorder presented significant impairment in the following tests: Digit Span backward, Zoo Map Test, Modified Six Elements Test, and Action Program Test. Subjects with binge eating disorder also showed significant more set shifting and perseverative errors in the Wisconsin Card Sorting Test. In other measures such as the Digit Span Forward, the Trail Making Test, the Stroop Test and the Rule Shift Cards Test, obese subjects with binge eating disorder did not differ significantly from obese subjects without binge eating disorder. CONCLUSION: These results suggest that, in the present sample, obese individuals with binge eating disorder presented executive deficits, especially impairments relating to problem-solving, cognitive flexibility and working memory.

1. Introducao Esta cientificamente comprovado, sendo algo incorporado ao senso comum, que ser fisicamente ativo contribui para preservar e recuperar a boa saude do corpo e da mente. Os efeitos favoraveis da reabilitacao cardiovascular (RCV) com enfase nos exercicios fisicos tem sido consistentemente documentados, inclusive em meta-analises de estudos clinicos randomizados, que demonstram significativas reducoes da morbimortalidade cardiovascular e global, bem como da taxa de hospitalizacao, , com expressivo ganho de qualidade de vida, , justificando a sua consensual e [...]

Chlorpropamide was given to 3 patients with idiopathic diabetes insipidus and 2 with nephrogenic diabetes insipidus. Its influence on urine flow, “free” water and osmolal clearances as well as on blood sugar was studied. A sharp antidiuretic response was observed in the first 3 patients. Although the antidiuretic mechanism of chlorpropamide is not yet known, there is a strong suggestion that it acts in a way similar to that of the antidiuretic hormone, at least in some respects. The possibility of the use of chlorpropamide in the treatment of idiopathic diabetes insipidus is suggested.

CONTEXT: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. OBJECTIVES: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1-5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. DESIGN AND PATIENTS: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. RESULTS: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T>>>DR4>>DR5>DR1, whereas in NFPAs, DR2T>>>DR4>>DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = -0.67, P = 0.002; and 6 months: r = -0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). CONCLUSIONS: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5.

BBackground: Currently the treatment of nonalcoholic fatty liver disease (NAFLD) is based on weight loss through lifestyle changes, such as exercise combined with calorie-restricted dieting. Objectives: To assess the effects of a commercially available weight loss program based on a Very Low-Calorie Ketogenic Diet (VLCKD) on Visceral Adipose Tissue (VAT) and liver fat content compared to a standard Low-Calorie diet (LC). As a secondary aim we evaluated the effect on liver stiffness measurements. Methods: Open, randomized, controlled, prospective pilot study. Patients were randomized and treated either with a LC or a VLCKD and received orientation and encouragement to physical activity equally for both groups. VAT, liver fat fraction and liver stiffness were measured at baseline and after 2 months of treatment using Magnetic Resonance Imaging (MRI). Paired t-tests were used for comparison of continuous variables between visits and unpaired test between groups. Categorical variables were compared using the Chi-squared test. Pearson’s correlation was used to assess the association between VAT, anthropometric measures and hepatic fat fraction. A significance level of the results was established at p&lt;0.05. Results: 39 patients (20 with VLCKD and 19 with LC) were evaluated at baseline and 2 months of intervention. Relative weight loss at 2 months was -9.59 ± 2.87 % in the VLCKD group and -1.87 ± 2.4 % in the LC group (p&lt;0.001). Mean reductions in VAT were -32.0 cm2 for VLCKD group and -12.58 cm2 for LC group (p&lt;0.05). Reductions in liver fat fraction were significantly more pronounced in the VLCKD group than in LC group (4.77% vs 0.79%; p&lt;0.005). Conclusion: Patients undergoing a VLCKD achieved superior weight loss, with significant VAT and liver fat fraction reductions when compared to standard the low-calorie diet. The weight loss and rapid mobilization of liver fat demonstrated with VLCKD, could serve as an effective alternative for the treatment of NAFLD.

This article estimates the burden of hospitalization associated with overweight and obesity in Brazil. The analysis of all hospitalizations for men and women from 20 to 60 years of age was based on the National Healthcare Expenditure Database (SIH-SUS), covering more than 70% of all hospital admissions. Data were for the year 2001. Attributable fraction of hospitalizations associated with diseases related to obesity and overweight was based on the combined risks of United States and European cohorts. The population-attributable fraction for each disease studied was multiplied by values reimbursed to the hospitals and summed to obtain total direct costs. Overall costs of overweight and obesity represent 3.02% of total hospitalization costs for men and 5.83% for women, corresponding to 6.8 and 9.3% of all hospitalization (excluding pregnancy). Diseases associated with overweight and obesity had a significant impact on hospitalizations and economic costs in Brazil, and overall percentages were similar to those from developed countries. Since the nutritional transition is still under way in Brazil, overweight had a higher impact than obesity on disease prevalence and costs.

Abstract Background Giant prolactinomas are an unusual subset of macroprolactinomas and are more commonly found in men. The goal of this review is to propose a giant prolactinoma definition and discuss the available therapeutic options for biochemical and tumour volume control. Methods A comprehensive search of all published studies was performed between A pril and N ovember 2012 in electronic databases ( P ub M ed and O vid). Results A giant prolactinoma should be defined as an adenoma with a maximum diameter of more than 4 cm that is associated with serum prolactin above 5300 mIU /l. Regarding treatment, cabergoline is the preferred dopamine agonist for medical management of giant prolactinomas because of its excellent efficacy and tolerability. Normalization of prolactin level and significant tumour reduction may be achieved in the majority of patients. Combined therapy, particularly cabergoline and surgery, may be necessary due to the large tumour load. Radiotherapy and temozolomide may be used for patients with aggressive giant prolactinomas in whom tumour volume control is not achieved with cabergoline and surgery. Conclusion There is a scarcity of large studies about the management of giant prolactinoma. Cabergoline is the first‐line treatment. However, caution should be exercised when comparing efficacy rates among the different treatment modalities due to the variability in study design and data quality. In this scenario, a ‘standard’ definition for giant prolactinomas and larger series may be helpful to assess the real efficacy and safety of each therapeutic modality.

Metabolic syndrome is an important risk factor for cardiovascular disease. Adipokines interfere with insulin action and endothelial cell function. We investigated the relationship among adipokines, metabolic factors, inflammatory markers, and vascular reactivity in obese subjects with metabolic syndrome and lean controls. Cross-sectional study of 19 obese subjects with metabolic syndrome and 8 lean volunteers evaluated as controls. Vascular reactivity was assessed by venous occlusion pletysmography measuring braquial forearm blood flow (FBF) and vascular resistance (VR) responses to intra-arterial infusions of endothelium-dependent (acetylcholine-Ach) and independent (sodium nitroprusside-SNP) vasodilators. Blood samples were obtained to evaluate C reactive protein (CRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, adiponectin, resistin, and lipid profile. Patients were classified with regard to insulin resistance through the HOMA-IR index. PAI-1, CRP and fibrinogen were higher and adiponectin was lower in metabolic syndrome subjects compared to controls. Metabolic syndrome subjects had impaired vascular reactivity. Adiponectin and PAI-1 were associated with insulin, HOMA-IR, triglycerides, and HDLc; and resistin with CRP. Adiponectin was associated with VR after Ach in the pooled group and resistin with D FBF after Ach in the metabolic syndrome group. Metabolic syndrome subjects exhibited low levels of adiponectin and high levels of CRP, fibrinogen, and PAI-1. Adiponectin and PAI-1 correlated with insulin resistance markers. Adiponectin and resistin correlated with vascular reactivity parameters. An adipocyte-endothelium interaction might be an important mechanism of inflammation and vascular dysfunction. A Síndrome Metabólica é um importante fator de risco para doenças cardiovasculares. As adipocinas interferem com a ação da insulina e com a função endotelial. Investigar a relação entre adipocinas, fatores metabólicos, marcadores inflamatórios e reatividade vascular para inferência da função endotelial em pacientes obesos e controles magros. Estudo transversal de 19 pacientes obesos com Síndrome Metabólica e 8 controles magros. A reatividade vascular foi avaliada pela pletismografia de oclusão venosa medindo o fluxo sangüíneo da artéria braquial e sua resistência vascular a partir de infusões intra-arteriais de vasodilatadores endotélio-dependente (acetilcolina) e endotélio-independente (nitroprussiato de sódio). Foram também avaliados no sangue a proteína C reativa (PCR), o inibidor do ativador do plasminogênio 1 (PAI-1), fibrinogênio, adiponectina, resistina e o perfil lipídico. Os pacientes foram classificados quanto à resistência insulínica pelo índice HOMA-IR. PAI-1, PCR e fibrinogênio apresentaram valores mais altos e a adiponectina mais baixos para os pacientes com Síndrome Metabólica do que com os controles. Pacientes com Síndrome Metabólica apresentaram prejuízo da reatividade vascular. A adiponectina e PAI-1 estiveram associadas à insulina, HOMA-IR, triglicerídeos e HDLc; e resistina com o PCR. Adiponectina esteve associada com a resistência vascular e a resistina com o fluxo sangüíneo depois da acetilcolina em pacientes com Síndrome Metabólica. Pacientes com Síndrome Metabólica exibiram baixas concentrações sangüíneas de adiponectina e altos níveis de PCR, fibrinogênio e PAI-1. Adiponectina e PAI-1 correlacionaram com os marcadores da resistência insulínica. Adiponectina e resistina correlacionaram com a reatividade vascular. A interação adipócito-endotélio vascular pode ser um importante mecanismo de inflamação e disfunção vascular.

A obesidade, condição cuja prevalência vem aumentando em níveis de epidemia no mundo inteiro, compartilha com os transtornos psiquiátricos de pesado preconceito tanto entre a população leiga quanto entre os profissionais de Saúde. Quando se considera a associação entre estas patologias, observa-se uma pobreza de dados quer em termos caracterização desta associação quer em termos de tratamentos específicos. Neste artigo, tópicos relativos à interface entre estes aspectos e a realização de operações bariátricas, assim como um breve resumo de suas indicações serão abordados, à luz da literatura mundial e da experiência dos autores.

BACKGROUND: The pathophysiology of eating disorders is still unknown, with many factors possibly involved. The existence of a central nervous system (CNS) dysfunction is being investigated with particular interest. One of the most employed strategies to reach this goal is the evaluation of cognitive functioning of patients with eating disorders with neuropsychological tests. OBJECTIVE: To evaluate the current knowledge about the neuropsychology of ED. METHODS: We performed a review of several data bases (including MedLINE, PsychoINFO, LILACS and Cochrane Data Bank), using terms related to main theme of interest. The review comprised articles published up to January, 2004. RESULTS: Anorexia Nervosa (AN) was the most studied ED from the neuropsychological point-of-view, with studies tending to elicit attentive, visuo-spatial, and visuo-constructive deficits among such patients. On the other side, patients with Bulimia Nervosa (BN) exhibited deficits in the selective aspects of attention and in executive functions. As yet, there is no study covering the neuropsychological aspects of binge-eating disorder. After successful treatment, individuals show improvement of some cognitive deficits, while other seem to persist. CONCLUSIONS: The ED are possibly associated with a certain degree of neuropsychological dysfunction, even though there is no consensus with regard to which function is particularly impaired. The fact that some cognitive dysfunction tend to disappear after treatment argues in favor of the hypothesis that these are functional deficits. Other deficits, however, tend to persist, suggesting that they may precede the development of eating disorders or even contribute to their development or to a worse prognosis. The study of the neuropsychological aspects of ED may help tailoring more selective therapeutic approaches to patients suffering from these disorders.

BACKGROUND: Comorbid depression in diabetes has been suggested as one of the possible causes of an inadequate glycemic control. The purpose of this study was to investigate the association between major depression and the glycemic control of type 2 diabetes mellitus (T2DM). METHODS: Seventy T2DM patients were evaluated. They underwent a psychiatric examination using the following instruments: Structured Clinical Interview for DSM-IV and Beck Depression Inventory. The diabetes status was assessed in the short-term (glycemia, glycated hemoglobin) clinical control. RESULTS: The presence of current depression was observed in 18.6% (13/70). In addition, type 2 diabetes patients who displayed depression evidenced higher levels of glycated hemoglobin (8.6 ± 2.0 vs. 7.5 ± 1.8; p = 0.05) when compared to those who did not exhibit a mood disorder. CONCLUSIONS: In our sample, the presence of depression seems to impact on the short-term control of T2DM. The authors discuss the clinical utility of these findings in the usual treatment of diabetes.

Hypercortisolism is associated with various systemic manifestations, including central obesity, arterial hypertension, glucose intolerance/diabetes mellitus, dyslipidemia, nephrolithiasis, osteoporosis, gonadal dysfunction, susceptibility to infections, psychiatric disorders, and hypercoagulability. The activation of the hemostatic system contributes to the development of atherosclerosis and subsequent cardiovascular morbidity and mortality. Previous studies have identified an increased risk of both unprovoked and postoperative thromboembolic events in patients with endogenous and exogenous Cushing's syndrome (CS). The risk for postoperative venous thromboembolism in endogenous CS is comparable to the risk after total hip or knee replacement under short-term prophylaxis. The mechanisms that are involved in the thromboembolic complications in hypercortisolism include endothelial dysfunction, hypercoagulability, and stasis (Virchow's triad). It seems that at least two factors from Virchow's triad must be present for the occurrence of a thrombotic event in these patients. Most studies have demonstrated that this hypercoagulable state is explained by increased levels of procoagulant factors, mainly factors VIII, IX, and von Willebrand factor, and also by an impaired fibrinolytic capacity, which mainly results from an elevation in plasminogen activator inhibitor 1. Consequently, there is a shortening of activated partial thromboplastin time and increased thrombin generation. For these reasons, anticoagulant prophylaxis might be considered in patients with CS whenever they have concomitant prothrombotic risk factors. However, multicenter studies are needed to determine which patients will benefit from anticoagulant therapy and the dose and time of anticoagulation.