Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; = 0.020; 80% vs 50% at 10 years; = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.

SumárioA toxicidade de diversos poluentes ambientais em seres humanos e demais espécies tem sido habitualmente investigada quanto aos seus efeitos teratogênicos e cancerígenos. Nas últimas décadas, muitos contaminantes têm demonstrado efeitos adversos sobre o sistema endócrino. Atualmente, cerca de onze milhões de substâncias químicas são conhecidas em todo mundo, sendo três mil delas produzidas em larga escala. Numerosos compostos químicos de uso doméstico, industrial e agrícola possuem comprovada atividade hormonal. Entre os produtos químicos com atividade estrogênica, destacam-se hormônios presentes em cosméticos, anabolizantes utilizados em rações animais, fitoestrógenos e poluentes orgânicos persistentes (POPs). Esses agentes que estão presentes nos efluentes industriais, residenciais e das estações de tratamento de água e esgoto representam uma importante fonte de contaminação ambiental. O Programa Internacional de Segurança Química (International Programme on Chemical Safety − IPCS) define como interferente endócrino substâncias ou misturas presentes no ambiente capazes de interferir nas funções do sistema endócrino, causando efeitos adversos em um organismo intacto ou na sua prole. No presente artigo, os autores apresentam uma revisão da literatura atual sobre o papel desses elementos nas doenças endócrinas e metabólicas, os prováveis mecanismos de ação envolvidos, discutindo-se perspectivas futuras em termos de investigação e estratégias para prevenção e redução dos seus possíveis danos. Arq Bras Endocrinol Metab. 2010;54(1):6-16 Descritores Interferente endócrino; doenças endócrinas; mecanismo de ação; contaminantes ambientais; revisão SummaryThe toxicity of various pollutants has been routinely investigated according to their teratogenic and carcinogenic effects. In the last few decades, however, many of such pollutants have been shown to adversely affect the endocrine system of human beings and other species. Currently, more than eleven million chemical substances are known in the world, and approximately 3,000 are produced on a large scale. Numerous chemical composites of domestic, industrial and agricultural use have been shown to influence hormonal activity. Examples of such chemical products with estrogenic activity are substances used in cosmetics, anabolizing substances for animal feeding, phytoestrogens and persistent organic pollutants (POPs). These agents are seen in residential, industrial and urban sewerage system effluents and represent an important source of environmental contamination. The International Programme on Chemical Safety (IPCS) defines as endocrine disruptors substances or mixtures seen in the environment capable of interfering with endocrine system functions resulting in adverse effects in an intact organism or its offspring. In this article the authors present a current literature review about the role of these pollutants in endocrine and metabolic diseases, probable mechanisms of action, and suggest paths of investigation and possible strategies for prevention and reductio...

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Screening tests have been used to support a biochemical diagnosis of Cushing's syndrome (CS). Measurements of salivary cortisol offer facilities for studying out-patients. This study assessed salivary cortisol in screening for CS by evaluating hypercortisolism based on circadian rhythm and the overnight 1-mg dexamethasone (DEX) suppression test for out-patients. We evaluated 33 patients with CS. Thirty normal volunteers and 18 obese patients were used as controls. Salivary cortisol (nanograms per dL) levels (mean +/- SEM) were 596 +/- 44, 528 +/- 104, and 1205 +/- 118 (0900 h); 213 +/- 27, 325 +/- 76, and 778 +/- 74 (1700 h); and 95 +/- 8, 133 +/- 26, and 914 +/- 94 (2300 h) in normal controls, obese subjects, and CS patients, respectively. After the overnight 1-mg DEX test, they were 64 +/- 1.1, 107 +/- 25, and 1048 +/- 129, respectively. In the present series, a single out-patient 0900, 1700, and 2300 h measurement and an overnight 1-mg DEX salivary cortisol level above the 90th percentile of the control or obese group values had sensitivities of 65.6%, 81.8%, 100%, and 100% or 78.1%, 57.6%, 93.3%, and 91.4%, respectively. The sensitivity improved (100%) in response to the combination of 2300 h and overnight 1-mg DEX salivary cortisol suppression tests to differentiate between obese and CS subjects. Our data indicate that nighttime sample and overnight 1-mg DEX suppression salivary cortisol tests are sensitive markers for the diagnosis of CS. In addition, the combination of the two tests improves the ability to differentiate between obese and CS patients and may be useful for out-patient screening.

Objective: Although hypothyroidism has been linked to oxidative stress, data regarding the relationship between thyroid hormone levels and oxidative stress is still inconsistent. This study was designed to evaluate the effect of levothyroxine replacement on oxidative stress in women with primary hypothyroidism.Design: A total of 25 female patients with primary hypothyroidism were included. Oxidative stress markers were measured before and after levothyroxine replacement treatment in all patients.Methods: Oxidative stress was evaluated through the measurement of oxidants (thiobarbituric acid reactive substances [TBARS] and nitrite/nitrate levels), and antioxidants (superoxide dismutase and catalase activity).Results: Antioxidant catalase activity (63.77 ± 23.8 vs. 50.12 ±12.75 atv/min; p = 0.03) was significantly increased and the levels of TBARS (3.02 ± 0.86 vs. 3.55 ± 0.87 μM; p = 0.03) were significantly decreased in the state of euthyroidism after levothyroxine replacement compared to the hypothyroidism before levothyroxine treatment. No significant change in neither nitrite/nitrate concentration (p = 0.18) nor in superoxide dismutase activity (p = 0.93) after L-T4 adjustment was found.Conclusions: Our data demonstrate that levothyroxine replacement improved oxidative status in patients with primary hypothyroidism, indexed by the significantly decreased levels of malonaldehyde (MDA) and increased catalase (CAT) activity.

SUMMARYMany cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B-and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. Arq Bras Endocrinol Metab. 2012;56(9):677-82 SUMáRioMuitos casos têm sido publicados mostrando uma coexistência entre as doenças autoimunes da tireoide (DAIT) e outras doenças autoimunes. Cerca de um quarto dos pacientes com acalasia têm doenças da tireoide concomitantemente, sendo a mais comum a associação com hipotireoidismo. Apesar de ser relativamente rara, a associação da acalasia e hipertireoidismo requer atenção. A fisiopatologia da doença de Graves (DG) envolve os linfócitos B e T-mediados, os quais têm afinidade pelos antígenos da tireoide: tireoglobulina, tireoperoxidase e receptor de tireotrofina. Atualmente, a real fisiopatogenia da acalasia continua desconhecida. No entanto, alguns importantes achados em análise são sugestivos de mecanismo autoimune: infiltração significativa do plexo mioentérico pelos monócitos, presença do antígeno-DQwl do Complexo Humano de Histocompatibilidade classe II e presença de anticorpos contra neurô-nios mioentéricos. Este presente caso aborda um paciente que, apesar de testes negativos para doença de Chagas, tem acalasia que progrediu para o desenvolvimento de significativa perda ponderal e piora da sua qualidade de vida, posteriormente, diagnosticado com hipertireoidismo. Após dilatação endoscópica esofágica e ablação da glândula tireoide com radioiodo, houve grande melhora na condição clínica do paciente. Arq Bras Endocrinol Metab. 2012;56(9):677-82

Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.