Objective: Nearly 40% of acromegalic patients fail to control GH/IGF-I levels with somatostatin analogues (SA). Dopaminergic agonists (DA) are even less effective, but combination therapy with SA and DA normalizes IGF-I levels in 33–56% of patients not controlled by octreotide alone in short-term studies. This study was designed to evaluate short- and long-term efficacy of cabergoline in controlling IGF-I levels in acromegalic patients receiving octreotide. Design: Open-label, single arm, prospective trial. Nineteen patients (14 females, 29–78 years of age) with high IGF-I on octreotide-LAR (30 mg/month IM) for ≧6 months were enrolled. Study I: Cabergoline (PO) was started at 1.0, increased to 2.0 and 3.5 mg/week, and withdrawn at 6-week intervals. IGF-I, GH, and PRL were measured at baseline and at 6-week intervals. Study II: Responder patients (IGF-I ≤1 ULN) resumed cabergoline at individual lowest effective doses and were evaluated at 6-month intervals for ≧12 months. Study III: Responders were withdrawn from octreotide and hormonally evaluated at 3-month intervals. Methods: Serum IGF-I (IRMA), GH (ICMA) and PRL (ICMA) levels were determined by commercially available kits. Results: Addition of cabergoline to octreotide-LAR normalized IGF-I levels in 7 of 19 patients (37%) during both short- and long-term follow-up (12–27 months, mean: 18 months). Octreotide withdrawal increased IGF-I levels in only 2 of 6 responder patients. Normalization of IGF-I levels by cabergoline was strongly associated with IGF-I ≤2.2 ULNR and/or GH ≤4.0 ng/ml under octreotide treatment. Conclusion: Addition of cabergoline to octreotide was effective in both short- and long-term control of IGF-I in acromegaly, especially in patients with mild/moderately elevated GH/IGF-I levels during octreotide.

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...

ObjectiveA relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated.Design, setting and participantsAn observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011.MethodsIOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry.ResultsThe HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11 649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions.ConclusionsWe observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress.Trial registration numberLocal Ethics Committee (licence 150/2009).

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Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

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.

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders characterized by ineffective hematopoiesis that leads to cytopenias and an increased risk of evolution to acute myeloid leukemia. Median age at diagnosis is around 70 years and therefore patients frequently have comorbid conditions that potentially influence outcome and treatment approaches, beyond the risk stratification established by the revised International Prognostic Scoring System (IPSS-R). The integration of comorbidity assessment to traditional risk stratification was shown to improve prognostic accuracy in MDS [1]. Age is also a critical risk factor for the development of malnutrition and frailty, all non-disease-related characteristics that impact prognosis. Frailty is a clinical syndrome associated with weakness, lower activity, vulnerability, and has been associated with poor health outcomes: poor response and tolerability to treatment and shorter survival. Routine frailty assessment is, therefore, strongly recommended when evaluating patients with MDS [2] Frailty and malnutrition, have both been considered as non-hematologic predictors of mortality, improving the prognostic value of the commonly used prognostic scoring system for MDS, associated with chemotherapy toxicity and mortality in older adults [3,4].

Myelodysplastic syndrome (MDS) is a clonal hematopoietic stem cell disorder of elderly people. Cardiac dysfunction is a marker of grim prognosis in MDS. We evaluated cardiac dysfunction of MDS patients with or without transfusion dependency by tissue doppler echocardiography. We found the average values of ventricular end-systolic and end-diastolic volumes in transfusion dependency MDS group higher than others. These results were strongly correlated to hemoglobin levels. Tissue Doppler Echocardiography should be routinely performed in MDS patients to detect preclinical cardiac alterations and prevent more heart insults in this group of chronic anemic aged patients.