Manoel Ricardo Alves Martins

Contaminantes ambientais e os interferentes endócrinos

The 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 reduction of its possible damages.

Diagnosis of subclinical central hypothyroidism in patients with hypothalamic-pituitary disease by Doppler echocardiography

OBJECTIVE The diagnosis of subclinical central hypothyroidism in hypothalamic-pituitary patients cannot be established by serum markers of thyroid hormone action. Myocardial function by echocardiography has been shown to reflect thyroid hormone action in primary thyroid dysfunction. We evaluated the performance of echocardiography in diagnosing subclinical central hypothyroidism. DESIGN Cross-sectional and before and after. METHODS Echocardiography and serum thyroid hormones were assessed in overt primary (n=20) and central (n=10) hypothyroidism, subclinical primary hypothyroidism (n=10), hypothalamic-pituitary disease with normal free thyroxine (FT(4); n=25), and controls (n=28). Receiver operating characteristic (ROC) curves were generated using overt hypothyroidism patients and selected cut-off values were applied to detect both primary and central subclinical hypothyroidism. After levothyroxine (l-T(4)) intervention, patients were echocardiographically reevaluated at predefined targets: normal thyrotropin (TSH) in primary hypothyroidism, normal FT(4) in overt central hypothyroidism, and higher than pretreatment FT(4) in echo-defined subclinical central hypothyroidism. RESULTS Parameters with highest areas under the ROC curves (area under the curve (AUC) ≥0.94) were as follows: isovolumic contraction time (ICT), ICT/ejection time (ET), and myocardial performance index. Highest diagnostic accuracy (93%) was obtained when at least one parameter was increased (positive and negative predictive values: 93%). Hypothyroidism was echocardiographically diagnosed in eight of ten patients with subclinical primary hypothyroidism and in 14 of 25 patients (56%) with hypothalamic-pituitary disease and normal serum FT(4). Echocardiographic abnormalities improved significantly after l-T(4) and correlated (0.05<P<0.001) with changes in FT(4) (-0.62<r<-0.55) and TSH (0.63<r<0.68) in primary hypothyroidism and with FT(4) in central hypothyroidism (-0.72<r<-0.50). CONCLUSION Echocardiography can be useful in diagnosing subclinical central hypothyroidism in patients with hypothalamic-pituitary disease.

HFE gene mutation and oxidative damage biomarkers in patients with myelodysplastic syndromes and its relation to transfusional iron overload: an observational cross-sectional study

Objective A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. Design, setting and participants An 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. Methods IOL 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. Results The 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. Conclusions We 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 number Local Ethics Committee (licence 150/2009).

Increased parameters of oxidative stress and its relation to transfusion iron overload in patients with myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are group of stem cell disorders characterised by peripheral cytopaenias and a variable risk of progression to acute myeloid leukaemia. Most patients have anaemia and many develop transfusion dependence and iron overload (IOL), considered to be a negative independent prognostic factor associated with a higher risk of leukemic transformation and shorter survival.1 Iron pool is regarded as an important regulator of the production of reactive oxygen species (ROS). The excessive production of ROS and reactive nitrogen species causes lipid peroxidation, which can suppress self-renewal, the number of haematopoietic stem cells and directly induce DNA damage and genomic instability.2 However, the role of iron-mediated oxidative stress in the physiopathology of MDS remains uncertain. The present study aimed to evaluate plasma nitrite (NO2 −) and plasma malonaldehyde, secondary product of lipid peroxidation, in patients with MDS and correlate them with IOL due to transfusion dependence in MDS patients. Consecutive adult patients with MDS with and without IOL, followed at the University Hospital of the Federal University of Ceara, Brazil, were enrolled. The study was approved by the local ethics committee (licence 150/2009). They were classified according to the presence or absence of IOL defined as serum ferritin of 1000 ng/ml or …

Tissue doppler echocardiography detects preclinical markers of cardiac lesion in MDS patients

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.

Influência dos níveis séricos de IGF-I e de testosterona sobre o perfil lipídico e glicêmico em homens acromegálicos

OBJECTIVES: To evaluate the influence of IGF-I and testosterone on the lipid profile and glycemia in acromegalic men. METHODS: Fifteen acromegalic men were studied. RESULTS: The hypogonadic patients presented lower HDL-c and higher tryglicerides, LDL-c, glycemia, GH and IGF-I. Serum IGF-I was inversely correlated with HDL-c (r = - 0.57, p = 0.04) and directly with TG (r = 0.62, p = 0.01) and glycemia (r = 0.66, p = 0.008), whereas serum testosterone correlated directly with HDL-c (r = 0.52, p = 0.05) and inversely with TG (r = - 0.57, p = 0.02), LDL-c (r = - 0.53, p = 0.04) and fasting blood glucose (r = - 0.54, p = 0.03). IGF-I and testosterone were inversely correlated (r = - 0.585, p = 0.028). CONCLUSION: These results suggest that the most important intervention in reducing cardiovascular risk in these patients is to control the activity of the disease.

hGH treatment impact on adrenal and thyroid functions

Somatotrophic status is a major determinant of both thyrotrophic and corticotrophic axis. In growth hormone deficient patients, somatotrophic replacement increases the conversion rate of the inactive form of the thyroid hormone (T4) to its active form (T3), whereas the same replacement induces the conversion of cortisol, which is hormonally active, in cortisone, its inactive form. This review details the effects of GH on these two hormonal axis, possible mechanisms and clinical implications for the management of hypopituitary patients.