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Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare, potentially fatal complication of SARS-CoV-2 infection. Genetic defects in inflammation-related pathways have been linked to MIS-C, but additional research is needed, especially in diverse ethnic groups. The present study aimed to identify genetic variants underlying MIS-C in Brazilian patients. Whole-exome sequencing was performed, focusing on genes involved in the host immune response to SARS-CoV-2. Functional assays assessed the impact of selected variants on NF-κB signaling. Nine rare, potentially deleterious variants were found in eight of 21 patients, located in IL17RC, IFNA10, or NLRP12 genes. Unlike the wild-type NLRP12 protein, which inhibits NF-κB activation in HEK 293T cells, the mutant NLRP12 proteins have significantly reduced inhibitory properties. In conclusion, our results indicate that rare autosomal variants in immune-related genes may underlie MIS-C, highlighting the potential role of NLRP12 in its predisposition. These findings provide new insights for the appropriate management of MIS-C., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Determining the etiology of hyperprolactinemia is fundamental for selecting the most appropriate treatment strategy. The aim of this study was to evaluate the usefulness and accuracy of prolactin levels in predicting the etiology of nonphysiological hyperprolactinemia., Subjects and Methods: In this retrospective study, we reviewed medical records of patients with nonphysiological hyperprolactinemia seen at two neuroendocrine reference centers located in Recife, Brazil, from January 2000 to December 2019., Results: The study included 770 patients aged 12-73 years (65% female). The three most frequent etiologies of hyperprolactinemia were prolactinomas (n = 263; 34.2%), drug-induced hyperprolactinemia (n = 160; 20.8%), and macroprolactinemia (n = 120; 15.6%). The highest mean prolactin levels were observed in cases of prolactinomas and idiopathic hyperprolactinemia. Most patients with hyperprolactinemia due to other etiologies had prolactin levels < 100 ng/mL, but these levels were also found in 16.5% of patients with microproplactinomas and in 20% of those with idiopathic hyperprolactinemia. Likewise, prolactin levels largely overlapped among patients with microprolactinomas, macroprolactinemia, and drug-induced hyperprolactinemia. Notably, prolactin levels > 250 ng/mL enabled a clear distinction between the etiologies of macroprolactinoma and nonfunctioning pituitary adenoma. Moreover, prolactin levels > 500 ng/mL were highly suggestive of macroprolactinomas, although they were also found in very few patients (<2%) with microprolactinomas or drug-induced hyperprolactinemia., Conclusion: Despite considerable overlap in prolactin levels among the different etiologies of hyperprolactinemia, values > 250 ng/mL allowed a clear distinction between macroprolactinomas and nonfunctioning pituitary adenomas. Furthermore, prolactin levels > 500 ng/mL were almost exclusively found in patients with prolactinomas., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Background: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020., Methods: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria., Results and Conclusions: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m 2 . SGLT2 inhibitors can be continued until end-stage kidney disease., (© 2023. The Author(s).)

Homozygosity for the common ACTN3 null polymorphism ( ACTN3 577X) results in α-actinin-3 deficiency in ~20% of humans worldwide and is linked to reduced sprint and power performance in both elite athletes and the general population. α-Actinin-3 deficiency is also associated with reduced muscle mass, increased risk of sarcopenia, and altered muscle wasting response induced by denervation and immobilization. Here, we show that α-actinin-3 plays a key role in the regulation of protein synthesis and breakdown signaling in skeletal muscle and influences muscle mass from early postnatal development. We also show that α-actinin-3 deficiency reduces the atrophic and anti-inflammatory response to the glucocorticoid dexamethasone in muscle and protects against dexamethasone-induced muscle wasting in female but not male mice. The effects of α-actinin-3 deficiency on muscle mass regulation and response to muscle wasting provide an additional mechanistic explanation for the positive selection of the ACTN3 577X allele in recent human history., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Background/objectives: Admixed populations are a resource to study the global genetic architecture of complex phenotypes, which is critical, considering that non-European populations are severely underrepresented in genomic studies. Here, we study the genetic architecture of BMI in children, young adults, and elderly individuals from the admixed population of Brazil., Subjects/methods: Leveraging admixture in Brazilians, whose chromosomes are mosaics of fragments of Native American, European, and African origins, we used genome-wide data to perform admixture mapping/fine-mapping of body mass index (BMI) in three Brazilian population-based cohorts from Northeast (Salvador), Southeast (Bambuí), and South (Pelotas)., Results: We found significant associations with African-associated alleles in children from Salvador (PALD1 and ZMIZ1 genes), and in young adults from Pelotas (NOD2 and MTUS2 genes). More importantly, in Pelotas, rs114066381, mapped in a potential regulatory region, is significantly associated only in females (p = 2.76e-06). This variant is rare in Europeans but with frequencies of ~3% in West Africa and has a strong female-specific effect (95% CI: 2.32-5.65 kg/m 2 per each A allele). We confirmed this sex-specific association and replicated its strong effect for an adjusted fat mass index in the same Pelotas cohort, and for BMI in another Brazilian cohort from São Paulo (Southeast Brazil). A meta-analysis confirmed the significant association. Remarkably, we observed that while the frequency of rs114066381-A allele ranges from 0.8 to 2.1% in the studied populations, it attains ~9% among women with morbid obesity from Pelotas, São Paulo, and Bambuí. The effect size of rs114066381 is at least five times higher than the FTO SNPs rs9939609 and rs1558902, already emblematic for their high effects., Conclusions: We identified six candidate SNPs associated with BMI. rs114066381 stands out for its high effect that was replicated and its high frequency in women with morbid obesity. We demonstrate how admixed populations are a source of new relevant phenotype-associated genetic variants.

Objective: To evaluate the maternal-fetal outcomes of CAB-induced pregnancies in patients with prolactinoma in a large cohort., Methods: The prevalence of tumor growth, miscarriage, preterm, low birth weight, congenital malformations and impairment in neuropsychological development in children among women treated with CAB were assessed in a Brazilian multicentre retrospective observational study, RESULTS: We included 194 women with a mean age of 31 (17-45) years, 43.6% presenting microadenomas and 56.4% macroadenomas, at prolactinoma diagnosis. In 233 pregnancies, CAB was withdrawn in 89%, after pregnancy confirmation. Symptoms related to tumor growth occurred in 25 cases, more frequently in macroadenomas. The overall miscarriage rate was 11%, although higher in the subgroup of patients with CAB maintainance after pregnancy confirmation (38% vs. 7.5%). Amongst the live-birth deliveries, preterm occurred in 12%, low birth weight in 6% and congenital malformations in 4.3%. Neuropsychological development impairment was reported in 7% of cases., Conclusions: Our findings confirm previous results of safety in maternal and fetal outcomes in CAB-induced pregnancies; nevertheless, CAB maintenance after pregnancy confirmation was associated with higher miscarriage rate; result that must be further confirmed.

Background: Human fertility has always been a topic of curiosity and devotion. Many cultures consider fertility to be a necessity for the survival and perpetuation of mankind and since early times, myths were created to explain this fabulous process. Fertility gods were ubiquitous in numerous ancient human cultures and were used both to understand fertility and to cope with infertility by means of rituals and offerings., Objectives: This manuscript aims to catalog and describe the deities associated with male fertility and virility., Material and Methods: We conducted a comprehensive search for the terms "male fertility god" and "male virility god" on the internet using web-based search engines. Based on the information retrieved, we selected those deities directed related to male fertility and/or virility and further deepened the search using Pubmed and Medline databases for peer-reviewed articles as well as books and articles about ancient mythology., Results: We identified several gods linked to male fertility and virility in various cultures from Egypt, Greece, Rome, India, Southwestern United States, France, Colombia and Buthan.., Discussion: Most of these deities were depicted with an erect phallus and with other fertility symbols like snakes. Some deities were also associated with plants and/or animal fertility and their festivals were often held during the harvest period., Conclusion: Gods of male fertility and virility played important roles in many ancient cultures. Offerings and rituals to these gods were the only available options to deal with problems of reproduction and demonstrate the lengths to which ancient people would go seeking cures for infertility., (© 2019 American Society of Andrology and European Academy of Andrology.)

An appropriate diagnostic evaluation is essential for the most appropriate treatment to be performed. Currently, macroprolactinemia is the third most frequent cause of nonphysiological hyperprolactinemia after drugs and prolactinomas. Up to 40% of macroprolactinemic patients may present with hypogonadism symptoms, infertility, and/or galactorrhea. Thus, the screening for macroprolactin is indicated not only for asymptomatic subjects but also for those without an obvious cause for their prolactin (PRL) elevation. Before submitting patients to macroprolactin screening and pituitary magnetic resonance imaging, one should rule out pregnancy, drug-induced hyperprolactinemia, primary hypothyroidism, and renal failure. The magnitude of PRL elevation can be useful in determining the etiology of hyperprolactinemia. PRL values >250 ng/mL are highly suggestive of prolactinomas and virtually exclude nonfunctioning pituitary adenomas (NFPAs) and other sellar masses as the etiology of hyperprolactinemia. However, they can also be found in subjects with macroprolactinemia, drug-induced hyper-prolactinemia or chronic renal failure. By contrast, most patients with NFPAs, drug-induced hyperprolactinemia, macroprolactinemia, or systemic diseases present with PRL levels <100 ng/mL. However, exceptions to these rules are not rare. Indeed, up to 25% of patients harboring a microprolactinoma or a cystic macroprolactinoma may also have PRL <100 ng/mL. Falsely low PRL levels may result from the so-called "hook effect," which should be considered in all cases of large (≥3 cm) pituitary adenomas associated with normal or mildly elevated PRL levels (≤250 ng/mL). The hook effect may be unmasked by repeating PRL measurement after a 1:100 serum sample dilution., (© 2019 S. Karger AG, Basel.)

Loss of expression of ACTN3, due to homozygosity of the common null polymorphism (p.Arg577X), is underrepresented in elite sprint/power athletes and has been associated with reduced muscle mass and strength in humans and mice. To investigate ACTN3 gene dosage in performance and whether expression could enhance muscle force, we performed meta-analysis and expression studies. Our general meta-analysis using a Bayesian random effects model in elite sprint/power athlete cohorts demonstrated a consistent homozygous-group effect across studies (per allele OR = 1.4, 95% CI 1.3-1.6) but substantial heterogeneity in heterozygotes. In mouse muscle, rAAV-mediated gene transfer overexpressed and rescued α-actinin-3 expression. Contrary to expectation, in vivo "doping" of ACTN3 at low to moderate doses demonstrated an absence of any change in function. At high doses, ACTN3 is toxic and detrimental to force generation, to demonstrate gene doping with supposedly performance-enhancing isoforms of sarcomeric proteins can be detrimental for muscle function. Restoration of α-actinin-3 did not enhance muscle mass but highlighted the primary role of α-actinin-3 in modulating muscle metabolism with altered fatiguability. This is the first study to express a Z-disk protein in healthy skeletal muscle and measure the in vivo effect. The sensitive balance of the sarcomeric proteins and muscle function has relevant implications in areas of gene doping in performance and therapy for neuromuscular disease., (Copyright © 2018 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: Acromegaly is a rare and underdiagnosed disorder caused, in more than 95% of cases, by a growth hormone (GH)-secreting pituitary adenoma. The GH hypersecretion leads to overproduction of insulin-like growth factor 1 (IGF-1) which results in a multisystem disease characterized by somatic overgrowth, multiple comorbidities, physical disfigurement, and increased mortality., Objective: This article aims to review the clinical features of acromegaly at diagnosis., Discussion/conclusion: Acromegaly affects both males and females equally and the average age at diagnosis ranges from 40 to 50 years (up to 5% of cases < the age 20). Due to insidious onset and slow progression, acromegaly is often diagnosed five to more than ten years after its onset. The typical coarsening of facial features include furrowing of fronthead, pronounced brow protrusion, enlargement of the nose and the ears, thickening of the lips, skin wrinkles and nasolabial folds, as well as mandibular prognathism that leads to dental malocclusion and increased interdental spacing. Excessive growth of hands and feet (predominantly due to soft tissue swelling) is present in the vast majority of acromegalic patients. Gigantism accounts for up to 5% of cases and occurs when the excess of GH becomes manifest in the young, before the epiphyseal fusion. The disease also has rheumatologic, cardiovascular, respiratory, neoplastic, neurological, and metabolic manifestations which negatively impact its prognosis and patients quality of life. Less than 15% of acromegalic patients actively seek medical attention for change in appearance or enlargement of the extremities. The presentation of acromegaly is more often related to its systemic comorbidities or to local tumor effects.

Objective. This prospective open trial aimed to evaluate the efficacy and safety of isotretinoin (13-cis-retinoic acid) in patients with Cushing's disease (CD). Methods. Sixteen patients with CD and persistent or recurrent hypercortisolism after transsphenoidal surgery were given isotretinoin orally for 6-12 months. The drug was started on 20 mg daily and the dosage was increased up to 80 mg daily if needed and tolerated. Clinical, biochemical, and hormonal parameters were evaluated at baseline and monthly for 6-12 months. Results. Of the 16 subjects, 4% (25%) persisted with normal urinary free cortisol (UFC) levels at the end of the study. UFC reductions of up to 52.1% were found in the rest. Only patients with UFC levels below 2.5-fold of the upper limit of normal achieved sustained UFC normalization. Improvements of clinical and biochemical parameters were also noted mostly in responsive patients. Typical isotretinoin side-effects were experienced by 7 patients (43.7%), though they were mild and mostly transient. We also observed that the combination of isotretinoin with cabergoline, in relatively low doses, may occasionally be more effective than either drug alone. Conclusions. Isotretinoin may be an effective and safe therapy for some CD patients, particularly those with mild hypercortisolism.

Successful discontinuation of cabergoline (CAB) treatment has been reported in 31-75% of prolactinomas patients treated for at least 2 years. In contrast, it is not well established whether CAB therapy can be successfully withdrawn after a failed first attempt. This prospective open trial was designed to address this topic and to try to identify possible predictor factors. Among 180 patients with prolactinomas on CAB therapy, the authors selected those who fulfilled very strict criteria, particularly additional CAB therapy for at least 2 years, normalization of serum prolactin (PRL) levels following CAB restart, no tumor remnant >10 mm, no previous pituitary radiotherapy or surgery; and current CAB dose ≤1.0 mg/week. Recurrence was defined as an increase of PRL levels above the upper limit of normal. A total of 34 patients (70.6% female) treated with CAB for 24-30 months were recruited. Ten patients (29.4%) remained without evidence of recurrence after 24-26 months of follow-up. Twenty-four patients (70.6%) recurred within 15 months (75% within 12 months) after drug withdrawal and ~80% were restarted CAB. Median time to recurrence was 10.5 months (range, 3-15). Despite overlapping values, non-recurring patients had significantly lower mean PRL levels before withdrawal. Moreover, the recurrence rate was lower in subjects without visible tumor on pituitary magnetic resonance imaging (MRI) than in those with small remnant tumor (60 vs. 79%), though the difference was not statistically significant (P = 0.20). No other characteristic could be identified as a predictor of successful CAB discontinuation. In conclusion, a second attempt of CAB withdrawal after two additional years of therapy may be successful, particularly in patients with lower PRL levels and no visible tumor on pituitary MRI. Close monitoring of PRL level is mandatory, especially within the first year after withdrawal, where most recurrences are detected.

Objective: The objectives of this study are to estimate the prevalence of arterial hypertension (AH) in an adult population with a predominance of families with low education and income levels, in the hinterlands of Pernambuco, Brazil, and to analyze its association with other factors related to cardiovascular diseases (CVD)., Methods: A cross-sectional study in 2008/2009 was conducted with a sample of 198 subjects stratified by age, and representative of the urban adult population of the Canaã district of city of Triunfo, in the hinterlands of Pernambuco, Brazil., Results: One hundred ninety eight individuals with average age of 57.7 years old (31 to 90 years-old), mainly women (65.6%), and with low income and education levels (81.3% with a monthly income of less than one minimum wage) were evaluated. Among these, 127 (64.1%) were identified as having AH, 54 (42.5%) of whom had no prior diagnosis. From those who were previously diagnosed, only 31.3% had good blood pressure control. Higher prevalence was observed in those individuals with lower incomes, higher body mass indexes (BMI), and those with metabolic syndrome (MS)., Conclusion: These data demonstrated that there was a high prevalence of AH in the urban, low education and income levels adult population of Triunfo, strongly associated with lower income levels, elevated BMI, and the presence of MS; and a high prevalence of bad blood pressure control among the previously diagnosed cases. These results indicate that more effective interventions for early detection and adequate control of this disease and its comorbidities are necessary.

Latin America faces unique challenges in the treatment of type 2 diabetes mellitus. The Asociación Latinoamericana de Diabetes (Latin American Diabetes Association, ALAD) brought together medical associations in 17 countries in Latin America to produce a consensus statement regarding the treatment of type 2 diabetes. The goal of the document is to provide practical recommendations that will guide clinicians through a simple decision-making process for managing patients. The cornerstone elements for therapeutic decision making are: severity of hyperglycemia, clinical condition of the patient (stable or with metabolic decompensation), and body mass index. The consensus includes a section devoted specifically to patients with obesity. Information is presented as highly-relevant clinical questions. The algorithm is based on the scientific recommendations of the 2006 ALAD guidelines (a document prepared using an evidence-based approach) and data from recent randomized controlled studies.

Background: Diabetes mellitus (DM) is a public health problem in Brazil. The objective of this study was to investigate the prevalence of DM and its relation with socio-demographic features and other cardiovascular risk factors in a adult population from the wilderness of Pernambuco, Brazil., Subjects and Methods: In 2008/2009 a cross-sectional study in the adult urban population of Canãa district, city of Triunfo, in the wilderness of Pernambuco/Brazil was conducted. A representative sample of 198 individuals, with average age of 57.7 years, 80% with primary education and 81.3% with a monthly income of less than 1 minimum wage was randomly selected., Results: A prevalence of diabetes of 13.6% and 7.6% of disglycemia (6.6% of impaired fasting glycemia, and 1.0% of impaired glucose tolerance) was found. Among those with diabetes, 24% had no prior diagnosis. Among diabetics, metabolic syndrome (MS) and arterial hypertension (AH) were diagnosed in 87.5% and 68%, respectively. Besides these, there was a positive and significant association between DM and BMI, and between DM and MS., Conclusion: These data demonstrate a high prevalence of DM in the adult urban population from the wilderness of Pernambuco/Brazil. These results as well as their association with obesity and MS, indicate that more effective interventions are necessary for the prevention of these diseases also outside principal urban centers.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

Objective: To discuss current aspects of use of antipsychotics considering their metabolic side effects profile, which includes weight gain, dyslipidemias, diabetes and metabolic syndrome. Such metabolic effects increase the risk of mortality by cardiovascular disease, which is the leading cause of death among schizophrenic patients., Method: A consensus meeting was held, with participation of endocrinologists and psychiatrists specialists in schizophrenia and, based on a literature review, an article was elaborated emphasizing practical and helpful recommendations to clinicians., Results and Conclusions: Monitoring metabolic side effects is essential to patients taking antipsychotics, particularly in the case of second generation antipsychotics. Efficacy and tolerability should be carefully balanced in all phases of treatment.

Cushing's syndrome (CS) during pregnancy is a rare condition with fewer than 150 cases reported in the literature. Adrenal adenomas were found to be the commonest cause, followed by Cushing's disease. The gestation dramatically affects the maternal hypothalamic-pituitary-adrenal axis, resulting in increased hepatic production of corticosteroid-binding globulin (CBG), increased levels of serum, salivary and urinary free cortisol, lack of suppression of cortisol levels after dexamethasone administration and placental production of CRH and ACTH. Moreover, a blunted response of ACTH and cortisol to exogenous CRH may also occur. Therefore, the diagnosis of CS during pregnancy is much more difficult. Misdiagnosis of CS is also common, as the syndrome may be easily confused with preeclampsia or gestational diabetes. Because CS during pregnancy is usually associated with severe maternal and fetal complications, its early diagnosis and treatment are critical. Surgery is the treatment of choice for CS in pregnancy, except perhaps in the late third trimester, with medical therapy being a second choice. There does not seem to be a rationale for supportive treatment alone.

Aim: The aim of this study was to evaluate the clinical and laboratory features of 64 patients with macroprolactinemia and to compare them to those of individuals with monomeric hyperprolactinemia., Methods: The study included 64 patients (54 women and 10 men) with macroprolactinemia and 96 patients (70 women and 26 men) with monomeric hyperprolactinemia (32 with prolactinomas)., Results: Symptoms related to prolactin (PRL) excess were found in about 44% of individuals from the macroprolactinemia group and in 88.5% of patients with monomeric hyperprolactinemia (P<0.0001). However, the frequency of menstrual disturbances (oligomenorrhea or amenorrhea), galactorrhea and erectile dysfunction did not differ in both groups. In contrast, the association of galactorrhea and menstrual disturbances was significantly more prevalent in women with monomeric hyperprolactinemia. Although mean PRL levels were higher in patients with monomeric hyperprolactinemia (565.9+/-2726.4 vs 113.3+/-94.5 ng/mL, P<0.001), there was a great overlap between both groups. Among macroprolactinemic patients, pituitary magnetic resonance imaging revealed an image suggestive of a microadenoma in 7 (10.9%) and a macroadenoma in 1 (1.6%). Normalization of PRL levels during therapy with dopamine agonists was significantly more frequent in patients with monomeric hyperprolactinemia than in subjects with macroprolactinemia (78.6% vs 32%, P=0.0006)., Conclusion: Our data show that symptoms related to PRL excess are frequently found in subjects with macroprolactinemia. Moreover, no clinical or laboratory features could reliably differentiate macroprolactinemic patients from those with monomeric hyperprolactinemia. Therefore, the screening for macroprolactin should not be restricted to asymptomatic patients.

We studied clinical and laboratorial features of 73 patients with endogenous Cushing's syndrome, subdivided as follows: 46 (63%) with Cushing's disease (CD), 21 (28.7%) with an adrenal tumor and 6 (8.2%) with ectopic ACTH secretion (EAS). The rate of typical manifestations of hypercortisolism was similar regardless its etiology. In 100% of cases of Cushing's syndrome we observed serum cortisol levels greater than 1.8 microg/dL in low-dose dexamethasone (DMS) suppression tests, as well as elevation of serum or salivary midnight cortisol. However, urinary free cortisol was normal in 11.5% of patients. ACTH levels were suppressed in patients with adrenal tumors, normal or high in CD and always high in EAS. In the 8-mg overnight DMS suppression test, serum cortisol suppression > 50% was observed in 78.2% of cases of CD and in 33.3% of subjects with EAS, while an 80% suppression was only seen in CD. After stimulation with CRH or DDAVP an ACTH increase > 35% occurred in 81% of individuals with CD and 16.6% of those with EAS, while an ACTH increase > 50 achieved 100% specificity. Moreover, the combination of serum cortisol suppression > 50% and an ACTH increase > 35% in both tests only occurred in Cushing's disease. Pituitary magnetic resonance imaging identified 100% of macroadenomas and 59.4% of microadenomas in patients with CD. Among 10 patients that underwent bilateral inferior petrosal sinus sampling, a central-to-peripheral ACTH gradient > 3 after CRH or DDAVP had 90% sensitivity and 100% specificity for Cushing's disease.

Type 2 Diabetes mellitus (DM2) is a complex, multifactorial and worldwide metabolic disease that affects quality and lifestyle of patients. Patients with diabetes can have a 15-year or more reduction of lifetime and the high mortality is due to cardiovascular (CV) complications. Effective strategies for the reduction of the impact of DM2 on CV disorders for the next years and attention concerning to strategies of prevention, mainly for the populations with larger risk of developing the disease, are essential. In that context, impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG) must suffer intervention strategies in order to minimize the risk for diabetes. Behavior modification (diet therapy and physical activity) must be stimulated, and pharmacological agents have to be used when indicated. Studies worldwide have been confirming the effectiveness of lifestyle strategies and even the use of pharmacological agents for the prevention of DM2.

A fifty-nine year old man, known to have hypertrophic cardiomyopathy, presented worsening of angina. Multivessel coronary artery disease was diagnosed, and he underwent myocardial revascularization (mammary and two safenous grafts were implanted) with good evolution and reduction of left atrium dimension.

Objective: To study the diagnosis, prognosis and management of spontaneous rupture of the esophagus., Design: This is a retrospective study through the analysis of two cases with delayed diagnosis and subsequent treatment at the Track Surgery Service. LOCALE: The study was performed at the Thoracic Surgery Unit of the Hospital do Servidor Público Estadual Francisco Morato de Oliveira in the city of São Paulo. This is a specialized service., Participants: The two patients reported on had suffered spontaneous rupture of the esophagus. They were transferred to the Thoracic Surgery Unit because of the worsening of their condition in the previous institution which they had been admitted into., Measurement: The two patients with esophagus pleural fistula received similar treatment, initially advocated by Kanashin in Russia and Hauer-Santos in the United States, which consists of washing the fistula and using continuous pleural aspiration., Results: Although both patients had to spend a long period of time in hospital, their evolution was satisfactory with the treatment adopted, and the fistula closed., Conclusion: The authors conclude that the method of lavage of the mediastinum and continuous pleural aspiration, in patients who after spontaneous rupture of the esophagus developed a pleural esophagus fistula due to belated diagnosis, is an alternative and satisfactory therapy. Furthermore, in order to have the best outcome, an early diagnosis is recommended and thoracostomy as the surgical procedure, with primary suture.

The objective of this study is to decode the etiopathogenesis, the clinical feature, the diagnosis and the prognosis of the acute mediastinitis resulting of infectious processes of the cephalic segment. Three out of five patients studied presented focus of dental origin and two patients presented focus in the face area. One of them presented Ludwig's Angina before the suppurative process would spread over the mediastinum. In the others, there was fast expansion through the fascial spaces of the neck and, in two of them, besides the mediastinum, there was pleuropericardial involvement. Three patients died due to respiratory insufficiency and two survived with complications. The mediastinitis after cervical suppuration is a special and extremely serious kind of endothoracic infection. The pus reaches that area through the fascial spaces of the neck, taking the organism to an alarming toxemic feature. The rarity of the disease, the little is known about its physiopathology and the initial care of the patient in non-specialized services, which are not familiarized with this type of feature, are factors that can delay the diagnosis and worsen the prognosis.

Prof. Lyra discusses in this article the basic problem of criminological sciences, stating that its essential object of study is the determination of the genesis of crime. The Author states that, before defining the crime genesis, it is necessary to outline, through a synthesis of epistemological restructurization of criminology itself. This way, we can develop a conception of Dialectic Criminology, where the term "dialectic" does not necessarily coincide with a marxist posture, but it extends along much more complex and comprehensive parameters. Dialectic Criminology is defined, in Lyra's conception, as a Classified Criminology, synthetizing both the psychological approach (clinical criminology, or micro-criminology), and the sociological approach (sociological criminology or macro-criminology), according to an anthropological basic frame of reference, which constitutes the new and original prerequisite. To this aim, according to Prof. Lyra, it is necessary to overcome merely biological or psychological theories, and the new sociologisms, which cannot explain deviant behavior without falling into dogmatism or relativism. It is necessary to give back to criminology its original ethico-philosophical roots, and to place the problem of crime within a new "praxis" concept, which takes into account the authentic freedom of man, interracting with historical evolution. This way, through Dialectic Criminology, we can overcome the conception of crime and delinquency viewed as counterparts of the concept of Law.