Hiperaldosteronismo primario: puntos de corte del cociente aldosterona/renina / Primary aldosteronism: Aldosterone/renin ratio cut-off points

Introducción: El hiperaldosteronismo primario (HAP) es la causa más frecuente de hipertensión endocrina, con una prevalencia del 6-12% en pacientes hipertensos. El cociente aldosterona/renina es el método de cribado de elección. Dada la variabilidad de sus puntos de corte, se sugiere contar con valores de referencia propios. Objetivos: 1) Optimizar los puntos de corte del cociente aldosterona/renina para el cribado de hiperaldosteronismo con la metodología actual; 2)evaluar la correlación y la sensibilidad diagnóstica de los cocientes aldosterona/actividad de renina plasmática (RAA) y aldosterona/concentración de renina (RAC) para el cribado de hiperaldosteronismo, y 3)determinar la prevalencia de hiperaldosteronismo en nuestra población. Materiales y métodos: Se determinaron los niveles de aldosterona (RIA competitivo en fase sólida RIAZENco Zentech), actividad de renina plasmática (RIA en fase sólida DiaSorin) y concentración de renina (quimioluminiscencia Liaison DiaSorin) en 345 sujetos (136 controles y 209 hipertensos). Se calcularon los cocientes RAA y RAC. Resultados: La prevalencia de HAP, tras confirmación diagnóstica, fue del 5,9% de los hipertensos. El valor de corte para sospecha de HAP determinado por curvas ROC fue 48,9(ng/dl)/(ng/ml/h) para RAA (sensibilidad 100% y especificidad 93,6%) y 2,3(ng/dl)/(μUI/ml) para RAC (sensibilidad 100% y especificidad 90,9%). Se observó buena correlación entre RAA y RAC (ρ=0,83; p<0,0001), con una concordancia diagnóstica presuntiva del 96,6%. Conclusiones: Hemos determinado en nuestra población nuevos valores de corte de RAA y RAC para el cribado de HAP, con buena sensibilidad y concordancia como métodos de cribado. Es importante contar con rangos de normalidad propios para evitar errores diagnósticos

Introduction: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, with a prevalence rate of 6-12% in hypertensive patients. Aldosterone/renin ratio (ARR) is the screening test of choice for PA. Because of the variable cut-off points of ARR, reference values related to the populations and methods considered are recommended. Objectives: (i)To optimize the ARR cut-off points for PA screening with current methods; (ii)to assess the correlation and diagnostic sensitivity of the plasma aldosterone concentration/plasma renin activity (ARR) ratio and the aldosterone concentration/renin concentration (ARC) ratios for PA screening, and (iii)to determine the prevalence of PA in our population. Materials and methods: Plasma aldosterone concentration and plasma renin activity levels were measured using radioimmunoassays (RIAZENco Zentech and RIA DiaSorin respectively), while a chemiluminescence assay (Liaison Diasorin) was used to test renin concentration. ARR and ARC ratios were calculated in 345 subjects (136 healthy subjects and 209 hypertensive patients). Results: Prevalence of PA was 5.9% after diagnostic confirmation. ROC curve analysis suggested an ARR threshold of 48.9(ng/dL)/(ng/mL/h) (100% sensitivity, 93.6% specificity) and an ARC threshold of 2.3(ng/dL)/(μIU/mL) (100% sensitivity, 90.9% specificity). Good correlation was seen between ARR and ARC (ρ=.83, P<.0001), with a presumptive diagnostic concordance of 96.6%. Conclusions: New cut-off values of ARR and ARC for screening of PA, with high sensitivity and good diagnostic concordance, were determined in the study population. It is important to have valid normal ranges to avoid diagnostic errors

Primary aldosteronism: Aldosterone/renin ratio cut-off points. / Hiperaldosteronismo primario: puntos de corte del cociente aldosterona/renina.

INTRODUCTION: Primary aldosteronism (PA) is the most common cause of endocrine hypertension, with a prevalence rate of 6-12% in hypertensive patients. Aldosterone/renin ratio (ARR) is the screening test of choice for PA. Because of the variable cut-off points of ARR, reference values related to the populations and methods considered are recommended. OBJECTIVES: (i)To optimize the ARR cut-off points for PA screening with current methods; (ii)to assess the correlation and diagnostic sensitivity of the plasma aldosterone concentration/plasma renin activity (ARR) ratio and the aldosterone concentration/renin concentration (ARC) ratios for PA screening, and (iii)to determine the prevalence of PA in our population. MATERIALS AND METHODS: Plasma aldosterone concentration and plasma renin activity levels were measured using radioimmunoassays (RIAZENco Zentech and RIA DiaSorin respectively), while a chemiluminescence assay (Liaison Diasorin) was used to test renin concentration. ARR and ARC ratios were calculated in 345 subjects (136 healthy subjects and 209 hypertensive patients). RESULTS: Prevalence of PA was 5.9% after diagnostic confirmation. ROC curve analysis suggested an ARR threshold of 48.9(ng/dL)/(ng/mL/h) (100% sensitivity, 93.6% specificity) and an ARC threshold of 2.3(ng/dL)/(µIU/mL) (100% sensitivity, 90.9% specificity). Good correlation was seen between ARR and ARC (ρ=.83, P<.0001), with a presumptive diagnostic concordance of 96.6%. CONCLUSIONS: New cut-off values of ARR and ARC for screening of PA, with high sensitivity and good diagnostic concordance, were determined in the study population. It is important to have valid normal ranges to avoid diagnostic errors.

Panhypopituitarism due to Wegener's granulomatosis.

Wegener's granulomatosis (WG) is a multi-system necrotizing granulomatous vasculitis which classically affects the upper respiratory tract, lungs and kidneys. Pituitary participation has been described in 24 patients in the literature to date. The aim of this article is to report a case of pituitary involvement in WG, and to present a literature review on this association. We present a female patient with WG who evolved with central diabetes insipidus (CDI), panhypopituitarism, and mild hyperprolactinemia. MRI showed an infiltrative pattern. Pituitary involvement has been reported in around 1% of patients with WG, mostly in women. It is represented by CDI and hypopituitarism. MRI generally shows pituitary enlargement, stalk thickening and loss of hyperintensity of the neurohypophysis. Permanent endocrine therapy is generally needed. WG should be considered in cases of CDI and hypopituitarism, essentially if a vasculitis is suspected and more common sellar disorders have been ruled out.

[Prevalence of depression and anxiety in a cohort of 761 obese patients: impact in adherence to therapy and its outcome]. / Prevalencia de depresión y ansiedad en una cohorte de 761 obesos: implicancias en la adherencia al tratamiento y sus resultados.

OBJECTIVE: To determine the prevalence of psychiatric disorders in 761 obese patients, prospectively assessing their impact in both adherence to therapy and its outcome. MATERIAL AND METHODS: Overweight and obesity were defined by body mass index (BMI), depression and anxiety according to "The Hospital Anxiety and Depressio Scale". Patients received a physical and biochemical evaluation, a hypochaloric diet and a training plan. Sibutramine was prescribed as anti-obesity drug. RESULTS: The mean age was 31,28 (SD 11,26) years. 74.77% were women. The mean weight was 91.36 kg with a BMI of 34,49 Kg/m2 (SD 6,29). The prevalence of possible, probable and definite anxiety/depression was: 56.3%/22.0%, 29.8%/6.2%, and 7.2%/0.8% respectively. Both initial and final weight and BMI were higher in definite and probable depression respectively, with a minor percentage of weight loss likewise. CONCLUSIONS: The studied psychiatric disturbances were prevalent in our population. Initial and final weight and BMI were higher in groups with more severe anxiety or depression. The percentage of weight loss and adherence to therapy were greater in groups of milder psychiatric disorders.

Panhypopituitarism due to Wegener's granulomatosis / Pan-hipopituitarismo causado pela granulomatose de Wegener

Wegener's granulomatosis (WG) is a multi-system necrotizing granulomatous vasculitis which classically affects the upper respiratory tract, lungs and kidneys. Pituitary participation has been described in 24 patients in the literature to date. The aim of this article is to report a case of pituitary involvement in WG, and to present a literature review on this association. We present a female patient with WG who evolved with central diabetes insipidus (CDI), panhypopituitarism, and mild hyperprolactinemia. MRI showed an infiltrative pattern. Pituitary involvement has been reported in around 1 percent of patients with WG, mostly in women. It is represented by CDI and hypopituitarism. MRI generally shows pituitary enlargement, stalk thickening and loss of hyperintensity of the neurohypophysis. Permanent endocrine therapy is generally needed. WG should be considered in cases of CDI and hypopituitarism, essentially if a vasculitis is suspected and more common sellar disorders have been ruled out.

A granulomatose de Wegener (GW) é uma vasculite necrotizante multissistêmica que afeta classicamente o trato respiratório superior, pulmões e rins. O envolvimento da hipófise foi descrita em 24 pacientes na literatura, até hoje. O objetivo deste artigo é relatar um caso de GW com envolvimento pituitário, e apresentar uma revisão da literatura sobre esta associação. Apresentamos uma paciente com GW que evoluiu para diabetes insipidus central (DIC), panhipopituitarismo e leve hiperprolactinemia. A RM mostrou um padrão infiltrativo. O envolvimento da hipófise foi relatado em cerca de 1 por cento dos pacientes cm GW, na sua maioria mulheres. A desordem é representada por DIC e hipopituitarismo. A RM geralmente mostra o aumento da hipófise, aumento da espessura da haste, e perda da hiperintensidade da neurohipofise. Normalmente, é necessária terapia endócrina permanente. A GW é geralmente considerada nos casos de DIC e hipopituitarismo, essencialmente se há suspeita de vasculite e quando desordens selares mais comuns foram descartadas.

Endocrine therapies and QTc prolongation.

QT interval represents the period between the initiation of depolarization and the end of repolarization of the ventricular myocardium. Excessive prolongation of this interval may drive to a potentially fatal ventricular tachyarrhythmia known as "torsades de pointes". Agents used to manage many endocrine disorders have been linked with QTc alterations. Among them, oral antidiabetic agents, lipid lowering and anti-obesity drugs, somatostatin analogues, thyroid and anti-thyroid agents, and adrenal steroids should be considered. Nevertheless, it is very well known that some endocrine diseases are associated with constraints in the repolarization reserve, and, as a consequence, with QTc prolongation. Besides, some disturbances in the clearance of certain drugs are more frequent in patients affected by selected endocrine entities. Taking these into account, the purpose of this article is to review the behavior of the most widely used drugs in endocrinology with regards to their potential QTc prolongation effect in human beings.

New treatments for type 2 diabetes mellitus: combined therapy with sitagliptin.

BACKGROUND: Sitagliptin is a highly selective oral dipeptidyl peptidase-4 inhibitor. This drug increases the plasma concentration of active glucagon like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide. These two hormones then simulate the secretion of insulin in a glucose-dependent manner and inhibit glucagon secretion, thus reducing circulating glucose levels. In animal models, GLP-1 increases beta-cell mass. OBJECTIVE: To review the efficacy and safety of sitagliptin in combined therapies (as add on or initial combination treatment) in type 2 diabetes. METHODS: A Medline search on published clinical trials involving sitagliptin in combined therapies was performed; additional information from published papers and abstracts to congresses on preclinical and basic science issues was also included to support the mechanistic rationale of combinations. RESULTS/CONCLUSION: In humans sitagliptin administration reduces fasting and postprandial glucose and A1c levels. Sitagliptin is as effective as glipizide (close to 0.7% mean A1c reduction), but has fewer hypoglycemic events than other oral insulin secretagogues. Since metformin reduces hepatic glucose production and increases GLP-1 release, combined therapy with sitagliptin becomes complementary and has been shown to have important additive effects. Sitagliptin combined with pioglitazone resulted in improved metabolic control when compared with pioglitazone plus placebo. Combined administration with insulin requires further studies. The weight neutral effect of sitagliptin, its glucose-dependent action (lower risk of hypoglycemia), the beneficial effects on beta-cell function and its eventual protective action on beta-cell mass makes it an excellent option for monotherapy or combined with metformin, glitazones or even sulfonylurea.

Non-invasive routes for insulin administration: current state and perspectives.

Diabetes mellitus is a chronic disease that usually requires multiple insulin injections to achieve adequate glycaemic control. This represents a major cause of reduced compliance to treatment. Consequently, other routes for insulin administration have been explored. During recent years, much progress in the development of inhaled insulin has been made. Inhaled insulin has shown favourable properties, such as a rapid onset of action, improved bioavailability and good tolerability; thereby providing satisfaction and ease of administration. However, long-term safety of inhaled insulin needs to be assessed, and the cost would be higher than injectable insulin. Nasal, oral and transdermal insulins are undergoing early phases of pharmacological development. The purpose of this review is to describe the latest developments in the area of non-invasive routes for insulin delivery.

Investigational treatments for Type 2 diabetes mellitus: exenatide and liraglutide.

Although a number of compounds are currently used to treat Type 2 diabetes mellitus, achieving a sustained glycaemic control over time is often not possible using oral antidiabetics. Endogenous incretins exhibit beneficial effects that could be useful for Type 2 diabetes mellitus treatment, such as stimulating insulin secretion during hyperglycaemia, improving beta-cell mass and function, reducing glucagon secretion, delaying gastric emptying, reducing postprandial hyperglycaemia and diminishing body weight; however, their short half-life makes them unsuitable for treatment. Incretin mimetics such as liraglutide and exenatide were developed to overcome this limitation. This review discusses the effects of these compounds and their potential as a new class of antidiabetic agents.

Abciximab does not inhibit the increase of thrombin generation produced in platelet-rich plasma in vitro by sodium arachidonate or tissue factor.

Aspirin and platelet membrane glycoprotein (GP) IIb/IIIa blockers are currently used for acute coronary events, and in percutaneous coronary intervention for preventing further coronary outcomes, because they inhibit platelet function. Aspirin also inhibits thrombin generation (TG) in platelet-rich plasma (PRP) activated by sodium arachidonate (AA). The effect of the platelet membrane GP IIb-IIIa (integrin alpha(IIb)beta(3)) blocker abciximab on thrombin generation was studied in vitro using PRP. Thirty healthy volunteers taking no medication, and 28 volunteers who had taken aspirin (160 mg/day for 3-4 days), were included in the protocol. Control or in vivo aspirinated PRP, stimulated or not by AA or tissue factor (TF), was investigated for the inhibitory effect of abciximab pre-incubated for 3 minutes. AA and TF added in vitro activated non-aspirinated PRP: lag-time (LT) and time to peak (TTP) were significantly shortened. Peak TG (PTG) and endogenous thrombin potential (ETG) were increased by AA but not TF; thus, AA seems to be more efficient than TF for TG in this system. Abciximab added in vitro to non-activated, non-aspirinated PRP had no effect on LT, TTP, or ETP, but caused a decrease in PTG that was not statistically significant. Abciximab (3 or 4 microg/mL) added in vitro to AA or TF-activated, non-aspirinated PRP produced no effect on TG, although in aspirinated platelets both LT and time to peak were prolonged. AA as well as TF added in vitro to PRP or in vivo aspirinated PRP increased TG, although AA seems to be more efficient in our assay system. Abciximab, which affects non-aspirinated, nonactivated PRP weakly, has no effect on AA or TF in activated control PRP or in vivo aspirinated PRP.

Insulin analogue therapy in pregnancies complicated by diabetes mellitus.

Pregnancies complicated by diabetes mellitus (DM) include pregestational DM and gestational DM, defined as carbohydrate intolerance of variable severity first detected during pregnancy. DM leads to poor pregnancy outcome. The aim of treatment is to control maternal hyperglycaemia and to imitate postprandial insulin release. Rapid-acting insulin analogues are suitable therapeutic candidates, as they are able to reduce postprandial hyperglycaemia (predictive of adverse pregnancy outcome). There is no excess risk of adverse fetal or maternal outcomes when compared with regular insulin. Data suggest that rapid-acting insulin analogues do not transfer to human placenta. Because of the reduced risk of hypoglycaemia and improved postprandial and overall glucose control, insulin analogues could be considered the rapid-acting insulin choice during pregnancy.