Aumento de la lipocalina orosomucoide-1 (ORM1) en sujetos con hiperaldosteronismo primario / Increase of lipocalin ORM1 in primary aldosteronism

El hiperaldosteronismo primario (HAP) es la causa más común de hipertensión arterial secundaria. A pesar de la prevalencia del HAP (6-10%) y sus consecuencias, los mecanismos que median los efectos deletéreos renales y extrarenales originados por la aldosterona más allá de la hipertensión arterial (ej. inflamación renal, alteraciones cardiacas y disfunción vascular), siguen siendo poco conocidos. Estudios previos sugieren que el exceso de aldosterona aumentaría proteínas sensibles a la activación del receptor de mineralocorticoides (MR), como las lipocalinas LCN2 (NGAL) y ORM1. OBJETIVO: Determinar la concentración de las lipocalinas ORM1, NGAL y NGAL-MMP9 en sujetos HAP. SUJETOS Y MÉTODOS: Estudio de cohorte transversal en sujetos adultos (similares en sexo, edad e IMC) separados en controles normotensos (CTL), hipertensos esenciales (HE) y con screening positivo de HAP (aldosterona ≥9 ng/dL y ARP < 1 ng/mL*h acorde a las guías internacionales de HAP). Se determinó la presión arterial sistólica (PAS) y diastólica (PAD), aldosterona plasmática, actividad renina plasmática (ARP) y la relación aldosterona / actividad de renina plasmática (ARR). Se determinó la concentración de NGAL, NGAL-MMP9 y ORM1 en suero por ELISA. RESULTADOS: Detectamos mayores niveles de ORM1 en sujetos HAP. No se detectaron diferencias en NGAL ni NGAL-MMP9 entre los grupos. Detectamos una asociación positiva de ORM1 con ARP (rho= -0,407, p=0,012) y con ARR (rho= 0,380 p= 0,021). CONCLUSIÓN: La mayor concentración de ORM1 en sujetos HAP y las asociaciones de ORM1 con aldosterona, ARP y ARR, proponen a esta proteína como un potencial biomarcador de HAP y de utilidad en el desarrollo de algoritmos diagnósticos de HAP.

Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension. Despite the prevalence of PA (6-10%) and its consequences, the mechanisms that mediate the deleterious renal and extrarenal effects caused by aldosterone beyond arterial hypertension (eg renal inflammation, cardiac alterations and vascular dysfunction), remain barely known. Previous studies suggest that excess aldosterone would increase proteins sensitive to activation of the mineralocorticoid receptor (MR), such as lipocalins LCN2 (NGAL) and ORM1. AIM: To determine the concentration of the lipocalins ORM1, NGAL and NGAL-MMP9 in PA subjects. SUBJECTS AND METHODS: Cross-sectional study in adult subjects (similar in sex, age and BMI) grouped as normotensive controls (CTL), essential hypertensive (HE) and subjects with positive PA screening (aldosterone ≥ 9 ng/dL and PRA <1 ng/mL*h, according to international PA guidelines). Systolic (SBP) and diastolic (DBP) blood pressure, plasma aldosterone, plasma renin activity (PRA), and plasma aldosterone renin ratio (ARR) were determined. The concentration of NGAL, NGAL-MMP9 and ORM1 in serum was determined by ELISA. RESULTS: We detected higher levels Recibido: 03-09-2021 of ORM1 in PA subjects. No differences in NGAL or NGAL-MMP9 were detected between the groups. We detected a positive association of ORM1 with ARP (rho = -0.407, p < 0.05) and with ARR (rho = 0.380 p <0.05). CONCLUSION: The high levels of ORM1 in PA subjects and the associations of ORM1 with aldosterone, ARP and ARR, suggest ORM1 is a potential biomarker of PA, and useful in the development of a diagnostic algorithm for PA.

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.(AU)

Hiperaldosteronismo primario en una población de pacientes hipertensos / Primary hyperaldosteronism in a population of hypertensive patients

El diagnóstico de hiperaldosteronismo primario (HPAP) aumentó en los últimos años y algunos autores lo consideran la principal causa de hipertensión arterial secundaria. Estudiamos la prevalencia de HPAP en el total de pacientes hipertensos atendidos en la Unidad de Hipertensión Arterial, en el período comprendido entre julio 1999 a julio 2017. Se incluyeron 2500 pacientes y en 79 se diagnosticó HPAP (3.2%). El HPAP fue más frecuente en mujeres (55.7%), observándose un incremento en la edad geriátrica con relación a estudios previos (27.8%). El diagnóstico se sospechó ante la presencia de kaliuria inapropiada y alcalosis metabólica, acompañada de un cociente aldosterona/actividad de renina plasmática superior a 30 (ng/dl)/(ng/ ml/h). Tras su confirmación se realizaron estudios de imagen para determinar la etiología. Se detectaron así 29 casos (36.8%) de adenomas productores de aldosterona y 5 de hiperplasia bilateral suprarrenal con nódulos. La tomografía computarizada identificó el 100% de los adenomas y de las hiperplasias con nódulos corticales bilaterales. El tratamiento con suprarrenalectomía y/o antialdosterónicos resultó eficaz en el control de la presión arterial en el 69.9% de los casos. Se comentan aspectos particulares de esta serie, como la remisión de la insuficiencia renal, la elevada presencia de litiasis urinaria hipercalciúrica y la detección de un carcinoma de mama tras dosis prolongadas de espironolactona.

The diagnosis of primary hyperaldosteronism (PHPA) has progressively increased over the last years and some authors consider it as the main cause of secondary hypertension. We studied the prevalence of PHPA in hypertensive patients followed at the Hypertension Unit from July 1999 to July 2017. A total of 2500 patients were included and diagnosis of PHPA was done in 79 of them (3.2%). It was more frequent in women (55.7%) with an increased incidence in the elderly, as compared to previous studies (27.8%). Initial diagnosis was suspected upon the presence of inappropriate kaliuria and metabolic alkalosis, associated to an aldosterone/plasma renin activity ratio > 30 (ng/dl)/(ng/ml/h). After confirmation of the presence of PA, imaging techniques to determine the etiology were performed. In this way, 29 cases (36.8%) of aldosterone-producing adenoma and 5 cases of bilateral adrenal hyperplasia with nodules were identified. Computed tomography identified the adenomas and hyperplasias with bilateral cortical nodules in all patients. Adrenalectomy and/o r antialdosteronics were efficient in controlling blood pressure in 69.9% of cases. Of note in this series was the remission of stage 3 chronic renal failure in two cases, the high prevalence of hypercalciuric urinary lithiasis and a case of breast carcinoma after prolonged treatment with spironolactone.

Actualización en el manejo clínico de la hipertensión hiporreninémica / Update in the clinical management of low renin hypertension

The renin-angiotensin-aldosterone system modulates volume, sodium and potassium homeostasis. In the setting of a high sodium diet, up to 30% of patients with hypertension have a low or suppressed renin and increased volume. This phenotype of low renin hypertension (LRH) is multifactorial and includes infrequent inherited genetic syndromes, milder phenotypes of classic diseases and environmental exposures. All these conditions have in common a higher cardiovascular risk mediated by the over activation of the mineralocorticoid receptor (MR), present not only in the kidney, but also in vasculature, myocardium and adipocytes. Consequently, the aim of LRH treatment goes beyond the control of blood pressure and requires antagonizing MR with specific pharmacologic agents, pursuing normalization of renin as a clinical objective. Due to the unusual evaluation of renin status by non-endocrinologists and lack of disease awareness, only a minority of hypertensive patients receive this pathophysiologically-driven treatment that should reduce cardiovascular outcomes.

Rabdomiólisis por hipopotasemia severa en paciente con síndrome de Conn / Rhabdomyolysis and profound hypokalemia in a patient with Conn´s syndrome

El Síndrome de Conn o hiperaldosteronismo primario se caracteriza por hipertensión, hipopotasemia con alcalosis metabólica y una masa adrenal. La rabdomiólisis puede ser secundaria a traumatismos, excesiva actividad muscular, enfermedades musculares hereditarias y otras causas médicas, como la hipopotasemia. Presentamos el caso de un hombre de 46 años con rabdomiólisis secundaria e hipopotasemia severa como expresión de hiperaldosteronismo primario por un adenoma suprarrenal(AU)

Conn's syndrome or primary hyperaldosteronism is characterized by hypertension, hypokalemia with metabolic alkalosis and the presence of an adrenal mass. Rhabdomyolysis can be secon- dary to trauma, excessive muscle activity, hereditary muscle diseases and other medical causas, such as hypokalemia. We present the case of a 46-year-old man with secondary rhabdomyolisis and hypokalemia as an-expresión of primary hyperaldosteronism due to an adrenal adenoma(AU)

¿Como optimizar el diagnóstico funcional de los incidentalomas suprrarenales? Importancia de un estudio protocolizado / How to optimize the functional diagnosis of suprarenal incidenta- lomas? Importance of a protocolized study

Adrenal incidentalomas are an increasingly common pathology. Although historically they have been considered largely non-functioning, recent evidence suggests that the usually performed study is incomplete and/or not sensitive enough. In the last decade the clinical spectrum of adrenal hypercortisolism has expanded considerably, including milder cases which are also associated with cardiovascular morbidity and even mortality. Furthermore, primary aldosteronism has also expanded beyond the classic phenotype with advanced vascular damage, resistant hypertension and hypokalemia, currently including asymptomatic, normotensive and normokalemic patients. For this reason, a correct protocolized study is essential in all adrenal incidentalomas, including a precise radiological characterization, as well as a systematic hormonal evaluation using more sensitive cut points. The findings of this workup are relevant, because they allow a more individualized approach to the medical and surgical management of these patients.

Los incidentalomas suprarrenales son una patología cada vez más frecuente. Si bien históricamente han sido considerados no funcionantes en su gran mayoría, evidencia reciente sugiere que el estudio habitual es incompleto y/o poco sensible. En la última década el espectro clínico del hipercortisolismo de origen adrenal se ha ampliado de forma considerable, incluyendo casos leves que también se asocian a morbilidad cardiovascular e incluso mortalidad. Por otro lado, el hiperaldosteronismo primario también ha expandido su fenotipo más allá del clásicamente descrito con daño vascular avanzado, hipertensión resistente e hipokalemia, abarcando en la actualidad a pacientes asintomáticos, normotensos y normokalemicos. Por esta razón es imprescindible un correcto estudio protocolizado en todo incidentaloma suprarrenal, incluyendo una precisa caracterización radiológica, así como una evaluación hormonal sistemática utilizando puntos de corte más sensibles. Los hallazgos de este estudio son relevantes, pues permiten guiar de forma más individualizada el manejo médico y quirúrgico de estos pacientes.

Diagnosis and management of primary aldosteronism

ABSTRACT Primary aldosteronism (PA) is the most common form of secondary hypertension (HTN), with an estimated prevalence of 4% of hypertensive patients in primary care and around 10% of referred patients. Patients with PA have higher cardiovascular morbidity and mortality than age- and sex-matched patients with essential HTN and the same degree of blood pressure elevation. PA is characterized by an autonomous aldosterone production causing sodium retention, plasma renin supression, HTN, cardiovascular damage, and increased potassium excretion, leading to variable degrees of hypokalemia. Aldosterone-producing adenomas (APAs) account for around 40% and idiopathic hyperaldosteronism for around 60% of PA cases. The aldosterone-to-renin ratio is the most sensitive screening test for PA. There are several confirmatory tests and the current literature does not identify a "gold standard" confirmatory test for PA. In our institution, we recommend starting case confirmation with the furosemide test. After case confirmation, all patients with PA should undergo adrenal CT as the initial study in subtype testing to exclude adrenocortical carcinoma. Bilateral adrenal vein sampling (AVS) is the gold standard method to define the PA subtype, but it is not indicated in all cases. An experienced radiologist must perform AVS. Unilateral laparoscopic adrenalectomy is the preferential treatment for patients with APAs, and bilateral hyperplasia should be treated with mineralocorticoid antagonist (spironolactone or eplerenone). Cardiovascular morbidity caused by aldosterone excess can be decreased by either unilateral adrenalectomy or mineralocorticoid antagonist. In this review, we address the most relevant issues regarding PA screening, case confirmation, subtype classification, and treatment.

Long-term Results after CT-Guided Percutaneous Ethanol Ablation for the Treatment of Hyperfunctioning Adrenal Disorders

OBJECTIVES: To evaluate the safety and long-term efficacy of computed tomography-guided percutaneous ethanol ablation for benign primary and secondary hyperfunctioning adrenal disorders. METHOD: We retrospectively evaluated the long-term results of nine patients treated with computed tomography-guided percutaneous ethanol ablation: eight subjects who presented with primary adrenal disorders, such as pheochromocytoma, primary macronodular adrenal hyperplasia and aldosterone-producing adenoma, and one subject with Cushing disease refractory to conventional treatment. Eleven sessions were performed for the nine patients. The patient data were reviewed for the clinical outcome and procedure-related complications over ten years. RESULTS: Patients with aldosterone-producing adenoma had clinical improvement: symptoms recurred in one case 96 months after ethanol ablation, and the other patient was still in remission 110 months later. All patients with pheochromocytoma had clinical improvement but were eventually submitted to surgery for complete remission. No significant clinical improvement was seen in patients with hypercortisolism due to primary macronodular adrenal hyperplasia or Cushing disease. Major complications were seen in five of the eleven procedures and included cardiovascular instability and myocardial infarction. Minor complications attributed to sedation were seen in two patients. CONCLUSION: Computed tomography-guided ethanol ablation does not appear to be suitable for the long-term treatment of hyperfunctioning adrenal disorders and is not without risks.

Pseudohipoaldosteronismo y aparente exceso de mineralocorticoides: cara y ceca en dos pacientes pediátricos / Pseudohypoaldosteronism and apparent mineralocorticoid excess: two faces, two pediatric patients

Los síndromes endocrinológicos con hipofunción o hiperfunción con niveles paradójicos de dosajes hormonales han sido bien caracterizados en los últimos años del siglo XX, a partir del desarrollo de técnicas genéticas y moleculares. Presentamos dos pacientes con pseudohipoaldosteronismo y aparente exceso de mineralocorticoides como síndromes en espejo, con la intención de alertar al médico clínico respecto de su consideración como entidad diagnóstica en niños con alteraciones hidroelectrolíticas. (AU)

Endocrinological syndromes with underactive or overactive hormonal levels with paradoxical dosages have been well characterized over the years of the twentieth century, from the development of genetic and molecular techniques. We present two patients with pseudohypoaldosteronism and apparent mineralocorticoid excess as mirror syndromes, with the aim to alert the clinician regarding their consideration as a diagnostic entity in children with fluid and electrolyte disturbances. (AU)

Aldosterona e IL-17 en la génesis de la hipertensión arterial mineralocorticoídea, un estudio ex vivo / Aldosterone and il-17 in the genesis of mineralocorticoid arterial hypertension: an ex vivo study

Background: Treatment of dendritic cells (DC) with aldosterone induces the secretion of IL-6 and TGF-beta. The polarization of naïve T cells to helper 17 T lymphocytes with DCs pre-incubated with aldosterone, has been described in vivo, generating an IL-17 hyper-secreting phenotype, a cytokine associated with cardiac and renal fibrosis. There are mineralocorticoid receptors (MR) in immune cells and their activation may determine the inflammatory (M1) or adaptive (M2) macrophage phenotype. Aldosterone levels could regulate immunogenic gene expression in these cells, modulating the liberation of specific cytokines. Aim: To assess in humans the association of aldosterone levels and IL-17 with inflammatory markers in peripheral blood mononuclear cells (PBMC). Material and Methods: In blood samples of 176 participants aged 18 to 67 years (61 percent women) with a body mass index of 27.1 +/- 4.8 kg/m2, aldosterone, plasma renin activity (ARP), cortisol, C reactive protein, andIL-17 were measured. mRNA was isolated from PBMCs to measure the expression of MR RAC-1, HO-1, TLR-4, CD-14, NGAL and IL-17 by real time polymerase chain reaction. Results: Aldosterone correlated positively with ARP and the expression of CD-14 in PBMCs. Plasma levels of IL-17 were positively associated with the expression of MR, Rac1a and NGAL. Conclusions: Aldosterone and IL-17 levels were associated with inflammatory activation markers in PBMC, which could activate MRand promote a subclinical inflammatory status inducing hypertension.

Hiperaldosteronismo primario y otras formas de hipertensión arterial endocrina / Primary hyperaldosteronism and other forms of endocrine arterial hypertension

La hipertensión arterial (HTA) dependiente de mineralocorticoides representa actualmente una de las formas secundarias de hipertensión de mayor prevalencia. Entre las causas más prevalentes está el hiperaldosteronismo primario (HAP) cuya prevalencia es cercana al 10 por ciento de la población de hipertensos. El HAP se detecta principalmente por una elevación de la razón aldosterona a actividad renina plasmática (ARR), ya que la hipokalemia es infrecuente de encontrar. La fisiopatología del HAP se presenta como un desequilibrio en el control electrolítico a nivel renal, por mayor actividad del receptor mineralocorticoides (MR), lo cual aumenta el volumen intravascular y la presión arterial. Recientemente se ha demostrado también que el exceso de aldosterona afecta también el endotelio vascular, el tejido cardiaco entre otros. Este exceso puede ser por una alteración a nivel de la glándula suprarrenal (generalmente hiperplasia o adenoma) o formas genéticas (familiares). Por otra parte, alteraciones parciales o totales de la enzima 11ß-Hidroxiesteroide deshidrogenasa tipo 2 (11ß-HSD2) resulta en una metabolización total o parcial de cortisol, imitando los efectos de aldosterona sobre MR. La actividad de esta enzima se evalúa midiendo la razón cortisol a cortisona en suero por HPLC-MS/MS. La prevalencia de alteraciones parciales de la actividad de la enzima 11ß-HSD2 en estudios de cohorte alcanza en alrededor del 15 por ciento en población hipertensa. El diagnóstico del HAP o deficiencias de 11BHSD2, permitiría un tratamiento específico del cuadro hipertensivo mediantes el uso de bloqueadores del receptor mineralocorticoideo y/o uso de corticoides de acción prolongada sin actividad mineralocorticoidea como dexametasona o betametasona.(AU)

Mineralocorticoid arterial Hypertension represents currently one of the secondary forms of hypertension most prevalent. Among the most prevalent causes is the primary aldosteronism (PA) whose prevalence is close to 10 percect of the hypertensive population. PA is detected by elevated aldosterone to plasma renin activity ratio (ARR) and the hypokalemia is rare to find. The pathophysiology of PA is presented as a renal electrolyte imbalance, increasing mineralocorticoid receptor (MR) activity, intravascular volume and blood pressure. Recently it has also shown that excessive aldosterone also affects vascular endothelium, heart tissue among others. This excess can be associated to an adrenal gland (usually hyperplasia or adenoma) or genetic (familiar) alteration. Similarly, partial or total impairment in 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) enzyme affects the cortisol metabolism, mimicking the effects of aldosterone on MR. The activity of this enzyme is evaluated by measuring the serum cortisol to cortisone ratio by HPLC-MS/MS. The prevalence of partial alterations of the activity of 11ß-HSD2 enzyme in cohort studies reached at around 15 percent in hypertensive population. The diagnosis of PA or an impairment in 11ß-HSD2 activity allows specific treatments of hypertensive patients using mineralocorticoid receptor blockers and/or use of long-acting corticosteroids without mineralocorticoid activity as dexamethasone or betamethasone.(AU)

Hiperaldosteronismo primário, como descrito por Conn. Relato decaso / Hyperaldosteronism, as described by Conn. Case report

O hiperaldosteronismo primário é causa de hipertensão arterialsecundária, com possibilidade de cura após cirurgia em 30a 75% dos casos. O objetivo deste estudo foi relatar um casode hipertensão arterial secundária a adenoma adrenal produtorde aldosterona. Paciente feminino, 35 anos, natural de Beruri(AM), procedente de Manaus, foi admitida com pressão arterialde 220x125mmHg associada a fraqueza muscular de membrosinferiores e câimbras. Na história patológica pregressa, havia orelato de hipertensão arterial diagnosticada há 2 anos, em tratamentocom três classes de anti-hipertensivos. Durante internaçãoem hospital geral, o quadro relatado associado à hipocalemiae alcalose metabólica sugeriram diagnóstico de hipertensão arterialsecundária a hiperaldosteronismo primário. Níveis elevadosde aldosterona plasmática, com renina suprimida e relação aldosterona-renina elevada, confirmaram o diagnóstico de hiperaldosteronismoprimário. A tomografia computadorizada deabdome evidenciou lesão tumoral com 2,3x2,0cm em glândulasuprarrenal esquerda sugestiva de adenoma adrenal. Pacientefoi submetida a adrenalectomia à esquerda com histopatologiacompatível com adenoma adrenal. Seis meses após a cirurgia,paciente evoluiu com normalização da calemia, porém mantevehipertensão arterial com necessidade de terapia anti-hipertensiva,sem novos picos hipertensivos. Se hiperaldosteronismo primáriodiagnosticado precocemente, há possibilidade de cura dahipertensão arterial secundária após adrenalectomia, reduzindo o efeito deletério da mesma sobre os sistemas cardiovascular, cerebrovasculare renal.(AU)

The primary hyperaldosteronism is a cause of secondaryhypertension, with the possibility of healing after surgery in 30to 75% of cases. The objective of this study was to report a caseof secondary hypertension to aldosterone-producing adrenaladenoma. A female patient, 35 years, from Beruri (AM), Brazil,who came to Manaus, was admitted into the emergency room withblood pressure of 220x125mmHg, associated with lower limbmuscle weakness and cramps. In the past medical history, there wasa report of hypertension diagnosed 2 years before, and she was undertreatment with three classes of antihypertensive drugs. Duringhospitalization in a general hospital, the case reported associatedto hypokalemia and metabolic alkalosis suggested a diagnosis ofhypertension secondary to primary hyperaldosteronism. Elevatedlevels of plasmatic aldosterone, suppressed renin and highaldosterone-renin relation suggested primary hyperaldosteronism.The abdominal computerized tomography scan revealed a tumor of2.3x2.0cm in the left adrenal gland, suggesting adrenal adenoma.Patient underwent left adrenalectomy and histopathology wascompatible to adrenal adenoma. After 6 months of surgery, thepatient experienced normalization of kalemia but kept arterialhypertension, requiring anti-hypertensive therapy, but had no othershypertensive peaks. Early diagnosis of primary hyperaldosteronismallowed the cure of hypertension after adrenalectomy, reducingdeleterious effects of high blood pressure levels on the cardiovascular,cerebrovascular and renal systems.(AU)

Screening for primary aldosteronism in an argentinian population: a multicenter prospective study

Objectives Primary aldosteronism (PA) is characterized by the autonomous overproduction of aldosterone. Its prevalence has increased since the use of the aldosterone (ALD)/plasma renin activity (PRA) ratio (ARR). The objective of this study is to determine ARR and ARC (ALD/plasma renin concentration ratio) cut-off values (COV) and their diagnostic concordance (DC%) in the screening for PA in an Argentinian population.Design multicenter prospective study.Subjects and methods We studied 353 subjects (104 controls and 249 hypertensive patients). Serum aldosterone, PRA and ARR were determined. In 220 randomly selected subjects, 160 hypertensive patients and 60 controls, plasma renin concentration (PRC) was simultaneously measured and ARC was determined.Results According to the 95th percentile of controls, we determined a COV of 36 for ARR and 2.39 for ARC, with ALD ≥ 15 ng/dL. In 31/249 hypertensive patients, ARR was ≥ 36. PA diagnosis was established in 8/31 patients (23/31 patients did not complete confirmatory tests). DC% between ARR and ARC was calculated. A significant correlation between ARR and ARC (r = 0.742; p < 0.0001) was found only with PRA > 0.3 ng/mL/h and PRC > 5 pg/mL. DC% for ARR and ARC above or below 36 and 2.39 was 79.1%, respectively.Conclusion This first Argentinian multicenter study determined a COV of 36 for ARR and 2.39 for ARC. Applying an ARR ≥ 36 in the hypertensive group, we confirmed PA in a higher percentage of patients than the previously reported one in our population. As for ARC, further studies are needed for its clinical application, since DC% is acceptable only for medium range renin values.

Body mass index as a determinant for metabolic-related changes in resistant hypertension / Índice de massa corporal como fator determinante de alterações metabólicas na hipertensão arterial

BACKGROUND AND OBJECTIVE: Obesity is a common feature of resistant arterial hypertension (RHTN) and it is considered a strong risk factor for the lack of blood pressure control. Moreover, increased aldosterone levels have been associated with impaired glucose metabolism and may interact with adipose tissue deregulating inflammatory adipokines such as leptin. This study aimed to verify the influence of obesity in aldosterone and leptin plasma levels as well as in markers ofglucose metabolism in RHTN subjects. METHODS: Ninetyone resistant hypertensive patients were divided into two subgroups by the mean body mass index (BMI): (i) a more obese (OBS, N=41, BMI>31.5kg/m2) and (ii) a leaner group (LNR,N=50, BMI<31.5kg/m2). We determined body composition by bioimpedance (BIA 450). Fasting glucose, glycated hemoglobin (HbA1c) as well as aldosterone (radioimmunoassay) and leptin (enzyme immunoassay) levels were also evaluated. RESULTS: OBS subgroup showed altered glucose metabolism by fasting glucose (129±48 vs. 107±32mg/dL, p=0.04) and glycated hemoglobin (7.6±2.3 vs. 6.8±1.9%, p=0.03). Plasma aldosterone (137.9±102.0 vs. 92.6±67.9pg/ml, p=0.03) as well as leptin levels (24.4±17.2 vs. 36.4±23.5ng/ml, p=0.01) were also higher in OBS compared with LNR group. Multiple linear regression indicated that glucose level is independently associated with obesity in RHTN patients. CONCLUSIONS: Our findings demonstrated that a greater body mass index may be determinantfor deregulating glucose metabolism as well as aldosterone and leptin levels in resistant hypertensive subjects.

JUSTIFICATIVA E OBJETIVO: A obesidade é uma característica comum da hipertensão arterial resistente (HAR) e é considerado um forte fator de risco para a falta de controle da pressão arterial. Além disso, o aumento dos níveis de aldosterona tem sido associado ao prejuízo do metabolismo da glicose e pode interagir com o tecido adiposo desregulando adipocinas inflamatórias, tais como a leptina. Este estudo teve como objetivo verificar a influência da obesidade nos níveis plasmáticos de aldosterona e leptina, bem como nos marcadores do metabolismo da glicose em indivíduos com hipertensão arterial resistente. MÉTODOS: Noventa e um pacientes foram divididos em dois subgrupos pela média de índice de massa corporal(IMC): (i) obesos (OBS, N=41, IMC>31,5kg/m2) e (ii) não obesos (nOBS, N=50, IMC<31,5kg/m2). Nós determinamos a composição corporal por bioimpedância (BIA 450). A glicemia de jejum, a hemoglobina glicada (HbA1c), bem como os níveis plasmáticos de aldosterona (radioimunoensaio) e leptina (ensaio imunoenzimático) também foram avaliados. RESULTADOS: O subgrupo OBS apresentou o metabolismo da glicose alterado pela glicemia de jejum (129±48 vs. 107±32mg/dL, p=0,04) e hemoglobina glicada (7,6±2,3 vs. 6,8±1,9%, p=0,03). Os níveis de aldosterona (137,9±102,0 vs. 92,6±67,9pg/ml, p=0,03), assim como os de leptina (24,4±17,2 vs. 36,4±23,5ng/ml, p=0,01)também estavam mais elevados em OBS quando comparados ao grupo nOBS. A análise de regressão linear múltipla indicou que o nível de glicose foi independentemente associado à obesidade em pacientes hipertensão arterial resistente. Conclusões: Nossos resultados demonstraram que o índice de massa corporal pode ser determinante para desregular o metabolismo da glicose, bem como os níveis de aldosterona e leptina em indivíduos hipertensos resistentes.

Efeitos renais da exposição crônica a nicotina em camundongos com deficiência de Klotho / Renal effects of chronic nicotine exposure in klotho deficient mice

A nicotina é o principal componente do tabaco e dos cigarros eletrônicos. A exposição crônica a nicotina, em quantidades semelhantes às atingidas pelo tabagismo humano, é responsável por piora da lesão renal aguda e da doença renal crônica. O gene klotho, predominantemente expresso no rim, foi descoberto após uma mutação insercional, com o surgimento de um fenótipo semelhante ao envelhecimento humano nos camundongos homozigotos para esse transgene. A proteína Klotho transmembrana tem ação de co-receptor do fator de crescimento fibroblástico 23 (FGF-23) e sua forma secretada atua em diversas vias intracelulares e em órgãos a distância. A deficiência de Klotho ocorre no envelhecimento, em situações que levam a lesão renal aguda e na doença renal crônica. A expressão reduzida de Klotho também agrava lesão renal aguda e participa da progressão da doença renal crônica, enquanto o seu aumento, ou a sua reposição, protegem dos processos inflamatórios e do estresse oxidativo. Neste estudo, objetivamos avaliar os efeitos renais, hemodinâmicos e sobre a expressão de Klotho da exposição crônica a nicotina e quais os efeitos dessa exposição nos animais haploinsuficientes para o transgene klotho (Kl+/-). Utilizamos para estas avaliações camundongos Kl+/- e seus controles wild type (Kl+/+), que foram expostos a nicotina (200 mcg/mL) ou veículo (sacarina 2%) diluídos em água por 28 dias. Ao final do estudo foram avaliados diurese, eletrólitos plasmáticos e urinários, ureia, aldosterona, ADH, FGF-23 e PTH intactos plasmáticos, expressão protéica renal de Klotho, alfa7-nAchR, NHE3, ENaC, NKCC2, AQP2, e-NOS, VEGF, MnSOD e renina, expressão genica renal de klotho, interleucinas, TBARS e GSH em tecido renal, taxa de filtração glomerular por FITC-inulina, pressão arterial e frequência cardíaca invasivas, sensibilidade baroreflexa e modulação autonômica cardíaca e periférica por análise espectral. Após a exposição a nicotina, os animais Kl+/+ apresentaram redução da expressão...

Nicotine is a major compound of tobacco and electronic cigarettes. Chronic exposure to nicotine concentrations that are similar to human smoke worsens acute kidney injury and chronic kidney disease. The klotho (Kl) gene is expressed predominantly by the kidney and was discovered after an unintentional insertional mutation that resulted, in transgenic homozygous mice, in a phenotype similar to human aging. Klotho transmembrane protein acts as a co-receptor to fibroblastic growth factor 23 (FGF-23) and the secreted form interacts in multiple intracellular pathways, with effects in distant organs. Klotho deficiency occurs in aging and in multiple acute kidney injury and chronic kidney disease etiologies, whereas klotho upregulation and replacement protect from inflammation and oxidative stress. Here, we investigated renal and hemodynamic effects of chronic nicotine exposure, its effects over renal expression of Kl, and compared wild type (Kl+/+) and Kl haploinsufficient mice (Kl+/-) in terms of the effects of that exposure. Kl+/- and Kl+/+ mice received nicotine (200 ?g/ml) or vehicle (saccharine 2%) in drinking water for 28 days. We evaluated diuresis, ions in serum and urine, urea, plasma and urinary levels of cotinine, aldosterone, plasma antidiuretic and parathyroid hormone, plasma FGF-23, protein expression of (immunoblotting for) Klotho and ?7 nicotinic acetylcholine receptor, NHE3, NKCC2, ENaC, aquaporin-2, e-NOS, VEGF and renin, klotho mRNA, kidney interleukines, TBARS and GSH, glomerular filtration rate by fluorescein isothiocyanate-inulin clearance, mean arterial pressure, heart rate, baroreflex sensitivity and autonomic cardiac and peripheral modulation by spectral analysis. After nicotine exposure, Kl+/+ mice showed decreased Klotho protein and mRNA and a tendency towards an elevation in plasma FGF-23, which were associated with both diuresis and glomerular filtration rate reductions, without modifications in ADH levels. Besides that, Kl+/+ animals...

Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide

The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.

Adenoma suprarrenal productor de aldosterona / Aldosterone-producing adrenal adenoma

La hipertensión arterial secundaria es más común en individuos menores de 30 años, la mayor parte son de causa renovascular; la etiología endocrina es excepcional, el hiperaldosteronismo primariosólo ocupa de 5-15%, el síndrome de Conn corresponde a 0.05-2.2% de la población de hipertensos y es una de las pocas causas potencialmente curables de hipertensión, por lo que consideramos este caso digno de ser revisado. Se presenta un hombre de 63 años de edad con hipertensión arterialdiagnosticada hace 25 años, en tratamiento con múltiples antihipertensivos, incluido el minoxidil sin control de cifras tensionales, que consulta a endocrinología por aparición de vello facial. Se consideró hipertensión arterial secundaria y se halló hipokalemia. La relación de aldosterona y renina elevada, sugería la presencia de hiperaldosteronismo, que se localizó con venografía de suprarrenales. La extirpación quirúrgica de la lesión confirmó el diagnóstico de adenoma adrenocortical. Después de la cirugía mejoró el control de la tensión arterial y tras suspender el minoxidil, la hipertricosis desaparece. (Acta Med Colomb 2014; 39: 191-195).

Secondary Hypertension is more common in individuals under 30; most have renovascular etiology; endocrine etiology is exceptional; primary hyperaldosteronism is only responsible for 5-15%, Conn syndrome corresponds to 0.05-2.2 % of the hypertensive population and is one of the few potentially curable causes of hypertension, so we consider this case worthy to be revised. A 63 year old man diagnosed with hypertension 25 years ago and treated with multiple antihypertensives including minoxidil, with uncontrolled blood pressure readings, which consults to endocrinology for appearance of facial hair, is presented. Secondary hypertension was considered, and hypokalemia was found. The ratio of aldosterone and high renin, suggested the presence of hyperaldosteronism which was localized by adrenal venography. Surgical removal of the lesion confirmed the diagnosis of adrenocortical adenoma. After surgery, control of blood pressure improved and after discontinuation of minoxidil, hypertrichosis disappears. (Acta Med Colomb 2014; 39: 191-195).

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.