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.

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.

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.

Influence of preoperative propranolol on cardiac index during the anhepatic phase of liver transplantation / Influência do propranolol pré-operatório no índice cardíaco durante a fase anepática do transplante hepático / Influencia del propranolol preoperatorio en el índice cardíaco durante la fase anhepática del trasplante hepático

INTRODUCTION: Liver transplantation is the best therapeutic option for end-stage liver disease. Non-selective beta-blocker medications such as propranolol act directly on the cardiovascular system and are often used in the prevention of gastrointestinal bleeding resulting from HP. The effects of propranolol on cardiovascular system of cirrhotic patients during liver transplantation are not known. OBJECTIVE: Evaluate the influence of propranolol used preoperatively on cardiac index during the anhepatic phase of liver transplantation. METHOD: 101 adult patients (73 male [72.2%]) who underwent cadaveric donor orthotopic liver transplantation by piggyback technique with preservation of the retrohepatic inferior vena cava performed at Hospital das Clinicas, Federal University of Minas Gerais were evaluated. There was no difference in severity between groups by the MELD system, p = 0.70. The preoperative use of propranolol and the cardiac index outcome were compared during the anhepatic phase of liver transplantation in 5 groups (I: increased cardiac index, II: cardiac index reduction lower than 16%, III: cardiac index reduction equal to or greater than 16% and less than 31%, IV: cardiac index reduction equal to or greater than 31% and less than 46%, V: cardiac index reduction equal to or greater than 46%). RESULTS: Patients in group I (46.4%) who received propranolol preoperatively were statistically similar to groups II (60%), III (72.7%), IV (50%) and V (30.8%), p = 0.57. CONCLUSION: The use of propranolol before transplantation as prophylaxis for gastrointestinal bleeding may be considered safe, as it was not associated with worsening of cardiac index in anhepatic phase of liver transplantation. .

INTRODUÇÃO: O transplante hepático (TH) é a melhor opção terapêutica para doença hepática em estágio terminal (DHET). As medicações betabloqueadoras não seletivas, como o propranolol, atuam diretamente no sistema cardiovascular (SCV) e são frequentemente usadas na prevenção de hemorragia digestiva decorrente da HP. Os efeitos do propranolol no SCV de cirróticos durante o TH não são conhecidos. OBJETIVO: Avaliar a influência do uso pré-operatório do propranolol no índice cardíaco (IC) durante a fase anepática do TH. MÉTODO: Avaliaram-se 101 pacientes adultos (73 homens, 72,2%) submetidos a transplante ortotópico de fígado doador cadáver, pela técnica de piggyback com preservação da veia cava inferior retro-hepática, feito no Hospital das Clínicas da Universidade Federal de Minas Gerais. Não houve diferença de gravidade pelo sistema MELD entre os grupos, p = 0,70. Foram comparados o uso pré-operatório de propranolol com o desfecho do IC durante a fase anepática do TH em cinco grupos (I: aumento do IC; II: redução do IC inferior a 16%; III: redução do IC igual a ou maior do que 16% e menor do que 31%; IV: redução do IC igual a ou maior do que 31% e menor do que 46%;V: redução do IC igual a ou maior do que 46%). RESULTADOS: Pacientes que fizeram uso pré-operatório de propranolol no grupo I (46,4%) foram estatisticamente semelhantes aos dos grupos II (60%), III (72,7%), IV (50%) e V (30,8%), p = 0,57. CONCLUSÃO: O propranolol no pré-transplante, como profilaxia para hemorragia digestiva, pode ser considerado seguro, pois não se associou à pioria do IC na fase anepática do TH. .

INTRODUCCIÓN: El trasplante hepático (TH) es la mejor opción terapéutica para la enfermedad hepática en estado terminal. Los betabloqueantes no selectivos, como el propranolol, actúan directamente en el sistema cardiovascular y a menudo son usadas en la prevención de la hemorragia digestiva proveniente de la hipertensión portal. Los efectos del propranolol en el sistema cardiovascular de cirróticos durante el TH no se conocen. OBJETIVO: Evaluar la influencia del uso preoperatorio del propranolol en el índice cardíaco (IC) durante la fase anhepática del TH. MÉTODO: Se estudiaron 101 pacientes adultos (73 hombres [72,2%]) sometidos a trasplante ortotópico de hígado de donante cadáver, por la técnica de piggyback con preservación de la vena cava inferior retrohepática, en el Hospital das Clínicas de la Universidad Federal de Minas Gerais. No hubo diferencia respecto a la gravedad por el sistema Meld entre los grupos (p = 0,70). Se comparó el uso preoperatorio del propranolol con el resultado del IC durante la fase anhepática del TH en 5 grupos (i: aumento del IC; ii: reducción del IC < 16%; iii: reducción del IC ≥ 16% y < 31%; iv: reducción del IC ≥ 31% y < 46%;v: reducción del IC ≥ 46%). RESULTADOS: El número de pacientes que usaron el propranolol en el preoperatorio en el grupo i (46,4%) fue estadísticamente similar a los grupos ii (60%), iii (72,7%), iv (50%) y v (30,8%), p = 0,57. CONCLUSIÓN: El propranolol en el pretrasplante, como profilaxis para la hemorragia digestiva, puede ser considerado seguro porque no se asoció con el empeoramiento del IC en la fase anhepática del TH. .

Changes in the clinical manifestations of primary aldosteronism

BACKGROUND/AIMS: Primary aldosteronism (PA) is now widely recognized to have a higher prevalence than was once thought. In view of its increasing prevalence, we compared chronological changes in clinical manifestations of PA according to different times of diagnosis. METHODS: In total, 85 patients diagnosed with PA from January 1986 through March 2012 were reviewed retrospectively, based on their medical records. During two periods-1986 to 2005 and 2006 to 2012-41 and 44 patients, respectively, were diagnosed with PA. We compared the clinical and biological characteristics of PA between these periods. RESULTS: The results demonstrate an increasing trend in the prevalence of idiopathic hyperaldosteronism (IHA; p = 0.19). In the 2006 to 2012 period, patients with PA presented with higher serum potassium levels at the time of diagnosis than in the 1986 to 2005 period (p < 0.0002). Adrenal vein sampling (AVS) was performed mostly in the latter period (82.3%) and the diagnostic accuracy of adrenal computed tomography, compared with AVS, was only 56.2%. About 78.0% versus 86.3% of patients had at least one target organ damage (TOD) in the 1986 to 2005 and 2006 to 2012 periods, respectively (p = 0.39). However, patients with TOD were older and had longer durations of hypertension than patients without, in both periods. CONCLUSIONS: PA is becoming more prevalent. There was an increasing tendency for IHA, and more PA patients presented with normokalemia than in the earlier period. Early and accurate diagnosis of PA with AVS and proper treatment should have substantial prognostic value.

Clinical characteristics and follow-up of Korean patients with adrenal incidentalomas

BACKGROUND/AIMS: We investigated the clinical characteristics and follow-up findings of subjects with adrenal incidentalomas in a single, tertiary-care hospital in South Korea. METHODS: The study consisted of a retrospective analysis of 282 adrenal incidentaloma patients who underwent radiographic and endocrinological evaluations at Samsung Medical Center in Seoul, South Korea, between January 2004 and July 2011. RESULTS: Most (86.2%) of the subjects were found to have nonfunctioning tumors. Functioning tumors were seen in 39 patients (13.8%). Among them, 28 (9.9%) had subclinical Cushing syndrome (SCS), six (2.1%) had pheochromocytoma, and five (1.8%) had primary hyperaldosteronism. Malignant adrenal tumors were discovered in three cases: two (0.7%) were primary adrenal cancers, and one (0.4%) was a secondary metastasis from a lung cancer. Significant risk factors for functional tumors were female gender (odds ratio [OR], 3.386; 95% confidence interval [CI], 1.611 to 7.117; p = 0.0013) and a noncontrast attenuation value of > 10 Hounsfield units (OR, 2.806; 95% CI, 1.231 to 6.397; p = 0.0141). During follow-up (mean, 22.5 months) of 72 of the patients, three (4.2%) developed hormonal changes due to functional tumors. One was confirmed as pheochromocytoma by histopathology, and the others were diagnosed with SCS and followed routinely without surgical intervention. No malignant transformation was found in these patients. CONCLUSIONS: Based on these findings, initial hormonal and radiographic evaluations for adrenal incidentalomas appear to be more important than follow-up tests because functional or malignant changes are rare.

Utilidad de la relación aldosterona y actividad renina plasmática en el diagnóstico de hiperaldosteronismo primario / Aldosterone/renin ratio in the diagnosis of primary aldosteronism

El hiperaldosteronismo primario (HP) es la forma más común de hipertensión arterial (HTA) secundaria. Recientemente varios estudios sugieren que la prevalencia de esta enfermedad varía entre 5% y 15% entre la población hipertensa, y 20% para hipertensión arterial refractaria. El objetivo de este estudio fue, ante la gran variabilidad de prevalencias sobre HP según las publicaciones internacionales y pocos datos en la Argentina, aportar la prevalencia de HP en un hospital general del interior del país, relacionándolo con el grado de HTA y presencia de normokalemia. En este estudio transversal se realizó dosaje de A/ARP en 123 pacientes hipertensos, suspendiendo toda medicación que interfiriera en los dosajes hormonales; se utilizó como método confirmatorio el test de solución salina (SS) para el diagnóstico de HP y la tomografía computarizada (TC) de abdomen para el diagnóstico etiológico del HP. Se detectó una relación A/ARP elevada en 20 (16.4%) pacientes. En 18 se realizó el test de SS, confirmando el diagnóstico de aldosteronismo en 8 (6.5% del total). En la TC, dos presentaron adenomas, y seis glándulas suprarrenales normales. Todos los pacientes con HP pertenecían al grupo II y III de HTA según el VI Joint National Committee (VI JNC) y el 50% fue normokalémico. Encontramos una prevalencia de 6.5% de HP, asociado a grado II y III de hipertensión, y valores de potasio normal en la mitad de los pacientes.

Primary aldosteronism (PA) is a possible cause of endocrine hypertension. Recent studies have suggested a prevalence ranging between 5% and 15% of all hypertensive patients, and 20% in patients with refractory hypertension.The objective of this transversal study was to establish the prevalence of PA in a hypertensive population using the aldosterone / plasma renin ratio (ARR) as a screening method, considering that the prevalence rates for PA among hypertensive people present a wide range and that there are only few reports in Argentina. This ratio was then related with the degree of hypertension and with the presence or absence of hypokalemia. Serum aldosterone and plasma renin activity levels were measured in 123 hypertensive patients after discontinuing all medications that could interfere with the hormonal tests. Patients with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test (SST) to confirm the diagnosis of PA, followed by computed tomography (CT) of the abdomen. Twenty patients presented an ARR > 25 (16.4%). Eighteen were submitted to the SST, eight had a diagnosis of PA confirmed with positive SST (6.5%). Of 8 patients who underwent an abdominal CT, two showed adenoma, and six normal adrenal anatomy. All the eight patients with a PA diagnosis belonged to group II and III of hypertension according to Joint National Committee VI (JNC VI), and only 4 (50%) were normokalemic. We found a 6.5% prevalence of PA, associated with grade II and III hypertension, and normal potassium values in half of the patients with PA.

Prevalência do hiperaldosteronismo primário em uma liga de hipertensão arterial sistêmica / Prevalencia del hiperaldosteronismo primario en una liga de hipertensión arterial sistémica / Prevalence of primary hyperaldosteronism in a systemic arterial hypertension league

FUNDAMENTO: Até recentemente, o hiperaldosteronismo primário era considerado uma causa rara de hipertensão secundária. Porém, ao longo dos últimos anos, muitos estudos têm sugerido que essa doença pode afetar até 20 por cento dos hipertensos. OBJETIVO: Determinar a prevalência do hiperaldosteronismo primário em pacientes hipertensos em tratamento na liga de hipertensão de um hospital universitário. MÉTODOS: Foram realizadas dosagens de aldosterona sérica e atividade plasmática da renina em 105 pacientes, em vigência do tratamento anti-hipertensivo usual, excetuando-se aqueles em uso de beta-bloqueadores e espironolactona, em jejum e após repouso na posição deitada por 20 minutos. Aqueles com relação aldosterona/atividade plasmática da renina maior que 25 foram submetidos ao teste de supressão com sobrecarga salina endovenosa e, após a confirmação da autonomia da secreção de aldosterona, foi realizada tomografia computadorizada das adrenais. Os resultados são apresentados como porcentagens, médias e desvios-padrão. RESULTADOS: Dos 105 pacientes, 6,54 por cento eram hipertensos refratários. Nove apresentaram relação aldosterona/atividade plasmática da renina > 25 (8,5 por cento do total). Destes, oito foram submetidos ao teste de supressão e um (hipertenso refratário) teve o diagnóstico confirmado de hiperaldosteronismo primário (0,96 por cento do total). Foi realizada tomografia computadorizada de adrenais, sendo considerada normal. CONCLUSÃO: A prevalência do hiperaldosteronismo primário na amostra estudada foi de 0,96 por cento do total. No entanto, quando avaliados apenas os portadores de hipertensão refratária, a prevalência foi de 14,3 por cento.

BACKGROUND: Until recently, primary hyperaldosteronism was considered a rare cause of secondary hypertension. However, in recent years, many studies have suggested that this disease can affect up to 20 percent of hypertensive individuals. OBJECTIVE: To determine the prevalence of primary hyperaldosteronism in hypertensive patients treated at the hypertension league of a university hospital. METHODS: Serum aldosterone and plasma renin activity levels were measured in 105 patients while they were undergoing standard antihypertensive treatment, with the exception of those using betablockers and spironolactone, in fasting condition and after rest in the supine position for 20 minutes. Those with an aldosterone/plasma renin activity ratio > 25 were submitted to the saline suppression test and, after the confirmation of the autonomy of aldosterone secretion, a computed tomography of the adrenals was performed. The results are presented as percentages and means and standard deviations. RESULTS: Of the 105 patients, 6.54 percent presented refractory hypertension. Nine presented an aldosterone/plasma renin activity ratio > 25 (8.5 percent of the total). Of these, 08 were submitted to the saline suppression test and 01 (with refractory hypertension) had the diagnosis of primary hyperaldosteronism confirmed (0.96 percent of the total). A computed tomography of the adrenals was performed, which showed normal results. CONCLUSION: The prevalence of primary hyperaldosteronism in the studied sample was 0.96 percent of the total. However, when only the patients with refractory hypertension were evaluated, the prevalence was 14.3 percent.

FUNDAMENTO: Hasta recientemente, se consideraba el hiperaldosteronismo primario como una causa rara de hipertensión secundaria. Sin embargo, a lo largo de los últimos años, muchos estudios han sugerido que esa enfermedad puede afectar hasta el 20 por ciento de los hipertensos. OBJETIVO: Determinar la prevalencia del Hiperaldosteronismo Primario en pacientes hipertensos en tratamiento en la Liga de Hipertensión de un Hospital Universitario. MÉTODOS: Se realizaron dosificaciones de aldosterona sérica y actividad plasmática de la renina en 105 pacientes, en vigencia del tratamiento antihipertensivo usual, excepto aquellos en uso de betabloqueantes y espironolactona, en ayuno y tras guardar reposo en posición acostada por 20 minutos. Aquellos con relación aldosterona/actividad plasmática de la renina mayor que 25 se sometieron a prueba de supresión con sobrecarga salina endovenosa y, luego de la confirmación de la autonomía de la secreción de aldosterona, se realizó tomografía computarizada de las adrenales. Los resultados se presentan como porcentajes, promedios y desviaciones estándar. RESULTADOS: De los 105 pacientes, el 6,54 por ciento eran hipertensos refractarios. Nueve presentaron relación aldosterona/actividad plasmática de la renina > 25 (8,5 por ciento del total). De estos, ocho se sometieron al examen de supresión y uno (hipertenso refractario) tuvo el diagnóstico confirmado de Hiperaldosteronismo Primario (el 0,96 por ciento del total). Se realizó una tomografía computarizada de adrenales, que estaba normal. CONCLUSIÓN: La prevalencia del Hiperaldosteronismo Primario en la muestra estudiada fue del 0,96 por ciento del total. Sin embargo, cuando se evaluaron sólo los portadores de hipertensión refractaria, la prevalencia fue del 14,3 por ciento.

Marcadores de inflamación endotelial subclínica en una familia con hiperaldosteronismo familiar tipo I por mutación de novo / Subclinical endothelial inflammation markers in a family with type I familial hyperaldosteronism caused by a de novo mutation

Background: Type I familial hyperaldosteronism is caused by the presence of a chimaetic gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activityregulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation. Aim: To evaluate subclinical endothelial inflammation markers, Me Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation. Patients and methods: We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by ¡ong-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13year-old boy with hypertension stage 2 (in agree to The JointNational Committee VII, JNC-vIl), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively. Results: All affected subjects had approximately a 50 percent increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment. Conclusions: We report a family canying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.

The syndromes of low-renin hypertension: "separating the wheat from the chaff"

Hiperaldosteronismo primário (HAP) é caracterizado por hipertensão com renina baixa, com ou sem hipocalemia, compreendendo o adenoma produtor de aldosterona (APA) e a hiperplasia adrenal bilateral ou HA idiopático (HAI). Em séries recentes usando a relação aldosterona (aldo, ng/dL):renina (ng/mLúh) (RAR) para rastreamento, a prevalência de HAP atinge 8-20% dos hipertensos; a predominância atual do HAI (>80%) sobre APA sugere a inclusão de hipertensos essenciais com renina baixa (HERB), nos quais aldo pode ser suprimida por expansão de volume. Avaliamos as características do teste RAR, obtido retrospectivamente de 127 pacientes com HAP (81 APA; 46 HAI) e 55 com hipertensão essencial (30 HERB; 25 com renina normal, HERN) estudados de 1975 a 1990. Usando a combinação de cutoffs de 27 para RAR e de 12ng/dL para aldo, obtivemos sensibilidade (S) de 89,8% e especificidade (E) de 98,2% na separação entre HAP e HE: todos os APA e 72% dos HAI (mas apenas um [3%] HERB) tinham valores acima destes limites. Dentre os 46 HAI, 10 (21,7%) tinham RAR <27 e destes, 4 tinham aldo <12ng/dL, virtualmente indistingüíveis dos HERB. Valores mais elevados de cutoff (RAR >100; aldo >20) permitem 84% de S e 82,6% de E na separação entre APA e HAI. Como HAI e HERB ("o joio") devem ser estágios do espectro de uma mesma doença, parece irrelevante a separação dessas entidades. Entretanto, identificação precisa do APA ("o trigo") é fundamental, por ser a única forma de HAP curável cirurgicamente. Assim, enquanto a suspeita de um APA precisa ser criteriosamente investigada e tratada cirurgicamente, pacientes com doença não tumoral (HAI e HERB) podem ser tratados com antagonistas do receptor de aldo, que também previnem os efeitos inflamatórios envolvidos no processo de fibrose e remodelação anormal do miocárdio.

Conn's Syndrome Associated with Behcet's Disease

A 39-yr-old woman, who had been treated for Behcet's disease for 4 yr, was admitted for further investigation of recently identified hypokalemia and hypertension. Suppressed plasma renin activity with elevated plasma aldosterone concentration and an anomalous postural decrease in plasma aldosterone were observed. An abdominal CT scan revealed a right adrenal mass. The patient was diagnosed with Conn's syndrome. The association of Conn's syndrome with Behcet's disease was thought to be coincidental. To our knowledge, this is the first case of Conn's syndrome associated with Behcet's disease.