Hipertensão resistente em paciente com diagnótico de hiperaldosteronismo primário: resposta ao eplerenone / Resistant hypertension in a patient with primary hypereraldosteronism diagnosis: response to eplerenone

A maioria dos pacientes com hipertensão arterial (HA) não tem etiologia clara e é classificada como hipertensão primária. No entanto, 5% a 10% desses pacientes podem ter hipertensão secundária, o que indica presença de uma causa subjacente e potencialmente reversível. Em adultos com 65 anos ou mais, estenose da artéria renal aterosclerótica, insuficiência renal e hipotireoidismo são causas comuns. A hipertensão secundária deve ser considerada na presença de sintomas e sinais sugestivos, como hipertensão grave ou resistente, idade de início inferior a 30 anos (especialmente antes da puberdade), hipertensão maligna ou acelerada e aumento agudo da pressão arterial a partir de leituras previamente estáveis. Outras causas subjacentes da hipertensão secundária incluem hiperaldosteronismo, apneia obstrutiva do sono, feocromocitoma, síndrome de Cushing, doença da tireoide, coarctação da aorta e uso de certos medicamentos. A hipertensão arterial resistente (HAR) é definida quando a pressão arterial (PA) permanece acima das metas recomendadas com o uso de três anti-hipertensivos de diferentes classes, incluindo um bloqueador do sistema renina- -angiotensina (inibidor da enzima conversora da angiotensina [IECA] ou bloqueador do receptor de angiotensina [BRA]), um bloqueador dos canais de cálcio (BCC) de ação prolongada e um diurético tiazídico (DT) de longa ação em doses máximas preconizadas e toleradas, administradas com frequência, dosagem apropriada e comprovada adesão. Hipertensão arterial acompanhada de supressão da atividade da renina plasmática (ARP) e aumento da excreção de aldosterona caracteriza a síndrome de aldosteronismo primário. Esse quadro foi descrito, pela primeira vez em 1955 por Conn, em um paciente hipertenso grave hipocalêmico e com secreção elevada de aldosterona, que submetido à adrenalectomia direita resultou em cura da HA

Patients with arterial hypertension have no clear etiology and are classified as primary hypertension. However, 5% to 10% of these with hypertension may have the secondary form of disease, which indicates the presence of an underlying and potentially reversible cause. In adults aged 65 and over, the common causes of secondary hypertension are atherosclerotic renal artery stenosis, renal failure and hypothyroidism. Secondary hypertension should be considered in the presence of suggestive symptoms and signs, such as severe or resistant hypertension, age at onset less than 30 years (especially before puberty), malignant or accelerated hypertension and acute increase in blood pressure from previously stable readings. Other underlying causes of secondary hypertension include hyperaldosteronism, obstructive sleep apnea, pheochromocytoma, Cushing's syndrome, thyroid disease, coarctation of the aorta and use of others medications. Resistant arterial hypertension is defined when blood pressure remains above the recommended targets with the use of three antihypertensives of different classes, including a blocker of the renin-angiotensin system (inhibitor of the angiotensin-converting enzyme or angiotensin receptor blocker ), a calcium channel blocker and a thiazide diuretic in maximum recommended and tolerated doses, administered frequently, appropriate dosage and proven adherence. Arterial hypertension accompanied by suppression of plasma renin activity and increased aldosterone excretion characterizes the primary aldosteronism syndrome. This condition was described in 1955 by Conn, in a severe hypohypokalemic hypertensive patient with high aldosterone secretion, who underwent right adrenalectomy resulted in a cure for the hypertension

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.

Hipertensión arterial secundaria a hiperaldosteronismo primario / Hypertension secondary to primary hyperaldosteronism

RESUMEN La hipertensión arterial es una afección pandémica responsable de varias complicaciones cardiovasculares, neurológicas y renales. La gran mayoría se debe a la hipertensión esencial o primaria, pero cada vez se diagnostican más casos de hipertensión arterial secundaria, ya sea de causa endocrinológica, renal o neurológica. Se presenta un caso de hipertensión secundaria a hiperaldosteronismo primario.

ABSTRACT Hypertension is a pandemic worldwide, being responsible for several cardiovascular, neurological and renal complications. The vast majority is due to essential or primary hypertension, but more and more cases of secondary arterial hypertension are diagnosed, either due to endocrinological, renal or neurological causes. Next, an hypertension case of secondary to primary hyperaldosteronism is presented.

To compare the role on determining the functional location of primary hyperaldosteronism by multi-slice spiral CT and by adrenal vein sampling / 中华泌尿外科杂志

Objective To compare the role on determining the functional location of primary hyperaldosteronism (PHA)by multi-slice spiral CT (MSCT)and by adrenal vein sampling (AVS),and to discuss the reasonable method to use MSCT and AVS in localization diagnosis of PHA.Methods Clinical data of 78 patients with PHA were analyzed retrospectively.These patients were diagnosed in our department from June 2014 to June 2018.There were 27 male and 51 female patients.With mean age of (47.5 ± 11.2) years old.The mean systolic blood pressure was (190 ± 24)mmHg and mean diastolic blood pressure was (111 ± 16) mmHg.The mean history of hypertension was (6.0 ± 6.0) years.The mean serum potassium was (2.4 ± 0.6) mmol/L.The mean plasma aldosterone concentration (PAC) was (415.7 ± 235.4) pg/ml.The mean plasma renin activity (PRA) was (3.2 ± 5.7) ng/(ml · h).The mean aldosterone/renin ratio (ARR) was 409.0 ± 434.9.All PHA patients underwent MSCT and AVS,the accuracy on determining the functional location of PHA by MSCT and by AVS were evaluated based on the pathological results and clinical outcomes.The influence of adrenal size and character on the accuracy of determining the functional location of PHA by MSCT were analyzed.Results The rate of accuracy of determining the location of PHA by AVS was higher than that by MSCT[100.0％ (78/78) vs.71.8％ (56/78),P ＜ 0.05].When MSCT indicated:adrenal hyperplasia,adrenal tumor volume less than 1 cm,1 cm ＜ adrenal tumor volume ≤ 2 cm,adrenal tumor volume ＞ 2 cm,the rate of accuracy in localization diagnosis with MSCT was 50.0％ (4/8),81.0％ (17/21),92.9％ (26/28),100.0％ (9/9) respectively.Its trend has statistical significance (P ＜ 0.05).The diagnostic accuracy rate of MSCT for aldosterone adenoma was 79.6％ (43/54),while that of adrenal hyperplasia was 58.3 ％ (7/12).There was no statistical significance between two diagnostic accuracy rate of MSCT(P ＞ 0.05).Conclusions AVS is the gold standard for localization diagnosis.When MSCT indicates that there is no obvious abnormality in the adrenal gland,adrenal hyperplasia,small tumor (≤ 2 cm),and bilateral adrenal lesions,AVS should be examined at the same time,which can be considered as the gold standard for localization diagnosis.For isolated adrenal tumor (＞ 2 cm) in PHA,the accuracy of localization diagnosis in MSCT is very high and the AVS is unnecessary.

Rabdomiólisis por hipocalemia: manifestación atípica del síndrome de Conn / Rhabdomyolysis due to hypokalemia: an atypical manifestation of Conn's syndrome

Resumen La rabdomiólisis es una afección con espectro de manifestación amplio que puede cursar desde una enfermedad leve asintomática hasta complicaciones mortales por desequilibrio hidroelectrolítico, arritmias o lesión renal aguda. Se comunica el caso de una paciente de 35 años de edad, hipertensa, que ingresó por debilidad muscular posterior a un cuadro gastrointestinal. Tenía hipocalemia severa, elevación de creatincinasa, función renal conservada, hipocalcemia y alcalosis metabólica. Su evaluación integral culminó en el diagnóstico de hiperaldosteronismo primario secundario a un adenoma productor de aldosterona que fue removido de manera quirúrgica sin complicaciones. La manifestación del síndrome de Conn con rabdomiólisis por hipocalemia es excepcional porque la mayoría de los casos se diagnostican con normocalemia o hipocalemia leve a partir del protocolo de hipertensión secundaria. Es necesario un alto nivel de sospecha y evaluación integral para llegar al diagnóstico certero.

Abstract Rhabdomyolysis is a condition with a broad spectrum of presentation that can range from mild asymptomatic disease to fatal complications due to electrolyte imbalance, arrhythmias and/or acute renal injury. We report the case of a 35-year-old woman, hypertensive, who was admitted for muscle weakness following a gastrointestinal condition. Biochemically with severe hypokalemia, elevated creatinekinase, conserved renal function, hypocalcemia and metabolic alkalosis. Their comprehensive evaluation culminated in the diagnosis of primary hyperaldosteronism secondary to an aldosterone-producing adenoma which was surgically removed without complications. The presentation of Conn's syndrome with hypokalemia rhabdomyolysis is exceptional since most cases are diagnosed with normokalemia or mild hypokalemia from the secondary hypertension protocol. A high level of suspicion and integral evaluation are necessary to arrive at the correct diagnosis.

Glucose and lipid metabolism characteristics in the male primary aldosteronism patients / 国际检验医学杂志

Objective To investigate the characteristics of glucose and lipid metabolism in the male primary aldosteronism(PA) patients .Methods 125 male PA patients screened out by using plasma aldosterone/renin ratio(ARR) plasma aldosterone concen‐tration measurement were enrolled in the study(PA group) ,at the same time 127 male patients with essential hypertension(EH) were also recruited as EH group ,who had similar blood pressure levels and hypertension course .Clinical data and biochemical indi‐cators of each group were collected and the characteristics of glucose and lipid metabolism in the male PA patients were analyzed . Results Serum potassium level of PA group was lower than EH group(P<0 .05) .Compared with EH group ,there were significant increase of triglycerides concentration in PA group(P<0 .05) ,and significant decrease of HDL‐C concentration in PA group(P<0 .05) .Oral glucose tolerance test(OGTT) 2 h glucose level and waist in PA group were higher or larger than that in EH group (P<0 .05) .Conclusion Compared with EH patients ,glucose and lipid metabolism disorder are more severe in male PA patients , the symptoms are mainly abdominal obesity and impaired glucose tolerance .

Incidentally Discovered Aldosterone and Cortisol Cosecreting Adrenal Cortical Adenoma / 이화의대지

A substantial proportion of adrenal incidentalomas demonstrates subtle hormonal hypersecretion; however, adenomas that cosecrete aldosterone and cortisol are rare. We here report a case of an adrenal mass that was incidentally detected on a computed tomography scan in a 57-year-old man. The patient had a 10-year history of diabetes mellitus and a 5-year history of hypertension. Evaluation revealed hyperaldosteronemia with an elevated plasma aldosterone-to-renin ratio, hypokalemia, unsuppressed cortisol after dexamethasone administration, and elevated urinary free cortisol concentration. The appearance of the right adrenalectomy specimen indicated adrenal adenoma. Postoperatively, the blood glucose and blood pressure control improved and the urinary cortisol and aldosterone-to-renin ratio normalized. A complete endocrine evaluation in patients with incidentally discovered adrenal masses should be performed, even if the patient has a long-standing history of hypertension and diabetes, to avoid any postoperative adrenal crises.

Medición de la concentración plasmática de renina inmunoreactiva por un método automatizado y su correlación con la actividad de renina plasmática / Measurement of Immunoreactive Plasma Renin Concentration by an Automated Method and its Correlation with Plasma Renin Activity

Está en discusión si la concentración de renina inmunoreactiva (CR) aporta la misma información que la actividad de renina plasmática (ARP), pero sí está demostrado que el índice aldosteronemia / ARP (ARR) presenta un mayor valor predictivo positivo que las determinaciones aisladas de ARP y de aldosterona (A) para el tamizaje del hiperaldosteronismo primario (HAP). En un estudio experimental prospectivo de 227 muestras consecutivas correspondientes a individuos ambulatorios, ninguno de ellos con diagnóstico definitivo de HAP, nos propusimos evaluar 1) la correlación de los resultados de un método automatizado para medir CR (LIAISON, DiaSorin) respecto de los de ARP (RIA, DiaSorin). 2) La Concordancia Diagnóstica Presuntiva (CDP) entre los resultados bioquímicos de CR y ARP. 3) La correlación entre los resultados de los cocientes A/CR (ACR) y ARR. Resultados: Hemos observado una correlación altamente significativa (p < 0,0001) entre los resultados de ARP y CR, con una CDP del 83 % para concentraciones medias y altas de ARP. Sin embargo, la CDP es menor y no aceptable para concentraciones bajas de ARP (< 1,3 ng/mL/hora). La correlación entre los resultados de ACR y ARR fue altamente significativa (p < 0,0001). Conclusiones: El método de CR sería de utilidad para un estudio inicial del paciente con el fin de descartar HAP. Para CR bajas, debería recurrirse a la medición de ARP que presenta mayor sensibilidad para valores bajos de Renina (R). Estudios poblacionales con mayor número de individuos son necesarios para confirmar estos resultados preliminares.

It is under discussion whether the results of immunoreactive renin concentration (RC) provide the same information as plasma renin activity (PRA). Additionally, it has been suggested that the determination of the aldosteronemia / PRA ratio (ARR) has a higher positive predictive value than isolated determinations of PRA and aldosterone (A) for screening of primary hyperaldosteronism (PHA). We designed an experimental and prospective study of 227 consecutive samples from ambulatory individuals, none of them with a definitive diagnosis of PHA. Our objective was to evaluate: 1) the correlation of results from an automated method to measure RC (LIAISON, DiaSorin) with respect to the PRA. (RIA, DiaSorin). 2) the presumptive diagnosis concordance (PDC) between the results of RC and PRA. 3) the correlation between the results of of the A/CR ratio (ACR) and ARR. Results: There is a high significant correlation (p < 0.0001) between results of PRA and RC, with a PDC = 83 % for regular and high PRA. However, PDC is low and not acceptable for low levels of PRA (< 1.3 ng/mL/hr). The correlation between the results of A/RC ratio (ACR) and ARR is highly significant (p < 0.0001). Conclusions: RC methodology would be useful for an initial study of a patient, in order to rule out PHA. For low levels of RC, would be necessary to additionally measure PRA, since it has higher sensitivity for low Renin (R) concentrations. Additional population studies with higher number of individuals will be necessary to confirm this preliminary data.

The association between KCNJ5 gene polymorphism and primary hyperaldosteronism / 中华内分泌代谢杂志

Objective To investigate the association between KCNJ5 gene polymorphism and primary hyperaldosteronism(PA).Methods A total of 248 PA patients and 816 essential hypertension (EH) patients were enrolled in this study,TaqMan assay was used to detect the rs1221497 polymorphism of KCNJ5 gene.Results The genotypes of rs1221497 were in Hardy-Weinberg equilibrium in both PA group and EH group,the genotype frequencies ofGG,GC,CC were 208,39,1 in PA group and 631,177,8 in EH group respectively,the allele frequencies in the two groups were 455,41 and 1 439,193 respectively.The frequencies of GG genotype and G allele in PA group were significantly higher than those in EH group.Logistic regression showed that GG genotype was closely associated with PA after adjusting age.Conclusions GG genotype and G allele may contribute to the occurrence of PA.

Association of KCNJ5 gene missense mutations with aldosterone-producing adenoma and primary hyperaldosteronism / 中华内分泌代谢杂志

Objective This study is about to detect the KCNJ5 gene variations in aldosterone-producing adenoma (APA) with primary hyperaldosteronism (PA),and to investigate the association of the KCNJ5 gene missense mutations with APA and PA.Methods A total of 46 APA tumors and their clinical characteristics were collected from Hypertension Center of the People's Hospital of Xinjiang Uygur Autonomous Region,and all the tumors were confirmed by pathology.All the samples of the coding region segments of KCNJ5 were detected by PCR and direct DNA sequencing to compare the different missense mutations in the tumor cells and peripheral blood cells and to analyze the association between the genotype and phenotype.Results Three missense mutations were found in 46 patients with APA:c.451G ＞ C/A (p.G151R) (5/46),c.503T ＞ G (p.L168R) (4/46),c.830T ＞ A (p.S209T) (12/46).S209T,as an unreported somatic mutation was observed.There were no missense mutations detected in the peripheral blood.Sex,age,systolic blood pressure,diastolic blood pressure,duration of hypertension,plasma potassium,urine potassium,aldosterone,plasma renin activity,aldosterone,and plasma renin activity ratio,as well as the rate of positive family history were compared between the mutants and wild-types.Systolic blood pressure and plasma potassium level among G151 R,L168R,and S209T had statistical differences.Systolic blood pressure in G151R was significantly higher than the other two groups,while the plasma potassium level was significantly lower than the other groups.Conclusions Three missense mutations were found in 46 patients with APA.The subjects with mutations had more serious condition than those without mutations after comparing their clinical phenotype.Besides,other different subtypes may exist in PA.

Hiperaldosteronismo primario: el gran olvidado en pacientes con hipertensión de inicio temprano y de difícil control, enfoque y manejo / Primary aldosteronism: the forgotten one in patients with early-onset hypertension, and difficult control, approach and management

El hiperaldosteronismo primario es una enfermedad que se caracteriza por la producción autónoma en exceso de aldosterona, que tiene como resultado la supresión de los niveles de renina, causando con frecuencia hipertensión arterial e hipokalemia. El hiperaldosteronismo primario es más común de lo que se pensaba. La alta prevalencia, el daño que causa al sistema cardiovascular y a los riñones, y el hecho de que un diagnóstico y tratamiento oportunos puedancorregir la hipertensión y la hipokalemia, justifican la búsqueda del hiperaldosteronismo primarioen muchos pacientes con hipertensión. Cuando se sospecha hiperaldosteronismo primario, sedeben realizar pruebas de tamización; la prueba de elección es la relación entre la concentración de aldosterona plasmática y la actividad de la renina plasmática. Posteriormente, se debe confirmar el diagnóstico con alguno de los métodos disponibles, como la carga oral de sodio o la prueba de infusión de solución salina, entre otros. Una vez se confirma el diagnóstico, el paso a seguir es determinar el subtipo de hiperaldosteronismo primario, lo cual es importante para determinar eltratamiento más adecuado. Finalmente, se deben hacer estudios de imaginología para identificar posibles lesiones en las glándulas adrenales.

Abstract: primary aldosteronism is a disease characterized by autonomous excess production of aldosterone, which results in the suppression of renin levels, often causing hypertension and hypokalemia. Primary hyperaldosteronism is more common than previously thought. The high prevalence causes damage to the cardiovascular system and kidneys, and the fact that a diagnosis and treatment can correct the hypertension and hypokalemia justifies the search of primary hyperaldosteronism in many patients with hypertension. When primary aldosteronism is suspected, screening tests should be performed; the recommended test is the aldosterone to renin ratio. Subsequently, the diagnosis should be confirmed by any of the available methods, such as the oral sodium loading test and saline infusion test, among others. After confirming the diagnosis, the next step is to determine the subtype of primary aldosteronism, which is important in determining the most appropriate treatment. Finally, imaging studies should be carried out to identify possible lesions in the adrenal glands.

A Rare Case of Primary Hyperparathyroidism Associated with Primary Aldosteronism, Hurthle Cell Thyroid Cancer and Meningioma

Multiple endocrine neoplasia type 1 (MEN1) syndrome includes varying combinations of endocrine and non-endocrine tumors. There are also a considerable number of atypical MEN1 syndrome. In this case, a 68-yr-old woman was referred to the Department of Endocrinology for hypercalcemia. Five years ago, she had diagnosed as primary hyperaldosteronism and now newly diagnosed as parathyroid hyperplasia with laboratory and pathologic findings. Hurthle-cell thyroid cancer was also resected during the parathyroid exploration and small meningioma was found on brain MRI. Her general condition has markedly improved and her adrenal mass and meningioma are being closely observed now. We could find the loss of heterozygosity of the MEN1 locus in parathyroid glands, suggesting a MEN1-related tumor, but not a germline mutation. Considering a variety of phenotypic expression and a limitation of current molecular analysis, periodic follow up will be needed in patients with a MEN1-like phenotype.

Hipertensión arterial maligna e hiperaldosteronismo hiperreninémico: reporte de un caso / Malignant arterial hypertension and hyperreninemic hyperaldosteronism: a case report

Se presenta el caso de una mujer de 28 años de edad, hospitalizada por hipertensión arterial severa, edema pulmonar e hipokalemia. se encontró hiperaldosteronismo hiperreninémico e imagen de una lesión nodular en la glándula suprarrenal izquierda, la cual fue extirpada mediante cirugía laparoscópica. El estudio histológico demostró hiperplasia macronodular cortical y en el postoperatorio, hubo retorno progresivo de la hipertensión e hipokalemia

Determinación del valor de corte de la relación aldosterona/actividad de renina plasmática para la detección de hiperaldosteronismo primario en hipertensión arterial esencial: estudio multicéntrico / Determination of the Aldosterone/Plasma Renin Activity Ratio for the Screening of Primary Hyperaldosteronism in Essential Hypertension: a Multicentric Study

El hiperaldosteronismo primario (HAP) es una afección caracterizada por la producción inapropiadamente elevada y una relativa autonomía del sistema renina-angiotensina. Estimaciones previas, basadas sólo en la evaluación de hipertensos con hipokalemia, consideraban al HAP como una causa poco frecuente de hipertensión (1%). Sin embargo, estudios actuales fundamentados en el cálculo de la relación aldosterona/ actividad de renina plasmática (RAA) arrojan una incidencia mayor (5-10%), siendo la hipertensión arterial (HTA) normokalémica la presentación más frecuente. Dada la amplitud de los valores de corte de la RAA, el Departamento de Suprarrenal de SAEM diseñó un estudio multicéntrico prospectivo en una población de Argentina con el objetivo de establecer nuestro propio valor y determinar así la prevalencia de HAP. Fueron estudiados 353 individuos de ambos sexos, 104 controles normotensos, sin antecedentes familiares de HTA y 249 pacientes hipertensos. Se indicó dieta normosódica y la suspensión de antihipertensivos que interfieran con el eje mineralocorticoideo. Las determinaciones de la actividad de renina plasmática (ARP), DIA-SorinRIA, y de aldosterona, RIA-DPC, fueron realizadas en un único laboratorio. Se realizó ionograma y se evaluaron parámetros clínicos y bioquímicos de síndrome metabólico. La RAA calculada según el percentilo 95 en los controles, fue establecida en la cifra de 36 como valor de corte para sospechar HAP en los hipertensos, requiriéndose una concentración de aldosterona >15 ng/ml. Con una RAA≥36, se realizaron pruebas confirmatorias de sobrecarga salina o de fludrocortisona. La RAA fue ≥36 en 31/249 pacientes, confirmándose HAP en 8 (7 adenomas y 1 hiperplasia), con una prevalencia del 3.2%. Los restantes no completaron estudios confirmatorios. La presencia de síndrome metabólico fue similar en los hipertensos con y sin HAP. En conclusión, este primer estudio multicéntrico argentino determinó nuestro valor de corte de la RAA en 36. Su aplicación permitió establecer una prevalencia de HAP del 3,2% que, aunque podría estar subestimada, resulta significativamente mayor que la previa histórica y concuerda con la incidencia referida en la bibliografía.

Primary hyperaldosteronism (PHA) or Conn's disease was classically suspected in the presence of hypertension (H) and hypokalemia. It was previously considered as a rare cause of H, being reported in only 1% of hypertensive patients. It can be caused by an adrenal adenoma (the former usual presentation) or by adrenal hyperplasia. But since the use of the aldosterone/plasma renin activity ratio (AAR) as the screening method in the last years, it is currently considered as almost the most frequent cause of secondary H., accounting for 5-10% of essential H. Plasma rennin activity (PRA) determination is a laborious procedure with low reproducibility and it directly affects the AAR; thus each laboratory must assess its own cut-off value. Therefore, in the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM), we performed this multicentric prospective study of a population of Argentina with the aim of assessing our own AAR cut-off level in normotensive controls in order to apply it for PHA screening in essential hypertensive patients. We studied 353 adult subjects: 104 controls, aged 45,18 ± 13,78 years-old ( X±SD), with no history of arterial hypertension in their first-degree relatives and with two separate day-registry of blood pressure≤ 139/85 mmHg and 249 hypertensive patients, aged 51± 13,6 years-old ( X ± SD), with arterial blood pressure≥ 140/90 mmHg in the sitting position. Subjects with cardiac, renal, hepatic and neurological diseases were excluded as well as those with Cushing´s syndrome, hyperthyroidism, untreated hypothyroidism, diabetes mellitus and patients under glucocorticoids, oral contraceptive pills or estrogen therapy. A normal sodium diet was indicated and potassium was supplemented when needed. Blood was withdrawn between 8 and 10:00 a.m. with the subjects in the upright position. Aldosterone (A) was determined by DPC radioimmunoassay (RIA) and PRA, by DIA-Sorin RIA. The A normal levels are 4-30 ng/dl for ambulatory individuals on a normal sodium diet and the PRA normal values are < 3,3 ng/ml/h. In order to avoid false positive results in the hypertensive group, AAR was calculated when A was above 15 ng/dl. We measured the waist circumference and we determined the body mass index. Blood sodium, potassium, calcium, urea, creatinine, cholesterol, HDL-C, LDL-C, triglyceride and liver function tests were performed. Statistical Analysis and Results Since the AAR variable showed a non-normal distribution, the cut-off value was considered as the 95th percentile in the control group, which was calculated as 36. This is also in accordance to the function of the empirical distribution of Collings and Hamilton. In our 249 hypertensive patients, 31 had an AAR ≥ 36. PHA was confirmed in 8: seven has an adrenal adenoma and one had hyperplasia. The prevalence of PHA in our population was 3,2 %, with a 95th confidence interval ranging from 1,4 to 6,2 %. In the remaining 23 patients, confirmatory tests could not be completed. There was no correlation between the severity of the hypertension and the AAR value, with no statistical significant differences between those with or without PHA. Likewise, we found no correlation between PRA and advancing age. In hypertensive patients, metabolic syndrome was more prevalent than in controls, but it was present to the same extent in those with or without PHA. Conclusions To our knowledge, this is the first multicentric study performed in Argentina to determine the aldosterone/ plasma renin activity ratio in our normotensive control population. Our AAR value of 36 agrees with the levels reported in the international literature: thus an AAR ≥ 36 along with an aldosterone ≥ 15 ng/ml in hypertensive patients lead us to suspect PHA and to perform confirmatory tests. Applying these criteria, we found a prevalence of 3,2% of PHA in essential HTA. It is possible that this value may be underestimated due to the fact that confirmatory tests could not be completed in all the hypertensive subjects with an AAR≥ 36. In spite of this, our prevalence is significantly greater than the historical one and it lies in the range reported in the literature.

A Case of Primary Aldosteronism due to Remnant Adenoma after Adrenalectomy in Pregnant Woman / 대한신장학회지

Primary aldosteronism is present in approximately 1 percent of hypertensive patients, and is rarely associated with pregnancy. We report a case of unilateral aldosterone producing adenoma in a pregnant woman. A 29-year-old woman was referred to with hypertension and proteinuria at 14 weeks' gestation. She had known that she had unilateral aldosterone producing adenoma for 18 months and refused medical or surgical treatment. She was prescribed antihypertensive medication and preformed laparoscopic adrenalectomy in left adrenal gland at 22 weeks' gestation. After adrenalectomy, her blood pressure was normal. At 29 weeks' gestation, she complained headache, and her blood pressure was 200/100 mmHg with pitting edema. We thought preeclampsia and performed cesarean section. After the baby was delivered, she had uncontrolled hypertension, hypokalemia with persistent proteinuria. We checked plasma renin activitity, aldoterone and abdminopelvic computed tomography. We found remnant left adrenal adenoma and perfomed laparoscopic operation. After reoperation, her blood pressure was normal and no proteinuria.

Primary Hyperaldosteronism with Increased Plasma Renin Activity due to Secondary Hypertensive Renal Impairment / 대한내분비학회지

An increased plasma aldosterone concentration, with suppressed plasma renin activity (PRA), is an abnormal finding in primary hyperaldosteronism. A suppressed PRA is caused by aldosterone- dependent sodium retention and extracellular volume expansion. A case of primary hyperaldosteronism, due to adenoma, with increased PRA, was observed. An adrenalectomy and intraoperative renal biopsy was performed. In our patient, histologically proven renal arteriosclerosis was the probable cause of the escape of the PRA from the suppression by an aldosterone-producing adenoma. Normal blood pressure was not attained after the adrenalectomy. However, the blood pressure was then controlled by small doses of antihypertensive drug before resection of the tumor. In this case, the patient was treated with spironolactone, but the blood pressure was not correctly controlled. After the adrenalectomy, the blood pressure was well controlled with smaller dose of calcium channel blockers. So, an early adrenalectomy may be beneficial as soon as the diagnosis of an aldosterone-producing adenoma is confirmed, even in patients with hypertensive nephrosclerosis.