ABSTRACT
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.
ABSTRACT
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.