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.

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.

Prueba de supresión con Dexametasona 1mg en una población de individuos con normopeso, sobrepeso y obesidad: Estudio multicéntrico / The Overnight 1mg Dexamethasone Test in Healthy Subjects with Normal Weight, Overweight and Obesity: a Multicentric Study

La prueba de supresión con dexametasona-1mg oral nocturna evalúa la conservación del mecanismo de retroalimentación negativa normal ejercido por los glucocorticoides sobre el eje hipotálamo-hipófiso-adrenal (HH-A), siendo ampliamente utilizada en el algoritmo diagnóstico de sospecha de síndrome de Cushing (SC). Pero la concentración de cortisol sérico matinal postinhibición que define la supresiblidad normal ha sido motivo de controversia, con valores variables desde el original =5 ug/dl (=138 nmol/L) hasta una cifra =1,8 ug/dl (=50 nmol/L) últimamente. Asimismo, es controvertida la respuesta en la obesidad, donde está descripta una alteración del eje H-H-A. Por lo tanto, el Departamento de Suprarrenal de SAEM llevó a cabo este estudio multicéntrico con el objetivo de definir la concentración de cortisol sérico obtenida luego de la administración de dexametasona 1mg nocturna, en una población de sujetos sanos de nuestro país con peso normal; concomitantemente, se evaluaron individuos con sobrepeso y con obesidad simple para comparar su respuesta respecto de los sujetos normopeso. Se estudiaron 80 individuos sanos, 60 mujeres y 20 hombres, de 15 a 66 años de edad, que fueron divididos en tres grupos según el índice de masa corporal (IMC): Normopeso, IMC=19-24,9 kg/m2, n=39; Sobrepeso, IMC=25-29,9 Kg/m2, n=21; y Obesos, IMC = 30 kg/m2, n=20. Se administró dexametasona 1 mg vía oral a las 23 hs. y se determinó la cortisolemia a las 8hs. de la mañana siguiente. Las determinaciones se centralizaron en un solo laboratorio y fueron realizadas por el equipo de radioinmunoensayo (RIA) de DSL, sensiblidad analítica de 0,5 ug/dl. Paralelamente en 10 sujetos, se determinó la cortisolemia postinhibición en las mismas muestras con otro equipo analítico, RIA-DPC. Resultados: Los resultados de la cortisolemia postsupresión en los tres grupos estudiados se expresan como X± DS (rango): en el grupo normopeso fue de 2,10± 0,77 ug/dl (0,78-3,40); en el sobrepeso, 1,94± 0,66 ug/dl (0,962,90); y en los obesos, 1,86 ± 0,63 ug/dl (0,85-3,30), no observándose diferencias significativas entre los tres grupos estudiados (test de Kruskall Wallis Dunn, p=0,319). En los 10 sujetos cuyas muestras fueron simultáneamente analizadas por RIA-DSL y por RIA-DPC, se observaron marcadas diferencias en 8/10, siendo la mediana de cortisol sérico obtenida por RIA-DPC de 0,5µg/dl, significativamente menor a la obtenida por RIA-DSL, de 2,2 µg/dl (test de Wilcoxon, p=0,002). Conclusiones: Debemos destacar que este es el primer estudio multicéntrico que evalúa la respuesta a la inhbibición con dexametasona 1 mg en nuestro medio. En esta primera etapa, demostramos que una concentración de cortisol sérico post 1 mg de dexametasona oral nocturna = 3,4 µg/dl (= 93,8nmol/l), determinada por RIA-DSL, caracteriza la respuesta normal de nuestra población de sujetos sanos. Ello es independiente del peso corporal, ya que los sujetos con normopeso, sobrepeso y obesidad suprimieron a valores similares. No se observó falta de supresión en ningún caso estudiado. Por otra parte, dadas las marcadas diferencias de valores halladas en las mismas muestras cuando son analizadas por equipos diferentes de RIA, es fundamental referir los resultados al método y equipo utilizados y estandarizar las pruebas clínicas con la metodología específica empleada en cada laboratorio.

The overnight oral dexamethasone test assesses the normal negative feedback of cortisol on the hypothalamic-pituitary-adrenal axis (H-P-A) 1. It is widely used in the screening of Cushing’s Syndrome (CS) 3,4,5. But the cut-off values for the normal response remains controversial: originally it was considered as 5 ug/dl and in the last years it was reported as 1.8 ug/dl 4. Likewise, there is no agreement about the suppression values in obesity, where a hyperactivity of the H-P-A axis has been reported. Therefore, the Adrenal Department of the Argentine Society of Endocrinology and Metabolism (SAEM) studied 80 healthy subjects recruited from ten hospitals of Buenos Aires in order to assess the normal response in our population. Sixteen women and twenty men, aged 15-66 years old (X = 39.2ys), were classified into three groups, according to their body mass index (BMI): normal weight, BMI- 19-24.9 kg/m2 (n= 39); overweight, BMI- 25-29.9 kg/m2 (n=21) and obese subjects, BMI> 30 kg/m2 (n=20). They had to be euthyroid and free of corticosteroid treatment, contraceptive pills, hormone replacement therapy, rifampicin and psychotropic drugs at the time of the study. Subjects referring drug abuse, alcoholism, depression, cardiovascular, and renal disorders and,obviously, adrenal diseases were excluded from the study. Dexamethasone 1mg per os was administered at 11p.m. and blood was withdrawn at 8 a.m. on the next morning to determine plasma cortisol concentration. Determinations were centralized in one laboratory and the RIA-DSL (Diagnostic System Laboratories-radioimmunoassay) was used. Additionally, in ten subjects plasma cortisol was also determined in the same blood samples by another radioimmunoassay kit, RIA-DPC (Diagnostic Products Corporation). The Kruskall-Dunn test was used to compare the plasma cortisol levels post-1mg dexamethasone among the three groups studied. In the 10 patients whose determinations were made in the same blood samples by two different RIA-kits (DSL and DPC),the Wilcoxon test was used to compare the results of plasma cortisol between RIA-DSL and RIA-DPC. Results: The results are expressed as X ± SD ug/dl (range). Plasma cortisol levels after 1mg-dexamethasone were: 2.10 ± 0.77 ug/dl ( 0.78- 3.40 ug/dl) in the normal weight goup; 1.94 ± 0.66 ug/dl (0.96-2.90) in the overweight group and 1.86 ± 0.63 ug/dl (0.85-3.30) in the obese subjects (Table I); no significant differences were observed among the three groups (p=0.319). According to these results, the cut-off value for plasma cortisol post-dexamethasone in the normal weight subjects was considered as = 3.4 ug/dl (93.8 nmol/L) using RIA-DSL. Similar suppression values were obtained in the overweight and obese subjects - 2.9 and 3.3 ug/dl, respectively. No false positive results were observed, either individually or in each group (Fig 1). In the 10 subjects whose blood cortisol was simultaneously determined in the same samples by RIA-DSL and RIA-DPC, the median for plasma cortisol was 2.2 ug/dl for the first and 0.5 ug/dl for the latter, respectively, with a significant difference between both RIA kits (p=0.002). (Table II). Conclusions: In this first stage, the present multicentric study shows that a plasma cortisol level post - 1mg dexamethasone suppression of = 3.4 ug/dl ( 93.8 nmol/L) defines our normal population response, with no significant differences among normal weight,overweight and obese subjects. Furthermore, we wish to point out that the cortisol values must be referred to the method and commercial kits used in each laboratory, since significant differences can be observed in the same blood samples when different kits are used, such as we and other authors have observed. We wish to remark the importance of our study, which is the first in its characteristics in Argentina. Furthermore, in a second stage, we plan to enlarge the sample number and to determine blood cortisol in the same samples by using different methods, in order to obtain a standardized cortisol suppression level. We also plan to study patients with confirmed CS and pseudocushing states in order to assess the sensitivity and specificity of the 1mg-dexamethasone suppression test in our population.

Retrospective multicentric study of pituitary incidentalomas.

Previously unsuspected pituitary tumors (incidentalomas) were analyzed in autopsies (4.8-27%) and magnetic resonance imaging (MRI) (10-37%), most of them being micro-pituitary incidentalomas (PI). However, patients with PIs sometimes had macroadenomas which may relate to previously unsuspected neurological and/or endocrine abnormalities. This study aims to establish the incidence of macro- vs. micro-PIs, the need for medical and/or surgical treatment and the neurological and endocrine dysfunction in a retrospective evaluation of patients with PIs studied over six years (1994-2000). Thirty-eight of 46 patients with PIs (22 males), aged 16-77, were followed for a mean of 3.2 years. Initial hormonal testing, ophthalmologic evaluation and MRI were repeated during follow-up. Twenty-nine (63%) of 46 patients had macro-PIs and 17 (17%) micro-PIs. Twenty-three males (75%) had macro-PIs, 10 (34.5%) with visual field defects. Consultations leading to PI diagnosis were chronic headache (28%), cranial trauma (15.3%), sinusitis (13%) and stroke (13%). Partial deficiencies of the anterior pituitary function were confirmed in 19 PIs (41.3%), with secondary hypogonadism prevailing (30%). Seven PIs (15%) were prolactinomas treated with dopamine agonists. Seventeen PIs (37%) underwent surgery. Immunohistochemical analysis showed gonadotrophinomas (30%), plurihormonal non-secreting adenomas (40%), and pituitary adenomas not reacting to any of the anterior pituitary hormone antibodies (30%). One operated macro-PI was a craniopharyngioma. Our data show a high percentage of PIs are macro-incidentalomas against expectations from necropsy and imaging studies. Most macro-PIs are found in males and are clinically non-functioning adenomas, 37% requiring surgery and hormonal substitution.

Enanismo asociado a panhipopituitarismo con neurohipófisis ectópica, sin diabetes insípida / Dwarfism associated at panhypopituitarism with ectopic neurohypophysis without diabetes insipidus

We are introducing a patient of 22 years old who suffers from Dwarfness and primary Amenorrhea. She showed dosages of basal somatotrophin and post estimulation of 0.5 ng/ml or less, somatomedin (IGF1): 2.40 ui/ml, rudiment uterus and annexes with normal karyotype 46xx. RMN of Sella Turcica and adjacencies showed; a posterior pituitary lobe ectopy, with the conservation of his hypothalamic conexion and hormonal deficit of L.A. (suprarenal, gonadal and somatotrophic axes). The use of RMN allowed us to evaluate and thus reached a precise diagnosis in reference to the hypothalamic lesion.

Enanismo asociado a panhipopituitarismo con neurohipófisis ectópica, sin diabetes insípida / Dwarfism associated at panhypopituitarism with ectopic neurohypophysis without diabetes insipidus

We are introducing a patient of 22 years old who suffers from Dwarfness and primary Amenorrhea. She showed dosages of basal somatotrophin and post estimulation of 0.5 ng/ml or less, somatomedin (IGF1): 2.40 ui/ml, rudiment uterus and annexes with normal karyotype 46xx. RMN of Sella Turcica and adjacencies showed; a posterior pituitary lobe ectopy, with the conservation of his hypothalamic conexion and hormonal deficit of L.A. (suprarenal, gonadal and somatotrophic axes). The use of RMN allowed us to evaluate and thus reached a precise diagnosis in reference to the hypothalamic lesion. (AU)