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Ambulatory Blood Pressure Monitoring in Secondary Arterial Hypertension Due to Adrenal Diseases Michele Ceruti, MD;1 Luigi Petramala, MD;1 Dario Cotesta, MD;1 Sabrina Cerci, MD;4 Valentina Serra, MD;1 Chiara Caliumi, MD;1 Monica Iorio, MD;1 Giorgio De Toma, MD;2 Antonio Ciardi, MD;3 Domenico Vitolo, MD;3 Claudio Letizia, MD1
The aim of this study was to evaluate ambulatory blood pressure monitoring in patients with essential hypertension and hypertension caused by adrenal pathology. Sixty-six patients with primary aldosteronism, 37 with pheochromocytomas, and 45 with adrenal incidentalomas were included. These patients were compared with 152 essential hypertensive patients and 64 normotensive subjects. Ambulatory blood pressure monitoring evaluated daytime and nighttime systolic and diastolic blood pressure and heart rate. The authors found that the “nondipper” phenomenon was present in 51.5% of patients with primary aldosteronism, 43.2% with pheochromocytomas, 42.2% with incidentalomas, 34.2% with hypertension, and 15% of subjects who were normotensive. In 58% of primary aldosteronism patients with idiopathic adrenal hyperplasia, there was an absence of the physiologic blood pressure nocturnal fall (nondipper), which was statistically significant (P10 mm Hg). These subjects are known as nondippers, whereas subjects with normal circadian rhythm are known as dippers.17–19 Studies using ABPM have reported that the reduction in nighttime BP is less in some secondary forms of hypertension.20,21 The mechanisms of these findings are not fully understood. The aim of our study was to assess the behavior of BP by ABPM in patients with adrenal VOL. 8 NO. 9 SEPTEMBER 2006
The Journal of Clinical Hypertension® (ISSN 1524-6175) is published monthly by Le Jacq, Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2006 by Le Jacq, All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at
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hypertension. Patients with EH and healthy subjects were recruited as controls. MATERIALS AND METHODS Patients A large series of patients with arterial hypertension due to adrenal diseases were consecutively enrolled in our Day Hospital of Internal Medicine and Hypertension at the University of Rome “La Sapienza,” Rome, Italy, from January 2000 to December 2005. Patients were divided into the following groups: (1) 66 patients with primary aldosteronism (PA) (33 men and 33 women; mean age, 48±13 years), (2) 37 patients with adrenal pheochromocytoma (PHEO) (23 men and 14 women; mean age, 47±15 years), and (3) 45 patients with adrenal incidentaloma (INC) (21 men and 24 women, mean age, 50±13 years). The control groups consisted of 152 patients with EH (76 men and 76 women; mean age, 49±12 years) without any sign of target organ damage and 64 normotensive subjects (23 men and 41 women; mean age, 50±11 years). None of the patients with adrenal disease and EH at diagnosis were treated with antihypertensive drugs for at least 4 weeks before the ABPM studies. Diagnosis of Adrenal Diseases Primary Aldosteronism. After an overnight fast and 1 hour of resting in the sitting position, a captopril test was performed between 7 AM and 9 AM. Plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (PC) were measured at baseline and again at 60 minutes after captopril (50 mg PO) administration. BP values were measured at baseline and after captopril with a Riva-Rocci sphygmomanometer using phase V for the diastolic reading. All patients with a PA/PRA (ng/dL:ng/mL/h) ratio ≥40 at baseline or ≥30 after captopril underwent a confirmation test. Two liters of saline (NaCl, 0.9%) were infused over 4 hours while the patients were kept in the supine position. PRA, PA, and PC were measured at baseline and again at the end of the saline infusion. An imaging test comprising high-resolution computed tomography (CT) with 3-mm slices and systematic use of a contrast medium and/or magnetic resonance imaging (MRI) was mandatory in all patients with a positive screening test and PA values >7.5 ng/dL after saline infusion, regardless of PA/PRA ratio. All patients had to undergo adrenal vein sampling, even if there was no evidence of adrenal nodules. Drugs affecting the renin-angiotensin-aldosterone system were not given to any patients.
VOL. 8 NO. 9 SEPTEMBER 2006
In all cases, the diagnosis of adrenal cortical adenoma (APA) was confirmed by histopathologic diagnosis, while idiopathic adrenal hyperplasia (IHA) diagnosis was performed by technical imaging (e.g., adrenal vein sampling) Pheochromocytoma. The diagnosis of PHEO was established on the basis of: (1) clinical symptoms (such as headache, tachycardia, hyperidrosis, and paroxysmal hypertension), and (2) elevated levels of 24-hour urinary metanephrines and/or elevated plasma metanephrine levels. In all patients, tumors were radiologically evident on CT or MRI scans. Monoiodobenzylguanidine scintigraphy was performed in patients if the CT or MRI scans did not show an adrenal mass. Adrenal INC. In accordance with the definition of INC (adrenal mass incidentally discovered during a radiologic procedure performed for symptoms not correlated to adrenal diseases), hormonal data were obtained in all patients to exclude a secretive function. Patients who presented with a history of neoplasia that frequently metastasize to the adrenal gland, such as lung, breast, kidney, and skin tumors, were excluded. Baseline hormonal evaluations included diurnal rhythm of PC, urinary free cortisol, plasma adrenocorticotropic hormone, plasma D4 androstenedione, plasma dehydroepiandrosterone sulphate, plasma 17α-hydroxyprogesterone, plasma testosterone, supine and upright PRA and PA, urinary excretion of metanephrines, and aldosterone. Tests included an overnight 1-mg dexamethasone suppression test. The demonstration of autonomous PC secretion in patients with INC helped to identify the socalled subclinical Cushing’s syndrome (SCS).22 In the present study, we adopted criteria of 2 or more abnormal results in tests of the hypothalamic-pituitary-adrenal axis (such as the association of lack of PC suppressibility after 1 mg dexamethasone with either low adrenocorticotropic hormone levels and/or abnormal urinary free cortisol excretion) for defining SCS.23 No patients with Cushing’s syndrome were found. In patients with normal hormonal data, the diagnosis of nonfunctioning adrenal adenoma was made. Essential Arterial Hypertension. The diagnosis of EH was established based on the absence of clinical history and laboratory data of secondary hypertension: principally normal values for plasma and urinary electrolytes, renal function, urinary
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The Journal of Clinical Hypertension® (ISSN 1524-6175) is published monthly by Le Jacq, Three Parklands Drive, Darien, CT 06820-3652. Copyright ©2006 by Le Jacq, All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publishers. The opinions and ideas expressed in this publication are those of the authors and do not necessarily reflect those of the Editors or Publisher. For copies in excess of 25 or for commercial purposes, please contact Sarah Howell at
[email protected] or 203.656.1711 x106.
®
metanephrine, the renin-angiotensin-aldosterone system, urinary free cortisol, and calcium-phosphorus system. All patients with white coat hypertension were excluded from the study. Ambulatory BP Monitoring ABPM was performed using the oscillometric technique, which involves a portable lightweight, noninvasive monitor with a self-insufflating cuff (Spacelabs Medical, 90207, Issaquah, WA). 24 ABPM readings were obtained at 15-minute intervals from 6 AM to midnight and at 30-minute intervals from midnight to 6 AM. The following ABPM parameters were evaluated: average daytime SBP; average daytime diastolic BP (DBP) and daytime heart rate (when awake); average nighttime SBP; average nighttime DBP and nighttime heart rate (when asleep); and average 24-hour SBP, average 24-hour DBP, and average 24-hour heart rate. Periods were determined by the subjects’ diaries. The definitions of dipper and nondipper were established where nighttime SBP and DBP decrease was >10% and 125/80 mm Hg.26,27 Subjects without a complete 24-hour BP measurement (14 diurnal and 7 nocturnal measurements) were excluded from the study. STATISTICAL ANALYSES All data are reported as mean ± SD. The statistical analyses were performed with SigmaStat software (Aspire Software, Leesburg, VA), and all values were analyzed using the analysis of variance test, followed by the Student t test, whenever appropriate. A P value of
