Adrenal vein sampling versus CT scan to determine treatment in primary aldosteronism: an outcome-based randomised diagnostic trial.
The distinction between unilateral aldosterone-producing adenoma or bilateral adrenal hyperplasia as causes of primary aldosteronism is usually made by adrenal CT or by adrenal vein sampling (AVS). Whether CT or AVS represents the best test for diagnosis remains unknown. We aimed to compare the outcome of CT-based management with AVS-based management for patients with primary aldosteronism.



In a randomised controlled trial, we randomly assigned patients with aldosteronism to undergo either adrenal CT or AVS to determine the presence of aldosterone-producing adenoma (with subsequent treatment consisting of adrenalectomy) or bilateral adrenal hyperplasia (subsequent treatment with mineralocorticoid receptor antagonists). The primary endpoint was the intensity of drug treatment for obtaining target blood pressure after 1 year of follow-up, in the intention-to-diagnose population. Intensity of drug treatment was expressed as daily defined doses. Key secondary endpoints included biochemical outcome in patients who received adrenalectomy, health-related quality of life, cost-effectiveness, and adverse events. This trial is registered with ClinicalTrials.gov, number NCT01096654.



We recruited 200 patients between July 6, 2010, and May 30, 2013. Of the 184 patients that completed follow-up, 92 received CT-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist) and 92 received AVS-based treatment (46 adrenalectomy and 46 mineralocorticoid receptor antagonist). We found no differences in the intensity of antihypertensive medication required to control blood pressure between patients with CT-based treatment and those with AVS-based treatment (median daily defined doses 3·0 [IQR 1·0-5·0] vs 3·0 [1·1-5·9], p=0·52; median number of drugs 2 [IQR 1-3] vs 2 [1-3], p=0·87). Target blood pressure was reached in 39 (42%) patients and 41 (45%) patients, respectively (p=0·82). On secondary endpoints we found no differences in health-related quality of life (median RAND-36 physical scores 52·7 [IQR 43·9-56·8] vs 53·2 [44·0-56·8], p=0·83; RAND-36 mental scores 49·8 [43·1-54·6] vs 52·7 [44·9-55·5], p=0·17) for CT-based and AVS-based treatment. Biochemically, 37 (80%) of patients with CT-based adrenalectomy and 41 (89%) of those with AVS-based adrenalectomy had resolved hyperaldosteronism (p=0·25). A non-significant mean difference of 0·05 (95% CI -0·04 to 0·13) in quality-adjusted life-years (QALYs) was found to the advantage of the AVS group, associated with a significant increase in mean health-care costs of €2285 per patient (95% CI 1323-3248). At a willingness-to-pay value of €30 000 per QALY, the probability that AVS compared with CT constitutes an efficient use of health-care resources in the diagnostic work-up of patients with primary aldosteronism is less than 0·2. There was no difference in adverse events between groups (159 events of which nine were serious vs 187 events of which 12 were serious) for CT-based and AVS-based treatment.



Treatment of primary aldosteronism based on CT or AVS did not show significant differences in intensity of antihypertensive medication or clinical benefits for patients after 1 year of follow-up. This finding challenges the current recommendation to perform AVS in all patients with primary aldosteronism.



Netherlands Organisation for Health Research and Development-Medical Sciences, Institute of Cardiology, Warsaw.
Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Tanja
T
Dekkers
Department of Hypertension, Institute of Cardiology, Warsaw, Poland.
Aleksander
A
Prejbisz
Department of Radiology, Radboud University Medical Center, Nijmegen, Netherlands.
Leo J Schultze
LJS
Kool
Department of Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands.
Hans J M M
HJMM
Groenewoud
Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands.
Marieke
M
Velema
Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, Netherlands.
Wilko
W
Spiering
Department of Hypertension, Institute of Cardiology, Warsaw, Poland.
Sylwia
S
Kołodziejczyk-Kruk
Department of Radiology, Radboud University Medical Center, Nijmegen, Netherlands.
Mark
M
Arntz
Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland.
Jacek
J
Kądziela
Department of Urology, Radboud University Medical Center, Nijmegen, Netherlands.
Johannes F
JF
Langenhuijsen
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Michiel N
MN
Kerstens
Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
Anton H
AH
van den Meiracker
Department of Internal and Vascular Medicine, Academic Medical Center, Amsterdam, Netherlands.
Bert-Jan
BJ
van den Born
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Fred C G J
FCGJ
Sweep
Department of Internal Medicine, Division of Endocrinology, Radboud University Medical Center, Nijmegen, Netherlands.
Ad R M M
ARMM
Hermus
Department of Hypertension, Institute of Cardiology, Warsaw, Poland.
Andrzej
A
Januszewicz
Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, Netherlands.
Alike F
AF
Ligthart-Naber
Department of Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands.
Peter
P
Makai
Department of Health Evidence, Radboud University Medical Center, Nijmegen, Netherlands.
Gert-Jan
GJ
van der Wilt
Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, Netherlands; Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany.
Jacques W M
JWM
Lenders
Department of Internal Medicine, Division of Vascular Medicine, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address: jaap.deinum@radboudumc.nl.
Jaap
J
Deinum
D000306:Adrenal Cortex Neoplasms / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging* / Q000601:surgery; D000311:Adrenal Glands / Q000000981:diagnostic imaging* / Q000473:pathology; D000315:Adrenalectomy; D018246:Adrenocortical Adenoma / Q000097:blood / Q000150:complications / Q000000981:diagnostic imaging* / Q000601:surgery; D000328:Adult; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000097:blood / Q000000981:diagnostic imaging* / Q000209:etiology / Q000628:therapy; D006965:Hyperplasia / Q000150:complications; D008297:Male; D008875:Middle Aged