Radiol Oncol 2020; 54(4): 409-418. doi: 10.2478/raon-2020-0052
409
research article
Adrenal vein sampling for primary 
aldosteronism: a 15-year national referral 
center experience
Tomaz Kocjan1,2, Mojca Jensterle1,2, Gaj Vidmar2,3,4, Rok Vrckovnik1,2, Pavel Berden2,5, 
Milenko Stankovic2,5
1 Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia
2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 
3 University Rehabilitation Institute, Ljubljana, Slovenia
4 FAMNIT, University of Primorska, Koper, Slovenia
5 Clinical Institute of Radiology, University Medical Centre Ljubljana, Ljubljana, Slovenia
Radiol Oncol 2020; 54(4): 409-418.
Received 14 April 2020
Accepted 12 July 2020
Correspondence to: Prof. Tomaž Kocjan, M.D., Ph.D., Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical 
Centre Ljubljana, Zaloška 7, SI-1525 Ljubljana, Slovenia. E-mail: tomaz.kocjan@kclj.si
Disclosure: No potential conflicts of interest were disclosed.
Background. Adrenal vein sampling (AVS) is essential for diagnostics of primary aldosteronism, distinguishing uni-
lateral from bilateral disease and determining treatment options. We reviewed the performance of AVS for primary 
aldosteronism at our center during first 15 years, comparing the initial period to the period after the introduction of a 
dedicated radiologist. Additionally, AVS outcomes were checked against CT findings and the proportion of operated 
patients with proven unilateral disease was estimated.
Patients and methods. A retrospective cross-sectional study conducted at the national endocrine referral center 
included all patients with primary aldosteronism who underwent AVS after its introduction in 2004 until the end of 2018. 
AVS was performed sequentially during Synacthen infusion. When the ratio of cortisol concentrations from adrenal 
vein and inferior vena cava was at least 5, AVS was considered successful. 
Results. Data from 235 patients were examined (168 men; age 32–73, median 56 years; BMI 18–48, median 30.4 kg/
m2). Average number of annual AVS procedures increased from 7 in the 2004–2011 period to 29 in the 2012–2018 
period (p < 0.001). AVS had to be repeated in 10% of procedures; it was successful in 77% of procedures and 86% of 
patients. The proportion of patients with successful AVS (92% in 2012–2018 vs. 66% in 2004–2011, p < 0.001) and of suc-
cessful AVS procedures (82% vs. 61%, p < 0.001) was statistically significantly higher in the recent period. 
Conclusions. Number of AVS procedures and success rate at our center increased over time. Introduction of a 
dedicated radiologist and technical advance expanded and improved the AVS practice.
Key words: angiography; adrenal gland; endocrine disorders; secondary hypertension
Introduction
Primary aldosteronism is the most common form 
of secondary hypertension, with a prevalence of 
5.9% among hypertensive patients in primary care 
practice.1 Autonomous and excessive secretion of 
aldosterone from one or both adrenal glands in 
patients with primary aldosteronism causes sig-
nificantly higher cardiovascular risk and more pro-
nounced renal damage compared to equally severe 
essential hypertension.1–3 Amongst available tar-
geted treatment, the preferred therapeutic option 
is unilateral laparoscopic adrenalectomy, which 
can normalize or decrease blood pressure in most 
patients with proven unilateral disease.4,5 Long-
term medical treatment with mineralocorticoid 
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism410
receptor antagonists is not only more expensive 
and less convenient, but it might also have worse 
outcomes overall.4,6 
Therefore, a crucial part of diagnostic workup 
in primary aldosteronism is to correctly determine 
which patients have unilateral disease and could 
pursue surgical cure. Adrenal computed tomogra-
phy (CT) (or magnetic resonance imaging (MRI)) 
should be the first test in the subtype evaluation of 
primary aldosteronism and to exclude adrenocor-
tical carcinoma.4 However, because of increasing 
prevalence of nonfunctioning adrenal incidentalo-
mas, the reliability of CT in localizing unilateral 
disease (e.g. an aldosterone producing adenoma) 
declines with patient age.4,7 In most patients CT 
cannot accurately distinguish between unilateral 
and bilateral forms, and may even lead to inappro-
priate treatment of primary aldosteronism.8 The 
only exception are infrequent younger patients be-
low 35 years of age with florid disease and a clear 
one-sided adrenal adenoma with normal contralat-
eral gland.4,8,9
All other surgical candidates should proceed to 
adrenal vein sampling (AVS), which is regarded 
as the gold standard to demonstrate lateralization 
and to avoid unnecessary or inappropriate adre-
nalectomy. More than 50 years after its introduc-
tion, AVS remains controversial as an invasive, 
expensive and a technically challenging method 
with successful bilateral catheterization obtained 
in only about 75% of cases.4,10 Cannulation of the 
small and short right adrenal vein with direct 
drainage into the inferior vena cava (IVC) is often 
the main obstacle to a successful procedure, while 
the sampling from the left adrenal vein is relatively 
straightforward. There is substantial inconsistency 
in how AVS is performed and interpreted. When 
done by experienced radiologists, the complication 
rate is low at between 0.2 and 0.9%.11 Only a limit-
ed number of referral centers worldwide routinely 
carry out the procedure.10,12 Recently, the introduc-
tion of cone beam CT (CBCT) and other technical 
developments have further improved the AVS suc-
cess rate and reduced the complications.13–16
Primarily, we aimed to review the performance 
of AVS for primary aldosteronism at our center 
from its introduction in 2004 up to 2018. The initial 
period from 2004 to 2011 was compared to the peri-
od after the introduction of a dedicated radiologist 
in 2012. Our secondary objectives were to check the 
outcomes of AVS against CT findings and to esti-
mate the proportion of patients with proven unilat-
eral disease who ultimately had surgery.
Patients and methods
Study design
We conducted a retrospective cross-sectional study 
from AVS introduction in November 2004 to the 
end of 2018 at the Slovenian national tertiary endo-
crine referral center, which serves a country with 
a population of 2 million inhabitants. All the data 
originated from the Slovenian AVS database. The 
data collection and its analysis were approved by 
the National Medical Ethics Committee.
Patients
All patients with confirmed primary aldosteron-
ism who underwent AVS at our center during the 
study period were suitable for enrollment. The di-
agnostic work-up for primary aldosteronism was 
done according to the established guidelines4,17, as 
previously detailed elsewhere.18 
Radiological imaging
One to three months before the AVS,  all patients 
but one had adrenal imaging with a dual-source 
computed tomography (CT) scanner (Somatom 
Dual Source, Siemens, Germany). Our pre-speci-
fied adrenal CT protocol included 1 mm axial slices 
through the abdomen before, and if necessary also 
FIGURE 1. Tiny aldosterone-producing adenoma (8 mm) in lateral limb of the right 
adrenal gland (arrow) (CT scan). 
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism 411
after, the intravenous administration of 80–100 ml 
of iodinated contrast (370 mgJ/mL), injected at a 
rate of 3–4 ml/s via antecubital vein during breath-
holding. Contrast-enhanced images were acquired 
after 60 seconds and 15 minutes. The standard 
scanning parameters included beam collimation of 
64x0.6 mm, 16 slices and gantry rotation time of 0.5 
s. Tube voltage was set at 120 kV, while the tube 
current was variable, optimized for body mass in-
dex and size, ranging between 160 and 210 mA. 
Source images of all phases were reconstructed on 
the axial plane at 5 mm, and on the coronal planes 
at 4 mm. Since 2017 a new-generation CT scan-
ner (Somatom Force, Siemens, Germany) has been 
used, which allowed for more precise adaptation 
to the individual patient body characteristics. The 
scanning protocol remained essentially the same 
except for axial reconstructions at 2 mm. In 2014, 
interdisciplinary meetings dedicated to adrenal 
pathology were introduced where CT scans were 
meticulously reassessed with a radiologist, if both 
adrenals were described as normal. Finally, any 
thickening of at least 5 mm was deemed abnormal 
(Figure 1). The interventional radiologist also re-
viewed the images, in order to recognize the adre-
nal veins, especially on the right side.
Adrenal vein sampling
AVS was executed after an overnight fast between 
8 and 9 AM. All patients were in the recumbent po-
sition for at least 1 hour before sampling. Infusion 
of synthetic adrenocorticotropic hormone (ACTH) 
Synacthen (50 μg/h) was started 30 min before AVS 
and continued throughout the procedure. 
During local anesthesia, a 5 Fr sheath (Avanti+ 
Introducer, Cordis, USA in the first period; 
Radiofocus Introducer II, Terumo, Japan in the re-
cent period) was introduced into the right femoral 
vein. AVS was performed sequentially with the right 
adrenal vein always being cannulated and sampled 
first, using a 5 Fr Mickelson catheter (Cook Medical 
Inc., USA) or a 5 Fr Cobra C2 catheter with open-
ended tip and two side-holes (Cordis, USA) in the 
first period. In the recent period a 4 Fr Mickelson 
catheter (Cook Medical Inc., USA) was routinely 
used on the right side (Figure 2). Catheterization 
of the left renal vein then followed with the same 
catheter, which was used as a guide for a 2.7 Fr 
Progreat microcatheter (coaxial type with catheter 
and guidewire; Terumo Interventional Systems, 
USA) to cannulate the common trunk of the left in-
ferior phrenic vein and the left adrenal vein. The 
corresponding blood sample was drawn either at 
the junction of these two veins or selectively from 
the left adrenal vein above the junction (Figure 3). 
Finally, a microcatheter was removed and the 
Mickelson catheter slightly pulled out to sample 
blood from the infra-renal IVC. On the other hand, 
a 4 Fr MPA 2 catheter with open-ended tip and two 
side-holes (Cordis, USA) was used on the left side 
in the first period. Standard 0.035-inch guidewire 
(J Tef Guidewire, Kimal, UK) was used in all cases. 
Additionally, 0.035-inch guidewire with J angled 
FIGURE 3. Branches of the left adrenal vein during sampling (arrows) (angiography).
FIGURE 2. The right adrenal vein during sampling (arrow) (angiography).
Radiol Oncol 2020; 54(4): 409-418.
Kocjan T et al. / Adrenal vein sampling for primary aldosteronism412
tip (Terumo, Japan) was used on the left side in the 
first period. Blood samples were drawn in 5 ml sy-
ringes and sent to laboratory for aldosterone and 
cortisol measurements. Hemostasis at the puncture 
site was ensured by manual compression.
During the initial period from 2004 to 2011 there 
were two interventional radiologists perform-
ing AVS; from 2012 onwards all procedures were 
done by a single dedicated interventional radiolo-
gist. During the first period, AVS was performed 
with fluoroscopic guidance by digital subtrac-
tion angiography (INTEGRIS V5000; Philips, The 
Netherlands), which was later changed to single-
plane digital subtraction angiography (Allura Xper 
FD; Philips, The Netherlands). In the majority of 
cases, small amounts of contrast (90 ml on average 
per procedure in the first period and 52 ml on av-
erage per procedure in the recent period, respec-
tively) were injected to better visualize the right 
adrenal vein. 
High-resolution CBCT (Phillips Allura XperCT, 
The Netherlands) acquisition during AVS has been 
used since 2012 at first sporadically and then more 
consistently to identify the tip of the catheter ac-
curately, in order to differentiate between the right 
adrenal vein and a hepatic accessory vein or a para-
vertebral vein when necessary (Figure 4).
The average AVS procedure time decreased 
from 18.2 minutes in the first period to 16.8 min-
utes in the recent period.
When the selectivity index (SI), computed as the 
ratio of concentrations of cortisol from an adrenal 
vein and the infra-renal IVC, was at least 5, AVS 
was deemed successful. Lateralization index (LI), 
defined as the ratio of the higher over the lower 
cortisol–corrected aldosterone ratio, of more than 
4 indicated unilateral aldosterone excess, while the 
values between 3 and 4 were assumed borderline.19 
Suppressed plasma renin activity (PRA) values (< 
0.6 ng/mL/h) were used as proof for unlikely stim-
ulation of the contralateral adrenal cortex at a level 
adequate to confound interpretation of lateraliza-
tion.20,21
Assays
Serum aldosterone was measured with the Active® 
Aldosterone RIA (Beckman Coulter, Immunotech, 
Czech Republic). Serum cortisol was measured 
with an automated chemiluminescent immunoas-
say (CLIA) on the Immulite® 2000 XPi (Siemens 
Healthcare, Gwynedd, United Kingdom). The re-
spective within- and between-assay coefficients of 
variation were below 4.5% and 9.8% for aldosterone 
and below 6.8% and 9.4% for cortisol. PRA meas-
urements were performed using the Angiotensin 
I RIA KIT (Beckman Coulter, Immunotech, Czech 
Republic). The respective within- and between-as-
say coefficients of variation were below 11.3% and 
20.9%.
Statistical analysis
Descriptive statistics were calculated. Patient char-
acteristics and outcomes were compared between 
periods or groups using t-test, exact Mann-Whitney 
test and Fisher’s exact test. Cohen’s kappa was used 
to assess agreement between diagnostic methods. 
Statistical analyses were conducted using IBM SPSS 
Statistics 20 (IBM Corp., Armonk, USA, 2011).
Results
Data from 235 patients with primary aldosteronism 
were examined. Their clinical characteristics and 
laboratory parameters are presented in Table 1. 
Most of them had a unilateral adrenal abnormal-
ity (62%) on CT scan, while bilateral adrenal thick-
FIGURE 4. Tip of the catheter in the right adrenal vein (arrow); both limbs of the right 
adrenal gland are visible underneath (cone beam CT).
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism 413
ening was present in 10% of the cases. The average 
adrenal nodules’ size was 13 mm and left-sided 
lesions were more prevalent than the right-sided 
ones (62% vs. 38% in total). There were 28 left-sided 
lesions (60%) in the first period and 91 left-sided 
lesions (62%) in the recent period. Finally, in 28% 
of the cases CT scans of both adrenals were consid-
ered normal. 
The average number of AVS procedures per-
formed per year increased statistically significantly 
from 7 in the 2004–2011 period to 29 in the 2012–
2018 period (p < 0.001) (Figure 5). In total, AVS 
had to be repeated in 10% of the procedures (9% 
in the first period, 10% in the recent period). AVS 
was successful (SI ≥ 5 in both adrenal veins) in 86% 
of the patients and in 77% of the procedures. The 
overall success rate of left adrenal vein cannulation 
was significantly higher than that of the right ad-
renal vein (p = 0.001). While the success rate on the 
left side remained unchanged over time (94% vs. 
97%; p = 0.434), there was a statistically significant 
improvement on the right side after the introduc-
tion of a single dedicated interventional radiologist 
in 2012 (66% vs. 94%; p < 0.001). Consequently, the 
proportion of patients with successful AVS (66% vs. 
92%, p < 0.001) and of successful AVS procedures 
(61% vs. 82%, p < 0.001) was also significantly high-
er in the recent period (Figure 6). The right and left 
median SI values were not statistically significant-
ly different (22.3 [interquartile range 18.2] vs. 22.4 
[13.1]; p = 0.285). Decreasing the SI to ≥ 3 instead 
of ≥ 5 would not have improved the AVS perfor-
mance on either side. Among previously tested 
clinical determinants of bilateral AVS success22,23, 
only younger age proved to be statistically signifi-
cant (p = 0.004) in our cohort,  whereas higher BMI 
and male gender did not. Adrenal hemorrhage due 
to vein rupture occurred during two procedures 
(0.8% overall), one in the initial period (1 out of 57 
procedures, 1.8%) and another in the recent peri-
od (1 out of 203 procedures; 0.5%), both resolved 
conservatively. Primary aldosteronism persisted in 
both cases and was treated medically. There were 
no other serious adverse events associated with 
AVS during the study.
CT and AVS results were compared in 181 pa-
tients with bilaterally successful AVS, excluding 
cases with borderline LI values between 3 and 4. 
The agreement amongst the two diagnostic meth-
TABLE 1. Clinical characteristics and laboratory parameters of 
the patients
Characteristic Descriptive statistics
n 235
Male patients 168 (71%)
Age (years) 56 (32–73)
Body Mass Index (kg/m2) 30.4 (18.3–48.4)
Systolic BP at presentation (mm Hg) 155 (145–170)
Diastolic BP at presentation (mm Hg) 90 (80–95)
Number of antihypertensive agents 3 (2–4)
Hypokalemia 172 (73%)
eGFR (ml/min/1.73 m2) 88 (71–102)
Baseline aldosterone (nmol/L) 0.7 (0.3–8.8)
Baseline PRA (ng/mL/h) 0.2 (0.2–0.9)
Baseline ARR 4.2 (1.1–43.8)
CT* normal / bilateral / unilateral
66 (28%) / 
24 (10%) / 
144 (62%)
Tumor size on CT (mm) 13 (8–19)
* = not performed in one patient; ARR = serum aldosterone-to-renin ratio; 
BP = blood pressure; eGFR = estimated glomerular filtration rate; PRA 
= plasma renin activity; Descriptive statistics are reported as median 
(interquartile range) for numeric variables and number (percentage) for 
categorical variables; 
Mean = 7
Mean = 29
0
10
20
30
40
2004 2006 2008 2010 2012 2014 2016 2018
Year
No. of AVS procedures
66%
92%
61%
82%
0% 25% 50% 75% 100%
Patients with successful AVS
2004 - 2011
2012 - 2018
Successful AVS procedures
2004 - 2011
2012 - 2018
FIGURE 6. Patients with successful adrenal vein sampling (AVS) 
and successful AVS procedures during the study period.
FIGURE 5. Number of adrenal vein sampling procedures per 
year during the study period.
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism414
ods was present in only 59% of cases (kappa = 0.36) 
(Figure 7). 
Among the patients with successful AVS, 44% 
overall (n = 79) had LI > 4 and hence proven unilat-
eral disease. The percentage of lateralized cases did 
not statistically significantly differ between the two 
study periods (p = 0.248) or between younger (< 40 
years) and older patients (p = 0.470). Adrenalectomy 
was recommended to all the patients with lateral-
ized aldosterone secretion, but only 86% of them 
underwent surgery. All patients below 40 years of 
age with proven unilateral disease were operated 
on, but the same was true for only 84% of older 
subjects. The main reason for not having surgery 
was patient’s reluctance (n = 9). One patient was 
diagnosed with liver cirrhosis and was rejected by 
the surgeon, two patients were lost to follow-up. 
The proportion of patients with unilateral disease 
undergoing surgery did not differ statistically sig-
nificantly between the periods (89% vs. 85%, p = 
1.000). Finally, additional four out of 21 patients 
with successful AVS and borderline LI values be-
tween 3 and 4 also opted for surgery. Three of them 
had clear unilateral adrenal nodule on CT, whereas 
the remaining patient had normal glands on imag-
ing. All other patients were treated medically.
Discussion
The present study provides an important insight 
in the implementation process and continued de-
velopment of AVS at the Slovenian national endo-
crine referral center over 15 years. The overall suc-
cess rate for the AVS procedures during this period 
was 77%, which is similar to the recently published 
large multicenter AVS registry study on 1625 pa-
tients, where 80% of cases were bilaterally selec-
tive.24 Interestingly, the data from German Conn’s 
Registry revealed that only 31% of their initial AVS 
studies were successful with later increase of the 
success rate to 61%.25 On the other hand, the pro-
portion of successful AVS procedures at our insti-
tution increased from 61% in 2004–2011 to 82% in 
2012–2018. With 10% of procedures being repeated 
overall, the proportion of our patients with suc-
cessful AVS rose concurrently from 66% to 92%, 
which is close to the success rate at the centers of 
excellence.19,26,27 The observed increment could be 
partially explained by our decision in 2012 to fol-
low the recommendation for low-volume centers 
and focus the expertise on a single, dedicated in-
terventional radiologist.12,28 This decision not only 
improved, but also expanded the AVS performance 
at our center (Figure 5). 
 The overall success rate improved due to su-
perior cannulation of the right adrenal vein in the 
recent period (94% vs. 66%), whereas the success 
rate on the left side remained around 95% and un-
changed over time. This was most probably not 
only due to the learning curve of the radiologist29,30, 
but mainly due to more regular pre-procedural 
review of CT images and intra-procedural use of 
high-resolution CBCT since 2012 to better map the 
adrenal venous anatomy, especially on the right 
side. The same approach has been recently used in 
other centers and allowed not only a better evalu-
ation of the selectivity of right-sided adrenal vein 
cannulation, but also a significant decrease in the 
fluoroscopy time and quantity of iodine contrast 
injected in combination with unchanged or even 
lower radiation exposure.13–16 
Recently, another possibility to improve the 
catheterization success has been offered by using 
the newly developed ultra-rapid technique for 
semi-quantitative measurement of the cortisol level 
in adrenal veins in approximately 5 minutes, thus 
enabling the radiologist to reposition the catheter if 
the first result indicates an incorrect position.31 The 
rapid on-site measurement of the cortisol might be 
associated with a shorter procedure time and lower 
radiation dose than CT assisted AVS.32 However, 
this approach was not available at our center dur-
ing the analyzed period.
Throughout the study period we strictly fol-
lowed the Mayo Clinic protocol and used con-
tinuous Synacthen infusion starting 30 min before 
sampling and continuing throughout the proce-
dure during sequential AVS.19 The main rationale 
AVS bilateral AVS left AVS right
CT
bilateral
CT
left
CT
right
51 (28%)
32 (18%)
17 (9%)
6 (3%)
36 (20%)
2 (1%)
14 (8%)
4 (2%)
19 (10%)
100
55%
44
24%
37
20%
71 39%
72 40%
38 21%
N = 181Total
Total
FIGURE 7. Agreement between adrenal vein sampling (AVS) and CT findings 
depicted with a variable-width stacked column chart. Patients with normal CT scans 
are included in the CT bilateral category
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism 415
for ACTH-stimulated AVS is to maximize the cor-
tisol gradient between the adrenal veins and VCI. 
Consequently, SI is increased and so is the propor-
tion of diagnostic AVS procedures, which is why 
such a practice is particularly suitable for less expe-
rienced and low-volume centers.20,21 On the other 
hand, some authors consider the use of ACTH-
stimulation as controversial because it might have 
the undesirable effect of masking the lateralization 
of aldosterone production, thus rendering some 
patients with unilateral primary aldosteronism 
apparently unsuitable for surgery.10 Fortunately, 
accumulated data overall suggest that surgical out-
comes are similar irrespective of whether AVS is 
done by ACTH stimulation or not.5,33,34 
ACTH stimulation also minimizes stress-in-
duced variations in aldosterone secretion during 
sequential sampling19–21, which might otherwise 
generate artificial between-sides gradients and 
lower its diagnostic accuracy.35 Additionally, ac-
cording to our protocol the right adrenal vein was 
always being cannulated first to lessen the time lag 
amid the sides.28 Thereafter, a microcatheter was 
used to quickly cannulate the left adrenal vein36 
and to keep the delay between sequential sampling 
under 5 minutes in most of our AVS procedures.37 
Clearly, AVS studies that are not bilaterally suc-
cessful should not be used to establish lateraliza-
tion.20 The choice of the correct SI is pivotal for the 
reported catheterization success rate, diagnostic 
reliability of the method and clinical outcome.34,38,39 
According to the expert consensus the cutoff value 
for the SI should be ≥ 3.0 during ACTH stimula-
tion20, but we consistently applied an even more 
robust criterion (SI ≥ 5) in order to minimize the 
chance of misdiagnosing either unilateral or bilat-
eral primary aldosteronism.19,21 It is conceivable 
that there is a progressive decrease in success rate 
with increasing SI cut-offs, although the recent 
multicenter study showed this to be less dramatic 
with ACTH-stimulation.34 Concordantly, decreas-
ing the SI to ≥ 3 instead of ≥ 5 in our cohort would 
not improve the cannulation success rate on either 
side. Furthermore, the data from the same study 
showed post-ACTH SI cut-off of 5 to be able to 
clearly segregate biochemically successful and 
non-successful studies.34 Actually, our median 
SI values were much higher than the advocated 
threshold. There was no usual distinction between 
higher median right-sided and lower median left-
sided SI values7,19, pointing to selective cannula-
tion of the left adrenal vein in most cases with the 
microcatheter. Notably, blood sampling from the 
common trunk of the inferior phrenic vein and the 
left adrenal vein might be the preferable method 
of AVS due to better potential diagnostic accuracy, 
technical ease, lower cost and lower risk of vein 
rupture.40 
The overall complication rate during the study 
was low (0.8%). Despite the almost fourfold in-
crease of AVS procedures in the recent period, the 
between periods complication rates were compa-
rable, with one adrenal hemorrhage due to vein 
rupture in each period (1.8% vs. 0.5%). The obser-
vation confirmed that the major determinant of the 
incidence of such events is the number of AVS per-
formed by each radiologist.12
When AVS results were used as the gold stand-
ard for lateralization in a subgroup with unequivo-
cal diagnosis of unilateral (LI > 4) or bilateral (LI 
< 3) disease, CT misdiagnosed the primary aldo-
steronism subtype in 41% of our patients despite 
reassessment of all normal scans at our interdisci-
plinary meetings. If we had relied only on imaging, 
20/71 (28%) patients would have been incorrectly 
denied adrenalectomy and treated medically. 
In addition, 49/100 (49%) patients with bilateral 
primary aldosteronism would have been sent to 
unilateral adrenalectomy, and 6/77 (8%) patients 
with unilateral primary aldosteronism would 
have had removed the normal-functioning adrenal 
(Figure 7). By contrast, Mulatero et al. demonstrat-
ed much higher agreement of AVS and CT (77%) 
when imaging was performed by the same highly 
motivated radiologist.41 Nevertheless, the propor-
tion of discordant AVS and CT results in our co-
hort closely resembles the findings  of a systematic 
review of 38 diagnostic studies on 950 patients, 
where CT (or MRI) might have missed the type of 
primary aldosteronism in 37.8% of cases.8 
Ultimately, 44% of our patients lateralized on 
AVS, which represents a slightly higher prevalence 
of unilateral disease than traditionally reported.4,7 
Yet this finding was not unexpected, because sev-
eral clinical characteristics of our cohort, e.g. high 
median number of antihypertensives, prevalent 
spontaneous hypokalemia and higher median al-
dosterone values, pointed towards more severe 
disease, which is consistent with unilateral pri-
mary aldosteronism. We used the most stringent 
LI cut-off (> 4), which is favored by the expert 
consensus for ACTH-stimulated AVS, in order to 
avoid false-positives and ensure highest possible 
cure rates.10,20,21 Only four out of 21 patients with 
borderline LI values (3–4) were referred to surgery. 
Use of contralateral gland suppression (e.g. lower 
aldosterone to cortisol ratio than the same ratio in 
IVC) might be potentially helpful to determine lat-
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Kocjan T et al. / Adrenal vein sampling for primary aldosteronism416
eralization in intermediate cases8,10,38 but was not 
employed during the study period. Using our con-
servative approach to make surgical decision, close 
to 100% of operated patients at our center achieved 
complete biochemical remission of primary aldo-
steronism according to the international PASO out-
come consensus.5 
Adrenalectomy was recommended to all pa-
tients who lateralized on AVS, however a substan-
tial proportion (14%) was ultimately treated medi-
cally. Only patients older than 40 years changed 
their mind and decided against the operation. 
These outcomes stress the importance of careful 
selection of patients for AVS and operation.28 Most 
appropriate candidates desire surgery and have a 
high probability of unilateral primary aldosteron-
ism. On the other hand, AVS is not needed in indi-
viduals who prefer medical therapy and in those 
who are not suitable for surgery due to comorbidi-
ties or age.21,42 A simple clinical prediction criterion 
could probably identify some patients with bilat-
eral primary aldosteronism who should avoid un-
necessary AVS and be treated medically.18 Last but 
not least, the primary aldosteronism surgical out-
come predictor might help finding patients who 
are expected to attain long-term blood pressure 
control after adrenalectomy to guide preoperative 
patient counseling and final decision for or against 
AVS and surgery.43
There are some limitations of the present study. 
Primarily, the outcomes were deducted from 
a retrospective analysis. However, all relevant 
clinical and laboratory data were logged into our 
AVS database virtually without missing values. 
Furthermore, discontinuation and/or adjustment of 
the antihypertensive agents before and during AVS 
could probably have been more rigorous, especial-
ly during the early years. Still, hypokalemia was al-
ways corrected, mineralocorticoid antagonists and 
potassium-wasting diuretics were discontinued on 
time. Most patients had resistant hypertension, so 
we mostly followed the expert recommendation 
that less interfering antihypertensive medications 
may be used if PRA, which was routinely meas-
ured before AVS, remained suppressed.20,21 ACTH 
stimulation might have the potential to mask lat-
eralization of aldosterone production in patients 
with adenomas simultaneously producing cortisol, 
which appears more frequently than we thought 
earlier.10,44 During the study dexamethasone sup-
pression testing to detect this entity was recom-
mended only in rare patients with relatively large 
adrenal tumors of ≥ 3 cm and not routinely.4,17 
Consequently, another possible source of error 
might have been unrecognized autonomous corti-
sol cosecretion in some patients. Finally, the tech-
nical advances in AVS techniques over the 15-year 
study period and their impact on the AVS success 
rate might not have been emphasized enough.
The main strength of our study is that our results 
were derived from a relatively large and a well-de-
fined national cohort. Management of the patients 
was standardized and followed the Endocrine 
Society clinical guidelines whenever feasible4,17, 
which can significantly decrease the selection bias.
Conclusions 
Based on the present study, we conclude that the 
introduction of a dedicated radiologist with high-
er workload and regular use of intra-procedural 
CBCT since 2012 have significantly enhanced the 
AVS performance at our center. In the future, we 
aim to improve the concordance of AVS results 
with CT findings by revising our interdisciplinary 
strategy with radiologists. We will also address the 
protocols for the selection of appropriate candi-
dates for AVS, since we demonstrated that a sub-
stantial number of patients with proven unilateral 
primary aldosteronism did not proceed to surgery. 
Acknowledgements
The authors would like to thank Marjana Turk 
Jerovsek, M.D. and Barbara Robnik, M.D. for their 
work with the AVS database. We appreciate the 
assistance of Vlasta Hocevar and Mateja Adamlje, 
RNs.
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