The effect of intermittent sampling on aldosterone lateralisation during adrenal venous sampling (AVS) in patients with primary aldosteronism (PA)

In patients with primary aldosteronism (PA) adrenal venous sampling (AVS) is
performed to determine whether there is unilateral or bilateral adrenal
hypersecretion of aldosterone. An accurate distinction between the unilateral
and bilateral type is of utmost importance because patients with the unilateral
type benefit from surgery whereas patients with bilateral PA are treated
medically.
Because it is known that aldosterone secretion is rithmic, many medical
expertise centres give ACTH before the AVS procedure to stimulate aldosterone
secretion. The aim is to increase the accuracy of the procedure by stimulating
aldosterone secretion: ideally, ACTH stimulates aldosterone secretion in the
affected gland and not in the healthy contralateral gland (in unilateral
adrenal pathology), or stimulates aldosterone secretion in both glands (in case
of bilateral hyperplasia). However, a high-dose ACTH might also stimulate
aldosterone production in the healthy contralateral gland which may lead to
misinterpretation of AVS results with negative consequences for the patient;
i.e. withholding surgery from a patient whose clinical situation might improve
after adrenalectomy. In a recent study it was reported that a low-dose ACTH
produced no effect at all. So currently it is unclear whether it is possible to
stimulate only an affected gland by ACTH, and if so, at which ACTH dose.
Therefore, in this research proposal 3 intermittent samples are obtained,
without prior ACTH. It is expected that, despite rithmic secretion, drawing 3
samples will result in at least 1 high result of aldosterone in these 3
samples.
In the regular AVS procedure cortisol concentrations are determined afterwards
to confirm the successful placement of the catheter in the adrenal veins. In
the unfortunate circumstance that cortisol concentration is low in one of the
samples supposed to be obtained from an adrenal vein, the results cannot be
interpreted and a second procedure is necessary. Instantenous measurement of
cortisol during the procedure en recatheterisation in the same procedure if
necessary, can prevent a second procedure.

To study the variability of the lateralisation of the aldosterone/cortisol
ratio*s when 3 instead of 1 sample is obtained and to study whether
instantaneous measurement of cortisol during the procedure will prove to be
advantageous.

This observational study will take place in the University Medical Centre
Nijmegen, St. Radboud.
All patients with proven PA in whom, for diagnostic purposes, AVS is indicated
are asked to participate in the study.
The *study* AVS procedure is different from the *regular* AVS procedure in that
*both adrenal veins are catheterized simultaneously (in stead of sequentially)
*2 extra samples are obtained after 15 and 30 minutes (extending the procedure
with 30 minutes)
*cortisol is measured during in stead of after the catheterization
The study will last for one year, starting in November 2007. During this period
we expect to include approximately 20 patients.

By investigating the difference in lateralisation ratio*s at three different
moments we eventually hope to judge the AVS results more accurately and
reliably select patients eligible for successful adrenalectomy. By analyzing
cortisol during the procedure the patient might benefit whenever a second
procedure is prevented.
The two extra samples will extend the procedure with 30 mintues. The regular
AVS procedure involves a few small risks: i.e. occurrence of hematoma at the
site of the femoral vein, trombosis, complications at the site of the adrenals
and X-ray exposure. Participation in the study implicates that because of
bilateral catheterization there is at both sites of the femoral veins a risk of
hematoma. Besides the, in the regular procedure, minimal risk of trombosis, is
possibly somewhat higher because of the extension of the procedure with
approximately 30 minutes. However, the effect of heparine (which is also
adminstered in the regular procedure) lasts for a few hours.
In the regular and in the study procedure patients are exposed to X-ray
examination for 20 minutes to obtain the first blood sample. Especially for the
study procedure the patient is exposed two times extra (for 5 to 10 seconds) to
X-ray examinations. In comparison to the 'standard' 20 minutes X-ray
examination, this extra time is considered negligible.