Background.
ACTH stimulation was proposed to overcome the potential biases associated with pulsatile aldosterone secretion during AVS. Different protocols and doses of synthetic ACTH have been used but no systematic comparison between them was available.
Aim.
To compare the effects of 3 different doses of ACTH on the selectivity (SI) and the lateralization index (LI).
Patients and Methods.
We prospectively tested the effect of a high dose (HD; 250 μg as an i.v. bolus, n=41), a very low dose (VLD, 250 pg as an i.v. bolus followed by 0.5 pg/min infusion, n=6) and an intermediate dose (ID 50 μg/hr; n=7) on the SI and LI in patient referred for primary aldosteronism. Blood sampling for the measurement of plasma aldosterone (PAC) and cortisol (PCC) concentration were obtained at baseline and 30 minutes after ACTH stimulation, using bilaterally simultaneous AVS. The SI was calculated as the ratio between cortisol levels in the right (C
RAV
) or left (C
LAV
) adrenal vein and the infrarenal inferior vena cava (C
IVC
); the LI was assessed as the ratio of aldosterone to cortisol on the side with the higher ratio (A/C
SIDE
) over the contralateral aldosterone to cortisol (A/C
CTRL
). The diagnosis of APA was based on pathology and follow-up data.
Results.
The HD induced a highly significant increase of PCC in IVC (+83%, P<0.003) and on the SI on both sides (SI
RIGHT
+120%; SI
LEFT
+122%, P<0.001), as compared to baseline values. By contrast, no significant change of PCC in IVC and of the SI was seen with the VLD. The ID elicited a significant increase of PCC in the infrarenal IVC (+82%, P<0.001), which was not significantly different from that seen with the HD. Likewise, the ID increased the SI (SI
RIGHT
+177%, P<0.001; SI
LEFT
+ 727%, P<0.001). In the patients with an unequivocal diagnosis or APA based on the ‘four corners’ criteria, the HD and the ID led to wrong identification of the APA side in 28 and 25%, respectively.
Conclusions.
The HD and the ID improve the ascertainment of the selectivity of adrenal vein catheterization during AVS; by contrast, no significant effect of the VLD on either PAC or PCC was seen. The improvement in the assessment of selectivity with both the HD and the ID should be weighed against the confounding effect on correct identification of lateralized aldosterone excess to the APA side.
Identification of subsets of Aldosterone-Producing Adenoma (APA) with dynamic Adrenal Vein Sampling (AVS)