A stress reaction affects assessment of selectivity of adrenal venous sampling and of lateralization of aldosterone excess in primary aldosteronism

Abstract

Background: A stress reaction involving increased cortisol release, which has not been documented thus far, might affect the assessment of selectivity of catheterization during adrenal venous sampling (AVS). Objective: To investigate whether an ACTH-driven cortisol release occurs during AVS and whether it influences the assessment of selectivity by the step-up of cortisol (plasma cortisol concentrations, PCC) between the adrenal vein blood (PCC SIDE ) and the inferior vena cava (PCC IVC ), e.g. the selectivity index (SI). Design and methods: We determined the SI in samples obtained simultaneously at starting AVS (t-15) and again after 15 min (t0) in 34 consecutive patients with proven aldosterone-producing adenoma. We then calculated the SI with PCC SIDE obtained at t-15 and at t0, and the PCC IVC values obtained at the different time point, thus simulating sequential AVS. Results: The PCC SIDE and the SI fell significantly from t-15 to t0 on both the sides. When PCC SIDE obtained at t-15 was combined with PCC IVC at t0, the SI values were higher than those obtained with simultaneously drawn samples. This led to label as selective more AVS studies than with bilaterally simultaneous data, especially when using higher cutoffs for the SI. Conclusions: A transient increase in cortisol release from both adrenal glands occurs in the majority of the patients who undergo AVS. This stress reaction can influence the assessment of both the selectivity of the catheterization during the sequential AVS technique and the lateralization of aldosterone excess.

An Expert Consensus Statement on Use of Adrenal Vein Sampling for the Subtyping of Primary Aldosteronism

“…It showed that a stress reaction (1) occurs in most patients when starting AVS; (2) waned rapidly, usually in less than 15 minutes; (3) increases the SI on both sides at the beginning of the procedure; and (4) is likely to influence also the lateralization index (LI) values when using the sequential AVS. 34 Therefore, the authors concluded that simultaneous catheterization should be preferred, and precautions to minimize stress should be systematically exploited. 34 To the latter end, measures to be adopted both before and during AVS entail explanation of the procedure to the patient, reassurance by the doctor and nurses, and use of benzodiazepines and local anesthesia before venipuncture.…”

“…34 Therefore, the authors concluded that simultaneous catheterization should be preferred, and precautions to minimize stress should be systematically exploited. 34 To the latter end, measures to be adopted both before and during AVS entail explanation of the procedure to the patient, reassurance by the doctor and nurses, and use of benzodiazepines and local anesthesia before venipuncture. Allowing the patient to rest quietly for ≥15 minutes before the blood sampling in a friendly environment with psychological assistance can also be useful during the procedure.…”

“…35 PCC values from adrenal venous blood are used for correction of the adrenal aldosterone levels because of inevitable dilution of the samples by nonadrenal blood, even if every effort is made to avoid dilution effects such as blood flow from the accessory hepatic vein and the inferior phrenic vein (see above). 32,33 According to the AVIS, the majority of the large referral centers perform AVS by sequential sampling with cosyntropin stimulation 13 to minimize stress-mediated fluctuations in aldosterone secretion 34,38 and to improve selectivity. 35 Because APAs are heterogeneous in terms of response to adrenocorticotropic hormone, 35,39,51 cosyntropin can exert a confounding effect on aldosterone secretion, thus increasing the risk of misclassification.…”

Primary Aldosteronism: Changing Definitions and New Concepts of Physiology and Pathophysiology Both Inside and Outside the Kidney

“…Because ACTH rises in response to stress, however, aldosterone levels may rise transiently in association with apprehension, discomfort, or other stressful stimuli, and this may contribute towards an apparent response to upright posture, or prevent suppression during saline loading. Stress-induced rises in ACTH can cause aldosterone to rise at the start of a procedure such as adrenal venous sampling (AVS), only to fall into a trough during sample collection (463). This may explain some of the occasional instances where the AVS study is unsatisfactory because of the apparent lack of secretion by either gland at the time of sampling (571).…”

Update in diagnosis and management of primary aldosteronism

“…In fact, the simultaneous catheterization of adrenal veins was proven to provide more reliable results, since more than a half of the patients undergoing AVS present an ACTH-induced stress response, causing an increased cortisol release, which may lead to misinterpretation of the selectivity index when sequential catheterization is used [60].…”