Adrenocorticotropic Hormone–Stimulated Adrenal Venous Sampling Underestimates Surgically Curable Primary Aldosteronism: A Retrospective Cohort Study and Review of Contemporary Studies

Abstract

Guidelines recommend adrenal venous sampling to determine disease laterality in primary aldosteronism. Adrenocorticotropic hormone (ACTH) stimulation clearly improves the likelihood of successful adrenal vein catheterization but may lead to a decrease in lateralization rates. To examine the impact of ACTH on lateralization, we performed a retrospective analysis of 340 patients with confirmed primary aldosteronism who underwent adrenal venous sampling with a single interventional radiology team using a protocol of sampling both before and after an ACTH bolus. In addition to this original research, we conducted a review of similar studies from the past 5 years to develop a consensus on the impact of ACTH on lateralization for primary aldosteronism. In the original research analysis, following a bolus of ACTH, 58% of patients had a decline in lateralization index which led to discordance between the pre-ACTH and post-ACTH classifications of lateralization in up to 26% of cases. The majority of discordant cases were due to reclassification from unilateral disease pre-ACTH to bilateral disease post-ACTH. In patients who already lateralized with unstimulated sampling, the response to ACTH did not have any impact on surgical outcomes. In a review of contemporary studies, we identified 11 similar studies in the past 5 years, of which 10 reported either no change or a decrease in lateralization index following ACTH, resulting in ≈25% discordance between unstimulated and stimulated lateralization rates. We conclude that ACTH stimulation during adrenal venous sampling can underestimate surgically remediable primary aldosteronism and recommend that the role of ACTH be limited primarily to enhancing selectivity.

11C-Metomidate PET-CT versus adrenal vein sampling to subtype primary aldosteronism: a prospective clinical trial

“…Asymmetrical aldosterone overproduction may occur in bilateral primary aldosteronism, and possibly explain failure of biochemical cure after unilateral adrenalectomy [20]. Recent data suggest that cosyntropin reduces lateralization index, and hence identifies fewer patients with unilateral primary aldosteronism [21,22]. This was also observed in a few of our patients whereby the initial AVS with cosyntropin showed bilateral primary aldosteronism, but repeat AVS without cosyntropin indicated unilateral primary aldosteronism.…”

“…Asymmetrical aldosterone overproduction may occur in bilateral primary aldosteronism, and possibly explain failure of biochemical cure after unilateral adrenalectomy [20]. Recent data suggest that cosyntropin reduces lateralization index, and hence identifies fewer patients with unilateral primary aldosteronism [21,22]. This was also Adjusted by Bonferroni comparison [18].…”

Role of Adrenal Vein Sampling in Guiding Surgical Decision in Primary Aldosteronism

“…Meanwhile, the effect of ACTH on LR is variable in the literature, with possibly a general tendency to a decreased LR following ACTH administration compared to baseline [19,54,[56][57][58]. One study, however, found a tendency to increased ACTH-stimulated LR [59].…”

“…This discordance varies greatly between studies, from around 9 % [59,60] up to 41 % [61]. In their review of the last 12 studies, Yozamp et al estimated the discordance in lateralization to be around 26 % [56]. In many cases, the discordance was driven by a loss of lateralization following ACTH administration (i. e., lateralized-tobilateral) [11, 19, 21, 47, 54, 56-58, 61, 62].…”

The Entity of Connshing Syndrome: Primary Aldosteronism with Autonomous Cortisol Secretion

“…Similarly, ACTH stimulation during AVC might provide some help, but it is not routinely indicated [ 111 , 112 ]. The rationale of this test (used in 40% of centres, but not with guideline indication) is to maximize cortisol secretion to avoid the daily pulsatile pattern [ 113 , 114 ].…”