Table 4.

Summary of recent AVS studies comparing stimulated and unstimulated lateralization indices (LI).

	Patient characteristics	Type of study	AVS procedure	Finding
Yozamp et al, 2021	340 patients	Retrospective cohort	- Simultaneous sampling - ACTH bolus	- LI decreased in 58% after ACTH - Most discordance driven by Unilateral-to-Bilateral group after ACTH - Concordant unilateral group had more biochemically severe disease - Response to ACTH not associated with improved outcomes
Sung et al, 2020³¹	76 patients, all of whom had adrenalectomy	Retrospective cohort	- Simultaneous sampling - ACTH bolus followed by infusion	- Mean LI increased with ACTH - 9.2% in Unilateral-to-Bilateral group after ACTH (using LI cut-off of 4 for both)
Chee et al, 2020¹⁸	201 patients	Retrospective	- Sequential sampling - ACTH bolus followed by infusion	- Significant decrease in LI after ACTH - Lateralization rates decreased with ACTH (70% vs 54% using LI cut-offs of 3 pre- and 4 post-ACTH)
Yatabe et al, 2020²¹	185 patients, 81 of whom had adrenalectomy for unilateral disease	Retrospective	- Sequential sampling - ACTH bolus only	- Significant decrease in LI after ACTH - Lateralization rates decreased after ACTH (72% pre vs 36% post using LI cut-offs of 2 and 2.6 respectively) - Post-ACTH LI correlated better with postop blood pressure
Kobayashi et al, 2020³⁶	1854 patients, 314 of whom underwent adrenalectomy	Retrospective cohort	- Sequential sampling - ACTH bolus only, bolus + infusion, or infusion only	- Lateralization discordance rates of 40% in total cohort and 22% in adrenalectomy cohort, driven by Unilateral-to-Bilateral (U to B) group after ACTH - U to B group had poorer outcomes compared to consistent unilateral group
Rossitto et al, 2020²²	1625 individual AVS studies across 19 centers; 402 patients had both stimulated and unstimulated AVS	Retrospective	- Roughly half of centers with sequential sampling, half with simultaneous - ACTH infusion	- ACTH reduced LI and lateralization rates - Post-adrenalectomy outcomes not improved by ACTH
Violari et al, 2019⁴²	32 patients, all of whom had adrenalectomy	Retrospective	- ACTH bolus followed by infusion	- 22% lateralized pre-ACTH but not post-ACTH (using LI cut-offs of 4 for both)
Wannachalee et al, 2019²⁰	222 patients	Retrospective	- Simultaneous - ACTH bolus only	- LI increased in 27%, decreased in 33%, and remained stable in 40% after ACTH - Discordant lateralization in 24% of cases, driven by U to B group and those with milder disease - KCNJ5 mutations associated with decreasing LI after ACTH - ATP1A1 and ATP2B3 mutations associated with increasing LI
Takeda et al, 2019²⁶	1425 patients with successful AVS from 28 sites	Retrospective	- Varied	- Decrease in lateralization rates (62% pre vs 28% post, using cut-offs of 2 and 4) - ACTH did not contribute to better outcomes
Laurent et al, 2018¹⁶	14 studies	Meta-analysis	- Varied	- AVS with ACTH did not change lateralization
El Ghorayeb et al, 2016¹⁹	171 successful AVS procedures	Retrospective cohort	- Simultaneous - ACTH bolus only	- Discordant lateralization in 28%, mostly U to B group after ACTH - LI decreased in 53%; median LI 7 pre-ACTH vs 6.7 post-ACTH
Wolley et al, 2016³⁵	47 AVS procedures	Retrospective	- Sequential - ACTH bolus only	- 9% discordance rate pre- and post-ACTH