Examining aldosterone plasma concentration alterations post-ACTH stimulation in healthy subjects: a systematic literature review and meta-analysis on ACTH's role in aldosterone secretion.

Purpose: Adrenocorticotropic hormone (ACTH), in addition to the renin-angiotensin-aldosterone axis, is a potent aldosterone stimulator, suggesting a potential contribution to conditions associated with increased ACTH concentrations. This study aims to systematically review and synthesize the scientific evidence of alterations of plasma aldosterone concentrations in response to ACTH stimulation during the cosyntropin (Synacthen) test and define the range of aldosterone response.

Methods: A systematic search of PubMed, Medline, and Google Scholar databases according to PRISMA guidelines was performed. Only studies that assessed the alterations in plasma aldosterone concentrations following ACTH stimulation in healthy individuals were included. We incorporated studies that utilized the doses of 1 μg, 250 μg, 0.125 μg/m², or 0.5 μg/m² of ACTH. Out of 1599 initially assessed articles, 17 were deemed relevant to our research. The selected articles were assessed by two independent investigators based on the predetermined inclusion and exclusion criteria. Finally, eight full-text articles were included.

Results: The analyzed studies revealed a significant increase in plasma aldosterone concentrations in healthy subjects after ACTH stimulation, irrespective of the ACTH dose. The peak aldosterone concentration after the 250 μg dose occurred at 30 min, whereas smaller doses exhibited an earlier peak, at around 15 min. On average, plasma aldosterone concentration increased by 125.5% after the 1 μg and 0.5 μg/m² doses, and by 189.6% after 250 μg.

Conclusion: The presented evidence strongly supports the contribution of ACTH to aldosterone secretion regulation beyond the renin-angiotensin-aldosterone axis. Establishing a normal aldosterone response threshold following standardized ACTH stimulation could aid in identifying individuals with ACTH-dependent aldosterone hypersecretion and guide personalized and effective treatment strategies.