Macrolide-Induced Aldosterone Suppression as a Functional Marker of KCNJ5-Mutated Aldosterone-Producing Adenoma: A Proof-of-Concept Clinical and Experimental Study (MAPA Study)
Clicks: 3
ID: 326590
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Emerging Content
0.6
/100
3 views
2 readers
AI Quality Assessment
Not analyzed
Readership in this journal
EmergingRanked #84 of 96 articles by views in european journal of endocrinology
Most read
Least read
Bar heights use a square-root scale.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
OBJECTIVE: Primary aldosteronism (PA), the most common curable form of hypertension, is frequently caused by aldosterone-producing adenomas (APAs) harboring KCNJ5 mutations that render aldosterone synthesis sensitive to macrolides in vitro. This study aimed to evaluate whether a single dose of roxithromycin reduces plasma aldosterone concentration (PAC) and blood pressure (BP) in patients with KCNJ5-mutated APA, and to characterize the haemodynamic effects of macrolides in mice. DESIGN: Prospective, within-patient pharmacologic challenge. METHODS: At the specialized Hypertension Center, University of Padua, eligible consecutive hypertensive patients screened for PA underwent a pharmacologic challenge with a single oral dose of roxithromycin to investigate the within-patient changes in plasma aldosterone concentration (PAC), active renin, cortisol, and blood pressure (BP). RESULTS: Among 373 challenged patients, 18 had KCNJ5 (G151R or L168R) -mutated APA, 25 had wild-type APA, and 307 had no PA. Roxithromycin reduced PAC (P<0.001) only in APA with KCNJ5 mutation, albeit it did not lower BP values. However, it produced a small BP decrease in non-PA hypertensive patients. Mouse studies showed that this BP-lowering can be due to macrolides-induced attenuation of angiotensin II actions and enhancement of endothelium- and nitric oxide-dependent vasodilation. CONCLUSIONS: The selective suppression of aldosterone secretion with roxithromycin in KCNJ5-mutated APA in vivo, which aligns with ex-vivo mechanistic data, can represent a functional marker of KCNJ5 mutations and could help guide precision subtyping of PA patients. Macrolides also exhibit an aldosterone-independent antihypertensive effect in non-PA patients, which involves nitric oxide-dependent vasodilation.
| Reference Key |
openalex_W7204552549
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Gian Paolo Rossi, Brasilina Caroccia, Alessandro Bressan, Clement Byiringiro, Ana M. Briones, Giulio Ceolotto, Giuseppe Zanotti, Roberto Padrini, Ana Maria Briones, Teresa Maria Seccia |
| Journal | european journal of endocrinology |
| Year | 2026 |
| DOI |
10.1093/ejendo/lvag161
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.