Progress in Primary Aldosteronism 7: No better time to meet!

Key words

aldosterone - renin - adrenal adenoma - secondary hypertension - endocrine hypertension

Introduction

Fourteen years ago, in July 2009, we held the first Progress in Primary Aldosteronism (PIPA) meeting in Munich. Our idea was that a meeting dedicated to primary aldosteronism (PA) would facilitate collaborative research and scientific exchange in the field. Since then, five more PIPA meetings in 2011, 2013, 2015, 2017 and 2019 gathered scientists from around the world and led to the Progress in Primary Aldosteronism special issues in Hormone and Metabolic Research (2011, 2015, 2017, 2020) and in the European Journal of Endocrinology (2013) that covered current knowledge by PIPA participants. Also, numerous collaborative projects were initiated at these conferences.

Then, in 2020, the COVID-19 outbreak caused an unprecedented challenge to humanity, science and research. Worldwide public and private initiatives were undertaken to fight the pandemic, and for 2 long years, everyone was stuck in a black hole. Research related to the COVID-19 emergency increased dramatically, and increasing resources were directed towards pandemic-related research areas. Research in many fields, not directly related to the pandemic, suffered or was partially displaced [1]. Due to the pandemic, we were unable to hold our biennial PIPA meeting in 2021.

The Pipa 7 Conference In Munich 2022

Following the recovery in 2022, we believed that the ideal time had come to reconvene. Major progress had been made during the past years, and key publications have addressed new genetic events [2] [3] [4] [5] [6] [7], diagnosis [8, 9] pathophysiology of aldosterone excess [10] [11] [12] [13] [14] [15], imaging [16], histopathologic classifications [17], and treatment [18] but unresolved and controversial issues remain. In October 2022, PIPA 7 took place in the usual location at Castle Nymphenburg in Munich. With the generous support of the Deutsche Forschungsgemeinschaft and the Carl Friedrich von Siemens Stiftung we were able to invite many of the internationally renowned researchers in the field [Fig. 1]. The present volume of Experimental and Clinical Endocrinology and Diabetes is entirely dedicated to reviews based on PIPA 7 presentations. To avoid overlap with prior PIPA proceedings the current reviews focus on areas, which can be considered as ‘hot topics’ or those which have not been recently covered. They are written by experts in their respective fields and include seven invited articles summarizing main presentations given at the symposium.

The first article by Celso and Elisa Gomez-Sanchez presents an abbreviated history of aldosterone metabolism, including the most relevant mineralocorticoid steroids implicated in PA [19].

Primary aldosteronism is characterized by dysregulated, renin-independent aldosterone excess. Long perceived as rare, PA has emerged as one of the most common causes of secondary hypertension. The first review by Charoensri & Turcu summarize the reports on PA prevalence among the general population and in specific high-risk subgroups, highlighting the impact of rigid versus permissive criteria on PA prevalence perception [20].

Despite the well-established data on prevalence of PA, the current rate of PA detection is appallingly low. The review by Libianto et al. explores the challenges that clinicians often face in diagnosing PA and offers strategies that may improve the detection of this potentially curable form of hypertension [21].

Lenzini et al. review the current knowledge of the factors that contribute to the resistant hypertension phenotype with a focus on PA and discuss the issues regarding the screening for PA in this setting and the therapeutic approaches [22].

The article of Younes et al. analyses the role of different selectivity and lateralization indices during adrenal vein sampling on guiding surgical decision towards adrenalectomy in primary aldosteronism [23]. Current clinical guidelines recommend that adrenal vein sampling may not be necessary in patients younger than 35 years who have marked aldosteronism and a solitary adrenal adenoma on imaging. The review by Gkaniatsa & Ragnarsson evaluates the more recent literature about imaging studies in young patients as a predictor of unilateral PA [24].

Finally, the review by Lee & Drake summarizes current evidence concerning radio frequency ablation of unilateral aldosterone-producing lesions as an alternative to unilateral adrenalectomy [25].

We hope our readers find these articles interesting.

Fig. 1 Participants of PIPA 7 in the Carl Friedrich von Siemens Foundation in Nymphenburg, Munich. Source: Martin Reincke.

Martin Reincke

Editor-in-Chief

Experimental and clinical Endocrinology and Diabetes

William E. Rainey

Tracy Ann Williams

Conflict of Interest

The authors declare that they have no conflict of interest.

• References

• 1 Riccaboni M, Verginer L. The impact of the COVID-19 pandemic on scientific research in the life sciences. PLoS One 2022; 17: e0263001 DOI: 10.1371/journal.pone.0263001.. eCollection 2022.
• 2 Scholl UI, Stölting G, Schewe J et al. CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet 2018; 50: 349–354. 10.1038/s41588-018-0048-5. Epub 2018 Feb 5.
• 3 Fernandes-Rosa FL, Daniil G, Orozco IJ et al. A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism. Nat Genet. 2018; 50: 355–361. 10.1038/s41588-018-0053-8. Epub 2018 Feb 5. PMID: 29403012 Free article.
• 4 Zhou J, Azizan EAB, Cabrera CP et al. Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nat Genet. 2021; 53: 1360–1372. 10.1038/s41588-021-00906-y. Epub 2021 Aug 12. PMID: 34385710 Free PMC article.
• 5 Le Floch E, Cosentino T, Larsen CK et al. Identification of risk loci for primary aldosteronism in genome-wide association studies. Nat Commun. 2022; 13: 5198. 10.1038/s41467-022-32896-8. PMID: 36057693 Free PMC article.
• 6 Naito T, Inoue K, Sonehara K et al. Genetic risk of primary aldosteronism and Its contribution to hypertension: a cross-ancestry meta-analysis of genome-wide association studies. Circulation. 2023; 147: 1097-1109. 10.1161/CIRCULATIONAHA.122.062349. Epub 2023 Feb 21. PMID: 36802911 Free PMC article.
• 7 Wu X, Azizan EAB, Goodchild E et al. Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production. Nat Genet. 2023; 55: 1009–1021. 10.1038/s41588-023-01403-0. Epub 2023 Jun 8. PMID: 37291193 Free PMC article.
• 8 Brown JM, Siddiqui M, Calhoun DA et al. The unrecognized prevalence of primary aldosteronism: a cross-sectional study. Ann Intern Med. 2020; 173: 10–20. 10.7326/M20-0065. Epub 2020 May 26. PMID: 32449886 Free PMC article.
• 9 Eisenhofer G, Kurlbaum M, Peitzsch M et al. The saline infusion test for primary aldosteronism: implications of immunoassay inaccuracy. J Clin Endocrinol Metab. 2022; 107: e2027–e2036. 10.1210/clinem/dgab924. PMID: 34963138 Free PMC article.
• 10 Nanba K, Omata K, Gomez-Sanchez CE et al. Genetic characteristics of aldosterone-producing adenomas in blacks. Hypertension. 2019; 73: 885–892. 10.1161/HYPERTENSIONAHA.118.12070. PMID: 30739536 Free PMC article.
• 11 Taylor MJ, Ullenbruch MR, Frucci EC. et al. Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation. J Clin Invest 2020; 130: 83-93 DOI: 10.1172/JCI127429.
• 12 Wannachalee T, Caoili E, Nanba K et al. The concordance between imaging and adrenal vein sampling varies with aldosterone-driver somatic mutation. J Clin Endocrinol Metab. 2020; 105: e3628–e3637. 10.1210/clinem/dgaa482. PMID: 32717082 Free PMC article.
• 13 Gong S, Sun N, Meyer LS et al. Primary aldosteronism: spatial multiomics mapping of Genotype-Dependent Heterogeneity and Tumor Expansion of Aldosterone-Producing gdenomas. Hypertension. 2023; 80: 1555–1567. 10.1161/HYPERTENSIONAHA.123.20921. Epub 2023 May 1. PMID: 37125608
• 14 Nanba K, Baker JE, Blinder AR et al. Histopathology and genetic causes of primary aldosteronism in young adults. J Clin Endocrinol Metab 2022; 107: 2473–2482. 10.1210/clinem/dgac408. PMID: 35779252 Free PMC article.
• 15 Turcu AF, Yang J, Vaidya A Primary aldosteronism – a multidimensional syndrome. Nat Rev Endocrinol 2022; 18: 665–682. 10.1038/s41574-022-00730-2. Epub 2022 Aug 31. PMID: 36045149 Review.
• 16 Wu X, Senanayake R, Goodchild E et al. [11C]Metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial. Nat Med. 2023; 29: 190–202. 10.1038/s41591-022-02114-5. Epub 2023 Jan 16.
• 17 Williams TA, Gomez-Sanchez CE, Rainey WE et al. International histopathology consensus for unilateral primary aldosteronism. J Clin Endocrinol Metab. 2021; 106: 42–54. 10.1210/clinem/dgaa484. PMID: 32717746 Free PMC article.
• 18 Williams TA, Gong S, Tsurutani Y et al. Adrenal surgery for bilateral primary aldosteronism: an international retrospective cohort study. Lancet Diabetes Endocrinol. 2022; 10: 769–771. 10.1016/S2213-8587(22)00253-4. Epub 2022 Sep 19.
• 19 Gomez-Sanchez CE, Gomez-Sanchez EP. An abbreviated history of aldosterone metabolism: current and future challenges. Exp Clin Endocrinol Diabetes 2023; DOI: 10.1055/a-2054-1062.. Online ahead of print. PMID: 36918165
• 20 Charoensri S, Turcu AF. Primary aldosteronism prevalence – an unfolding story. Exp Clin Endocrinol Diabetes 2023; DOI: 10.1055/a-2066-2696.. Online ahead of print. PMID: 36996879
• 21 Libianto R, Stowasser M, Russell G et al. Improving detection rates for primary aldosteronism. Exp Clin Endocrinol Diabetes. 2023. 10.1055/a-2048-6213. Online ahead of print. PMID: 37160153
• 22 Lenzini L, Pintus G, Rossitto G et al. Primary aldosteronism and drug resistant hypertension: a "chicken-egg" story. Exp Clin Endocrinol Diabetes. 2023. 10.1055/a-2073-3202. Online ahead of print. PMID: 37054985
• 23 Younes N, Larose S, Bourdeau I. et al. Role of adrenal vein sampling in guiding surgical decision in primary aldosteronism. Exp Clin Endocrinol Diabetes 2023; 131: 418–434.
• 24 Gkaniatsa E, Ragnarsson O. Adrenal vein sampling in the young - necessary or not?. Exp Clin Endocrinol Diabetes 2023; 131: 435–437 DOI: 10.1055/a-2099-3525.. Online ahead of print . PMID: 37225137
• 25 Lee YN, Drake WM. Radiofrequency ablation in primary aldosteronism. Exp Clin Endocrinol Diabetes 2023; 131: 438–442.

Publication History

Article published online:
11 August 2023