Primary aldosteronism: pathogenesis and advanced approaches for subtyping

Hauptforscher:innen

Scientific Staff

Lucie Meyer – Postdoc

Project Description

Project B15 is about primary aldosteronism which is characterized by excessive secretion of aldosterone mainly due to an unilateral adenoma (APA) or bilateral adrenal hyperplasia (BAH). Since the pathogenesis of BAH remains obscure, this project will define pathogenetic mechanisms causing BAH by delineating the molecular histopathological differences between normal adrenals, BAH and APA. In addition, this project will establish new diagnostic markers (venous steroid profiling) for primary aldosteronism and for stratification of the subtypes APA and BAH.

Aims

(I) Identify molecular determinants of the pathogenesis of bilateral adrenal hyperplasia (BAH).

(II) Establish a peripheral venous steroid signature that classifies primary aldosteronism genotype and identify an association between steroid profiling and molecular morphology.

(III) Prospectively validate peripheral venous steroid biomarker panels for the diagnosis and differentiation of unilateral aldosterone-producing adenoma (APA) and BAH.

PhD/MD-Thesis

Yuhong Yang (2017-2021)Title of thesis: Micro- and macro-aldosterone-producing adenomas in primary aldosteronism: molecular and biochemical studies

Lucie Meyer (2017-2021)Title of thesis: Pathophysiology of primary aldosteronism: adrenal immunohistochemistry and molecular profiling studies

Publications

2020
1- Williams TA, Gomez-Sanchez CE, Rainey WE, Giordano TJ, Lam AK, Marker A, Mete O, Yamazaki Y, Zerbini MCN, Beuschlein F, Satoh F, Burrello J, Schneider H, Lenders JWM, Mulatero P, Castellano I, Knösel T, Papotti M, Saeger W, Sasano H, Reincke M. International Histopathology Consensus for Unilateral Primary Aldosteronism. J Clin Endocrinol Metab. 2021 Jan 1;106(1):42-54. doi: 10.1210/clinem/dgaa484. PMID: 32717746

2- Vohra T, Kemter E, Sun N, Dobenecker B, Hinrichs A, Burrello J, Gomez-Sanchez EP, Gomez-Sanchez CE, Wang J, Kinker IS, Teupser D, Fischer K, Schnieke A, Peitzsch M, Eisenhofer G, Walch A, Reincke M, Wolf E, Williams TA. Effect of Dietary Sodium Modulation on Pig Adrenal Steroidogenesis and Transcriptome Profiles. Hypertension. 2020 Dec;76(6):1769-1777. doi: 10.1161/HYPERTENSIONAHA.120.15998. Epub 2020 Oct 19. PMID: 33070662

3- Burrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, Lenders JWM, Satoh F, Mulatero P, Reincke M, Williams TA. The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism. Ann Surg. 2020 Dec;272(6):1125-1132. doi: 10.1097/SLA.0000000000003200. PMID: 30672800

4- Eisenhofer G, Durán C, Cannistraci CV, Peitzsch M, Williams TA, Riester A, Burrello J, Buffolo F, Prejbisz A, Beuschlein F, Januszewicz A, Mulatero P, Lenders JWM, Reincke M. Use of Steroid Profiling Combined With Machine Learning for Identification and Subtype Classification in Primary Aldosteronism. JAMA Netw Open. 2020 Sep 1;3(9):e2016209. doi: 10.1001/jamanetworkopen.2020.16209. PMID: 32990741

5- Sun N, Meyer LS, Feuchtinger A, Kunzke T, Knösel T, Reincke M, Walch A, Williams TA. Mass Spectrometry Imaging Establishes 2 Distinct Metabolic Phenotypes of Aldosterone-Producing Cell Clusters in Primary Aldosteronism. Hypertension. 2020 Mar;75(3):634-644. doi: 10.1161/HYPERTENSIONAHA.119.14041. Epub 2020 Jan 20. PMID: 31957522

2018
1- Meyer LS, Wang X, Sušnik E, Burrello J, Burrello A, Castellano I, Eisenhofer G, Fallo F, Kline GA, Knösel T, Kocjan T, Lenders JWM, Mulatero P, Naruse M, Nishikawa T, Peitzsch M, Rump LC, Beuschlein F, Hahner S, Gomez-Sanchez CE, Reincke M, Williams TA. Immunohistopathology and steroid profiles associated with biochemical outcomes after adrenalectomy for unilateral primary aldosteronism. Hypertension 2018; In press

2- Williams TA, Burrello J, Sechi LA, Fardella CE, Matrozova J, Adolf C, Baudrand R, Bernardi S, Beuschlein F, Catena C, Doumas M, Fallo F, Giacchetti G, Heinrich DA, Saint-Hilary G, Jansen PM, Januszewicz A, Kocjan T, Nishikawa T, Quinkler M, Satoh F, Umakoshi N, Widimský Jr J, Hahner S, Douma S, Stowasser M, Mulatero P, Reincke M. Computed tomography and adrenal venous sampling in the diagnosis of unilateral primary aldosteronism. Hypertension 2018; In press

3- Williams TA and Reincke M. Diagnosis and Management of Primary Aldosteronism: the Endocrine Society guideline 2016 revisited Eur J Endocrinol. 2018;179(1):R19-R29 Invited

4- Aristizabal Prada ET, Castellano I, Sušnik E, Yang Y, Meyer LS, Tetti M, Beuschlein F, Reincke M, Williams TA Functional genomics and genetics of sporadic aldosterone producing adenomas. Int. J. Mol. Sci. 2018;19(4).pii:E1124.

5- Lenders JWM, Williams TA, Reincke M, Gomez-Sanchez CE. DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-Hydroxycortisol. Is there clinical utility of these steroids? Eur J Endocrinol. 2018;178:R1-R9.

2017
6- Santiago LA, Gomez-Sanchez CA, Mulatero P, Spyroglou A, Reincke M, Williams TA. Mouse models of primary aldosteronism: from physiology to pathophysiology. Endocrinology 2017;158:4129–4138.

7- Lenders JWM, Eisenhofer G, Reincke M. Subtyping of Patients with Primary Aldosteronism: An Update. Horm Metab Res. 2017;49:922-928.

8- Gomez-Sanchez CE, Kuppusamy M, Reincke M and Williams TA. Disordered CYP11B2 expression in Primary Aldosteronism. Horm Metab Res. 2017;49:957-962.

9- Reincke M, Williams TA, Beuschlein F. Diagnosis and Treatment of Primary Aldosteronism in 2017: Did We Achieve Our Goals? Horm Metab Res. 2017;49: 905- 907.

10- Prada ETA, Burrello J, Reincke M, Williams TA. Old and new concepts in the molecular pathogenesis of primary aldosteronism. Hypertension 2017;70:875-881.