Perspectives PAPA
Arterial hypertension is a major cardiovascular risk factor that affects between 10-40% of the population. Primary aldosteronism due to adrenal excess production of aldosterone is the most common curable form of hypertension affecting 4-12% of hypertensives. Given the severe cardiovascular adverse effects of aldosterone excess early detection and individualized treatment of primary aldosteronism has an important impact on clinical outcome and survival. However, the pathophysiology of primary aldosteronism is not well understood: While we recently identified specific genes underlying aldosterone producing adenoma, the most prevalent form of primary aldosteronism, bilateral adrenal hyperplasia, has remained enigmatic.
It is the hypothesis of this ERC proposal that the pathophysiology of primary aldosteronism is a process based on two ‘hits’: agonistic angiotensin II type 1 receptor (AT1R) autoantibodies and somatic mutations. Whereas agonistic autoantibodies induce proliferation and grossly changes adrenal cortex architecture towards diffuse or nodular hyperplasia, somatic mutations result in adenoma formation. Taken together, both factors induce not only aldosterone but also marked glucocorticoid excess.
Interview with Prof. Reincke on the aims of ERC PAPA
News
A user-friendly online tool was developed by Dr. Tracy Williams, Prof. Dr. Martin Reincke and Italian researchers to guide the clinical management of patients with Primary Aldosteronism. The PASO [Primary Aldosteronism Surgical Outcome] predictor was developed to individually advise patients on their likely improvement in hypertension status after adrenalectomy and to facilitate the decision for an operation.
The results were published in peer reviewed journals (Burrello et al. 2019) and non-peer reviewed magazines(https://www.n-tv.de/21028667, http://www.gesundheitsstadt-berlin.de/bluthochdruck-manchmal-heilbar-durch-operation-13320/).
Latest Publications
Yang Y, Reincke M, Williams TA 2019: Treatment of Unilateral PA by Adrenalectomy: Potential Reasons for Incomplete Biochemical Cure. Exp Clin Endocrinol Diabetes. 127, 100-108
Perez-Rivas LG, Williams TA, Reincke M 2019: Inherited Forms of Primary Hyperaldosteronism: New Genes, New Phenotypes and Proposition of A New Classification. Exp Clin Endocrinol Diabetes. 12, 93-99
Reincke M, Beuschlein F, Bornstein F, Eisenhofer G, Fassnacht M, Reisch N, Williams TA 2019: The Adrenal Gland: Central Relay in Health and Disease. Exp Clin Endocrinol Diabetes. 127, 81-83
Burrello J, Burrello A, Stowasser M, Nishikawa T, Quinkler M, Prejbisz A, Lenders JWM, Satoh F, Mulatero P, Reincke M, Williams TA 2019: The Primary Aldosteronism Surgical Outcome Score for the Prediction of Clinical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism. Ann Surg. Jan 2019 [Epub ahead of print]
Yang Y, Burrello J, Burrello A, Eisenhofer G, Peitzsch M, Tetti M, Knösel T, Beuschlein F, Lenders JWM, Mulatero P, Reincke M, Williams TA 2019: Classification of microadenomas in patients with primary aldosteronism by steroid profiling. Steroid Biochem Mol Biol. 189, 274-282
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 H, Widimský J, Hahner S, Douma S, Stowasser M, Mulatero P, Reincke M 2018: Computed Tomography and Adrenal Venous Sampling in the Diagnosis of Unilateral Primary Aldosteronism. Hypertension. 72, 641–649
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 2018: Immunohistopathology and Steroid Profiles Associated With Biochemical Outcomes After Adrenalectomy for Unilateral Primary Aldosteronism. Hypertension. 72, 650–657
Williams TA, Reincke M 2018: MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and Management of Primary Aldosteronism: the Endocrine Society guideline 2016 revisited. Eur J Endocrinol. 179, R19-R29
Reincke M 2018: Anxiety, Depression, and Impaired Quality of Life in Primary Aldosteronism: Why We Shouldn't Ignore It! J Clin Endocrinol Metab. 103, 1-4
Reincke M 2018: Primary Aldosteronism and Cardiovascular Events: It Is Time to Take Guideline Recommendations Seriously. Hypertension. 71, 413-414
Heinze B, Fuss CT, Mulatero P, Beuschlein F, Reincke M, Mustafa M, Schirbel A, Deutschbein T, Williams TA, Rhayem Y, Quinkler M, Rayes N, Monticone S, Wild V, Gomez-Sanchez CE, Reis A-C, Petersenn S, Wester H-J, Kropf S, Fassnacht M, Lang K, Herrmann K, Buck AK, Bluemel C, Hahner S 2018: Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension. 71, 317-325
Aristizabal Prada ET, Castellano I, Sušnik E, Yang Y, Meyer LS, Tetti M, Beuschlein F, Reincke M, Williams TA 2018: Comparative Genomics and Transcriptome Profiling in Primary Aldosteronism. Int. J. Mol. Sci. 19, 1124
Lenders J, Williams TA, Reincke M, Gomez-Sanchez CE, 2018: DIAGNOSIS OF ENDOCRINE DISEASE: 18-Oxocortisol and 18-Hydroxycortisol. Is there clinical utility of these steroids? Eur J Endocrinol., 178, R1-R9
Reincke M, Williams, TA, Beuschlein F, 2017: Diagnosis and Treatment of Primary Aldosteronism in 2017: Did We Achieve Our Goals? Horm Metab Res. 49, 905-907
Lenders J, Eisenhofer G, Reincke M, 2017: Subtyping of Patients with Primary Aldosteronism: An Update. Horm Metab Res. 49, 922-928
Gomez-Sanchez CE, Kuppusamy M, Reincke M, Williams TA, 2017: Disordered CYP11B2 Expression in Primary Aldosteronism. Horm Metab Res. 49, 957-962
Aristizabal Prada ET, Burrello J, Reincke M, Williams TA, 2017: Old and New Concepts in the Molecular Pathogenesis of Primary Aldosteronism. Hypertension. 70, 875-881
Aragao-Santiago L, Gomez-Sanchez CE, Mulatero P, Spyroglou A, Reincke M, Williams TA, 2017: Mouse Models of Primary Aldosteronism: From Physiology to Pathophysiology. Endocrinology. 158, 4129-4138
Williams TA, Lenders J, Mulatero P, Burrello J, Rottenkolber M, Adolf C, Satoh F, Amar L, Quinkler M, Deinum J, Beuschlein F, Kitamoto KK, Pham U, Morimoto R, Umakoshi H, Prejbisz A, Kocjan T, Naruse M, Stowasser M, Nishikawa T, Young WF, Gomez-Sanchez CE, Funder JW, Reincke M, Primary Aldosteronism Surgery Outcome (PASO) investigators, 2017: Outcomes after adrenalectomy for unilateral primary aldosteronism: an international consensus on outcome measures and analysis of remission rates in an international cohort. Lancet Diabetes Endocrinol. 5, 689-699
Arlt W, Lang K, Sitch AJ, Dietz AS, Rhayem Y, Bancos I, Feuchtinger A, Chortis V, Gilligan LC, Ludwig P, Riester A, Asbach E, Hughes BA, O'Neil DM, Bidlingmaier M, Tomlinson JW, Hassan-Smith ZK, Rees DA, Adolf C, Hahner S, Quinkler M, Dekkers T, Deinum J, Biehl M, Keevil BG, Shackleton CHL, Deeks JJ, Walch AK, Beuschlein F, Reincke M, 2017: Steroid metabolome analysis reveals prevalent glucocorticoid excess in primary aldosteronism. JCI Insight. 2, e93136
