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Treatment of Primary Aldosteronism with mTORC1 Inhibitors

Trinh, Beckey and Hepprich, Matthias and Betz, Matthias J. and Burkard, Thilo and Cavelti-Weder, Claudia and Seelig, Eleonora and Meienberg, Fabian and Kratschmar, Denise V. and Beuschlein, Felix and Reincke, Martin and Odermatt, Alex and Hall, Michael N. and Donath, Marc Y. and Swierczynska, Marta M.. (2019) Treatment of Primary Aldosteronism with mTORC1 Inhibitors. Journal of Clinical Endocrinology and Metabolism, 104 (10). pp. 4703-4714.

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Official URL: https://edoc.unibas.ch/74198/

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Abstract

mTORC1 activity is often increased in the adrenal cortex of patients with primary aldosteronism and mTORC1 inhibition decreases aldosterone production in adrenocortical cells, suggesting the mTORC1 pathway as a possible target for treatment of primary aldosteronism.; To investigate the effect of mTORC1 inhibition on adrenal steroid hormones and hemodynamic parameters in mice and in patients with primary aldosteronism.; (i) Plasma aldosterone, corticosterone and angiotensin II were measured in mice treated for 24 hours with vehicle or rapamycin. (ii) Plasma aldosterone levels after a saline infusion test, plasma renin, 24-hour urine steroid hormone metabolome and hemodynamic parameters were measured during an open-label study in 12 patients with primary aldosteronism before and after two-weeks of treatment with everolimus and after a two-week washout period.; (i) Change in plasma aldosterone levels. (ii) Change in other steroid hormones, renin, angiotensin II and hemodynamic parameters.; Treatment of mice with rapamycin significantly decreased plasma aldosterone levels (P = 0.007). Overall, treatment of primary aldosteronism patients with everolimus significantly decreased blood pressure (P < 0.05) and increased renin levels (P = 0.001) but did not lead to a significant reduction in aldosterone levels. However, prominent reduction of aldosterone levels upon everolimus treatment was observed in 4 out of 12 patients.; In mice, mTORC1 inhibition was associated with reduced plasma aldosterone levels. In patients with primary aldosteronism, mTORC1 inhibition was associated with improved blood pressure and renin suppression. In addition, mTORC1 inhibition appeared to reduce plasma aldosterone in a subset of patients.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Molecular and Systems Toxicology (Odermatt)
UniBasel Contributors:Odermatt, Alex and Trinh, Beckey and Betz, Matthias Johannes Maximilian and Hepprich, Matthias and Burkard, Thilo and Cavelti-Weder, Claudia and Seelig, Eleonora and Meienberg, Fabian and Kratschmar, Denise and Hall, Michael N. and Donath, Marc
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0021-972X
e-ISSN:1945-7197
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:26 Jun 2020 12:29
Deposited On:26 Jun 2020 12:29

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