Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome
Background: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing’s syndrome. Changes in the renin–angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pat...
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Bioscientifica
2025-01-01
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| Series: | Endocrine Connections |
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| Online Access: | https://ec.bioscientifica.com/view/journals/ec/14/2/EC-24-0617.xml |
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| author | Peter Wolf Simon Travers Oliver Domenig Stephanie Baron Anne Blanchard Khaoula Bouazizi Nadjia Kachenoura Sylvie Salenave Marko Poglitsch Alban Redheuil Severine Trabado Jacques Young Philippe Chanson Peter Kamenický |
| author_facet | Peter Wolf Simon Travers Oliver Domenig Stephanie Baron Anne Blanchard Khaoula Bouazizi Nadjia Kachenoura Sylvie Salenave Marko Poglitsch Alban Redheuil Severine Trabado Jacques Young Philippe Chanson Peter Kamenický |
| author_sort | Peter Wolf |
| collection | DOAJ |
| description | Background: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing’s syndrome. Changes in the renin–angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess. Methods: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing’s syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index. Angiotensin metabolites and adrenal steroids were measured by liquid chromatography tandem mass spectrometry, and their relation to blood pressure and cardiac structure was evaluated. Results: Concentrations of angiotensin I and angiotensin II were comparable, but the angiotensin-converting enzyme activity was significantly lower (2.19 (1.67; 3.08) vs 4.07 (3.1; 5.6); P < 0.001) in patients compared to controls. Aldosterone concentrations were significantly lower (6.9 (6.9; 124.1) vs 239.9 (181.4; 321.9) pmol/L; P < 0.001) in the group of patients, but adrenal aldosterone precursor metabolites were comparable between patients and controls. Inverse correlations were observed for 24 h urinary free cortisol and aldosterone with the ratio of left ventricular mass to end-diastolic volume (r = 0.470, P = 0.012 and r = −0.367, P = 0.046, respectively). Conclusions: We describe a disease-specific profile of angiotensin metabolites in patients with ACTH-dependent Cushing’s syndrome. Low levels of aldosterone in the presence of unchanged precursor metabolites indicate a direct inhibitory action of cortisol excess on the aldosterone synthase. Furthermore, glucocorticoid excess per se drives cardiac muscle remodeling. |
| format | Article |
| id | doaj-art-256175dfc34b4e2a9bc6b2f7b0f5750d |
| institution | Kabale University |
| issn | 2049-3614 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj-art-256175dfc34b4e2a9bc6b2f7b0f5750d2025-02-05T10:14:00ZengBioscientificaEndocrine Connections2049-36142025-01-0114210.1530/EC-24-06171Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndromePeter Wolf0Simon Travers1Oliver Domenig2Stephanie Baron3Anne Blanchard4Khaoula Bouazizi5Nadjia Kachenoura6Sylvie Salenave7Marko Poglitsch8Alban Redheuil9Severine Trabado10Jacques Young11Philippe Chanson12Peter Kamenický13Université Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, FranceUniversité Paris Cité, PARCC, Inserm, Paris, FranceAttoquant Diagnostics, Vienna, AustriaUniversité Paris Cité, PARCC, Inserm, Paris, FranceUniversité Paris Cité, PARCC, Inserm, Paris, FranceSorbonne Université, CNRS, Inserm, Laboratoire d’Imagerie Biomédicale, LIB, Paris, FranceSorbonne Université, CNRS, Inserm, Laboratoire d’Imagerie Biomédicale, LIB, Paris, FranceUniversité Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, FranceAttoquant Diagnostics, Vienna, AustriaInstitut de Cardiométabolisme et Nutrition (ICAN), Paris, FranceAssistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service de Génétique Moléculaire, Pharmacogénétique et Hormonologie, Le Kremlin-Bicêtre, FranceUniversité Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, FranceUniversité Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, FranceUniversité Paris-Saclay, Inserm, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Service d’Endocrinologie et des Maladies de la Reproduction, Centre de Référence des Maladies Rares de l’Hypophyse, Le Kremlin-Bicêtre, FranceBackground: Arterial hypertension and left ventricular hypertrophy and remodeling are independent cardiovascular risk factors in patients with Cushing’s syndrome. Changes in the renin–angiotensin system and in the mineralocorticoid axis activity could be involved as potential mechanisms in their pathogenesis, in addition to cortisol excess. Methods: In this ancillary study of our previous study prospectively investigating patients with ACTH-dependent Cushing’s syndrome by cardiac magnetic resonance imaging (NCT02202902), 11 patients without any interfering medication were cross-sectionally compared to 20 control subjects matched for age, sex and body mass index. Angiotensin metabolites and adrenal steroids were measured by liquid chromatography tandem mass spectrometry, and their relation to blood pressure and cardiac structure was evaluated. Results: Concentrations of angiotensin I and angiotensin II were comparable, but the angiotensin-converting enzyme activity was significantly lower (2.19 (1.67; 3.08) vs 4.07 (3.1; 5.6); P < 0.001) in patients compared to controls. Aldosterone concentrations were significantly lower (6.9 (6.9; 124.1) vs 239.9 (181.4; 321.9) pmol/L; P < 0.001) in the group of patients, but adrenal aldosterone precursor metabolites were comparable between patients and controls. Inverse correlations were observed for 24 h urinary free cortisol and aldosterone with the ratio of left ventricular mass to end-diastolic volume (r = 0.470, P = 0.012 and r = −0.367, P = 0.046, respectively). Conclusions: We describe a disease-specific profile of angiotensin metabolites in patients with ACTH-dependent Cushing’s syndrome. Low levels of aldosterone in the presence of unchanged precursor metabolites indicate a direct inhibitory action of cortisol excess on the aldosterone synthase. Furthermore, glucocorticoid excess per se drives cardiac muscle remodeling.https://ec.bioscientifica.com/view/journals/ec/14/2/EC-24-0617.xmlcushing’s syndromehypertensionangiotensinaldosteroneras system |
| spellingShingle | Peter Wolf Simon Travers Oliver Domenig Stephanie Baron Anne Blanchard Khaoula Bouazizi Nadjia Kachenoura Sylvie Salenave Marko Poglitsch Alban Redheuil Severine Trabado Jacques Young Philippe Chanson Peter Kamenický Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome Endocrine Connections cushing’s syndrome hypertension angiotensin aldosterone ras system |
| title | Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome |
| title_full | Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome |
| title_fullStr | Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome |
| title_full_unstemmed | Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome |
| title_short | Mineralocorticoid axis activity and cardiac remodeling in patients with ACTH-dependent Cushing’s syndrome |
| title_sort | mineralocorticoid axis activity and cardiac remodeling in patients with acth dependent cushing s syndrome |
| topic | cushing’s syndrome hypertension angiotensin aldosterone ras system |
| url | https://ec.bioscientifica.com/view/journals/ec/14/2/EC-24-0617.xml |
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