Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review
In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/22/13821 |
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| author | Xurong Mai Mitsuhiro Kometani Takashi Yoneda |
| author_facet | Xurong Mai Mitsuhiro Kometani Takashi Yoneda |
| author_sort | Xurong Mai |
| collection | DOAJ |
| description | In this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs. |
| first_indexed | 2024-03-09T18:17:18Z |
| format | Article |
| id | doaj.art-08eadd06131d4098b806710d8250fa0f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T18:17:18Z |
| publishDate | 2022-11-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-08eadd06131d4098b806710d8250fa0f2023-11-24T08:33:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-11-0123221382110.3390/ijms232213821Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A ReviewXurong Mai0Mitsuhiro Kometani1Takashi Yoneda2Department of Health Promotion and Medicine of the Future, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Ishikawa, JapanDepartment of Health Promotion and Medicine of the Future, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Ishikawa, JapanDepartment of Health Promotion and Medicine of the Future, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-8641, Ishikawa, JapanIn this review, we describe previous basic and clinical studies on autonomous aldosterone production. Over the past decades, mineralocorticoid receptor antagonists (MRAs) have been found to concentration-dependently inhibit steroidogenesis in different degrees. However, many studies have proven the suppressive effects of MRAs on the activities of hormone synthase. The probable factors of cytochrome P-450 reduction, both in microsomes and mitochondria, have also been considered: (1) one of the spironolactone metabolite forms had destructive function, except canrenone, (2) 7α-thio-spironolactone was an obligatory intermediate in the spironolactone-induced CYP450 decrease, and (3) the contributing steroids should have 7α-methylthio or 7α-methylsulfone groups. In previous clinical research, spironolactone-body-containing cells showed a type II pattern of enzyme activity (i.e., enhanced 3β-hydroxysteroid dehydrogenase, glucose-6-phosphate, and NADP-isocitrate dehydrogenase activities and weaken succinate dehydrogenase activity), and the subcapsular micronodules composed of spironolactone-body-containing cells also exhibited a type II pattern and excess aldosterone secretion, indicating that the subcapsular micronodules might be the root of aldosterone-producing adenoma. Moreover, combined with the potential impeditive function to aldosterone secretion, a few cases of spontaneous remission of primary aldosteronism, with normal ranges of blood pressure, plasma potassium, plasma renin activity, and aldosterone renin ratio, have been reported after long-term treatment with MRAs.https://www.mdpi.com/1422-0067/23/22/13821primary aldosteronismremissionmineralocorticoid receptor antagoniststeroidogenesis enzyme |
| spellingShingle | Xurong Mai Mitsuhiro Kometani Takashi Yoneda Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review International Journal of Molecular Sciences primary aldosteronism remission mineralocorticoid receptor antagonist steroidogenesis enzyme |
| title | Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review |
| title_full | Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review |
| title_fullStr | Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review |
| title_full_unstemmed | Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review |
| title_short | Spontaneous Remission of Primary Aldosteronism with Mineralocorticoid Receptor Antagonist Therapy: A Review |
| title_sort | spontaneous remission of primary aldosteronism with mineralocorticoid receptor antagonist therapy a review |
| topic | primary aldosteronism remission mineralocorticoid receptor antagonist steroidogenesis enzyme |
| url | https://www.mdpi.com/1422-0067/23/22/13821 |
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