Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia
IntroductionAdrenal vein sampling (AVS) is not a routine procedure in patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but has been used to determine lateralization of cortisol secretion in order to guide decision of unilateral adrenalectomy. Our aim was to characteri...
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1079508/full |
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| author | Ru Zhang German Rubinstein Sharmilee Vetrivel Sonja Kunz Frederick Vogel Lucas Bouys Jérôme Bertherat Matthias Kroiss Matthias Kroiss Sinan Deniz Andrea Osswald Thomas Knösel Martin Bidlingmaier Silviu Sbiera Martin Reincke Anna Riester |
| author_facet | Ru Zhang German Rubinstein Sharmilee Vetrivel Sonja Kunz Frederick Vogel Lucas Bouys Jérôme Bertherat Matthias Kroiss Matthias Kroiss Sinan Deniz Andrea Osswald Thomas Knösel Martin Bidlingmaier Silviu Sbiera Martin Reincke Anna Riester |
| author_sort | Ru Zhang |
| collection | DOAJ |
| description | IntroductionAdrenal vein sampling (AVS) is not a routine procedure in patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but has been used to determine lateralization of cortisol secretion in order to guide decision of unilateral adrenalectomy. Our aim was to characterize the steroid fingerprints in AVS samples of patients with PBMAH and hypercortisolism and to identify a reference hormone for AVS interpretation.MethodRetrospectively, we included 17 patients with PBMAH from the German Cushing’s registry who underwent AVS. 15 steroids were quantified in AVS and peripheral blood samples using LC-MS/MS. We calculated lateralization indices and conversion ratios indicative of steroidogenic enzyme activity to elucidate differences between individual adrenal steroidomes and in steroidogenic pathways.ResultsAdrenal volume was negatively correlated with peripheral cortisone (r=0.62, p<0.05). 24-hour urinary free cortisol correlated positively with peripheral androgens (rDHEA=0.57, rDHEAS=0.82, rA=0.73, rT=0.54, p<0.05). DHEA was found to be a powerful reference hormone with high selectivity index, which did not correlate with serume cortisol and has a short half-life. All investigated steroids showed lateralization in single patients indicating the heterogenous steroid secretion pattern in patients with PBMAH. The ratios of corticosterone/aldosterone (catalyzed by CYP11B2), androstenedione/dehydroepiandrosterone (catalyzed by HSD3B2) and cortisone/cortisol (catalyzed by HSD11B2) in adrenal vein samples were higher in smaller adrenals (p<0.05). ARMC5 mutation carriers (n=6) showed lower androstenedione/17-hydroxyprogesterone and higher testosterone/androstenedione (p<0.05) ratios in peripheral blood, in line with lower peripheral androstenedione concentrations (p<0.05).ConclusionSteroid profiling by LC-MS/MS led us to select DHEA as a candidate reference hormone for cortisol secretion. Lateralization and different steroid ratios showed that each steroid and all three steroidogenic pathways may be affected in PBMAH patients. In patients with germline ARMC5 mutations, the androgen pathway was particularly dysregulated. |
| first_indexed | 2024-04-13T11:10:14Z |
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| id | doaj.art-994ccb581cd94259baf62f6dad60fe30 |
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| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T11:10:14Z |
| publishDate | 2022-12-01 |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-994ccb581cd94259baf62f6dad60fe302022-12-22T02:49:10ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-12-011310.3389/fendo.2022.10795081079508Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasiaRu Zhang0German Rubinstein1Sharmilee Vetrivel2Sonja Kunz3Frederick Vogel4Lucas Bouys5Jérôme Bertherat6Matthias Kroiss7Matthias Kroiss8Sinan Deniz9Andrea Osswald10Thomas Knösel11Martin Bidlingmaier12Silviu Sbiera13Martin Reincke14Anna Riester15Medizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyInstitut Cochin, Université Paris-Cité, Paris, FranceInstitut Cochin, Université Paris-Cité, Paris, FranceMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, GermanyKlinik und Poliklinik für Radiologie, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyPathologisches Institut, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyDepartment of Internal Medicine I, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyMedizinische Klinik und Poliklinik IV, LMU Klinikum, Ludwig-Maximilians-University, Munich, GermanyIntroductionAdrenal vein sampling (AVS) is not a routine procedure in patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH), but has been used to determine lateralization of cortisol secretion in order to guide decision of unilateral adrenalectomy. Our aim was to characterize the steroid fingerprints in AVS samples of patients with PBMAH and hypercortisolism and to identify a reference hormone for AVS interpretation.MethodRetrospectively, we included 17 patients with PBMAH from the German Cushing’s registry who underwent AVS. 15 steroids were quantified in AVS and peripheral blood samples using LC-MS/MS. We calculated lateralization indices and conversion ratios indicative of steroidogenic enzyme activity to elucidate differences between individual adrenal steroidomes and in steroidogenic pathways.ResultsAdrenal volume was negatively correlated with peripheral cortisone (r=0.62, p<0.05). 24-hour urinary free cortisol correlated positively with peripheral androgens (rDHEA=0.57, rDHEAS=0.82, rA=0.73, rT=0.54, p<0.05). DHEA was found to be a powerful reference hormone with high selectivity index, which did not correlate with serume cortisol and has a short half-life. All investigated steroids showed lateralization in single patients indicating the heterogenous steroid secretion pattern in patients with PBMAH. The ratios of corticosterone/aldosterone (catalyzed by CYP11B2), androstenedione/dehydroepiandrosterone (catalyzed by HSD3B2) and cortisone/cortisol (catalyzed by HSD11B2) in adrenal vein samples were higher in smaller adrenals (p<0.05). ARMC5 mutation carriers (n=6) showed lower androstenedione/17-hydroxyprogesterone and higher testosterone/androstenedione (p<0.05) ratios in peripheral blood, in line with lower peripheral androstenedione concentrations (p<0.05).ConclusionSteroid profiling by LC-MS/MS led us to select DHEA as a candidate reference hormone for cortisol secretion. Lateralization and different steroid ratios showed that each steroid and all three steroidogenic pathways may be affected in PBMAH patients. In patients with germline ARMC5 mutations, the androgen pathway was particularly dysregulated.https://www.frontiersin.org/articles/10.3389/fendo.2022.1079508/fullcortisolAVSsteroidomeLC-MS/MSadenomaDHEA |
| spellingShingle | Ru Zhang German Rubinstein Sharmilee Vetrivel Sonja Kunz Frederick Vogel Lucas Bouys Jérôme Bertherat Matthias Kroiss Matthias Kroiss Sinan Deniz Andrea Osswald Thomas Knösel Martin Bidlingmaier Silviu Sbiera Martin Reincke Anna Riester Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia Frontiers in Endocrinology cortisol AVS steroidome LC-MS/MS adenoma DHEA |
| title | Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| title_full | Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| title_fullStr | Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| title_full_unstemmed | Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| title_short | Steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| title_sort | steroid profiling using liquid chromatography mass spectrometry during adrenal vein sampling in patients with primary bilateral macronodular adrenocortical hyperplasia |
| topic | cortisol AVS steroidome LC-MS/MS adenoma DHEA |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1079508/full |
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