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DC Field | Value | Language |
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dc.contributor.author | Vega Beyhart, Arturo | - |
dc.contributor.author | Laguna Moreno, Javier | - |
dc.contributor.author | Díaz Catalán, Daniela | - |
dc.contributor.author | Boswell, Laura | - |
dc.contributor.author | Mora Porta, Mireia | - |
dc.contributor.author | Halperin, Irene | - |
dc.contributor.author | Casals, Gregori | - |
dc.contributor.author | Hanzu, Felicia Alexandra | - |
dc.date.accessioned | 2024-04-17T15:20:23Z | - |
dc.date.available | 2024-04-17T15:20:23Z | - |
dc.date.issued | 2022-02-23 | - |
dc.identifier.issn | 1664-2392 | - |
dc.identifier.uri | http://hdl.handle.net/2445/210080 | - |
dc.description.abstract | Introduction: Twenty-four-hour urinary free cortisol (24h-UFC) is the most used test for follow-up decision-making in patients with Cushing syndrome (CS) under medical treatment. However, 24h-UFC determinations by immunoassays (IA) are commonly overestimated because of steroid metabolites' cross-reaction. It is still uncertain how ketoconazole (KTZ)- and metyrapone (MTP)-induced changes on the urinary steroid metabolites can alter the 24h-UFC*IA determinations' reliability. Methods: 24h-UFC was analyzed by IA and gas chromatography-mass spectrometry (GC-MS) in 193 samples (81 before treatment, 73 during KTZ, and 39 during MTP) from 34 CS patients. In addition, urinary steroidome was analyzed by GC-MS on each patient before and during treatment. Results: Before treatment, 24h-UFC*IA determinations were overestimated by a factor of 1.75 (95% CI 1.60-1.94) compared to those by GC-MS. However, during KTZ treatment, 24h-UFC*IA results were similar (0.98:1) to those by GC-MS (95% CI, 0.83-1.20). In patients taking MTP, IA bias only decreased 0.55, resulting in persistence of an overestimation factor of 1.33:1 (95% CI, 1.09-1.76). High method agreement between GC-MS and IA before treatment (R2 = 0.954) declined in patients under KTZ (R2 = 0.632) but not in MTP (R2 = 0.917). Upper limit normal (ULN) reductions in patients taking KTZ were 27% larger when using 24h-UFC*IA compared to 24h-UFC*GC-MS, which resulted in higher false efficacy and misleading biochemical classification of 15% of patients. Urinary excretion changes of 22 urinary steroid metabolites explained 86% of the 24h-UFC*IA interference. Larger urinary excretion reductions of 6β-hydroxy-cortisol, 20α-dihydrocortisol, and 18-hydroxy-cortisol in patients with KTZ elucidated the higher 24h-UFC*IA bias decrement compared to MTP-treated patients. Conclusion: KTZ and MTP alter the urinary excretion of IA cross-reactive steroid metabolites, thus decreasing the cross-reactive interference of 24h-UFC*IA determinations present before treatment. Consequently, this interference reduction in 24h-UFC*IA leads to loss of method agreement with GC-MS and high risk of overestimating the biochemical impact of KTZ and MTP in controlling CS because of poor reliability of reference ranges and ULN. | - |
dc.format.extent | 12 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fendo.2022.833644 | - |
dc.relation.ispartof | Frontiers In Endocrinology, 2022, vol. 13, p. 833644 | - |
dc.relation.uri | https://doi.org/10.3389/fendo.2022.833644 | - |
dc.rights | cc-by (c) Vega-Beyhart, A. et al., 2022 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | - |
dc.source | Articles publicats en revistes (Medicina) | - |
dc.subject.classification | Síndrome de Cushing | - |
dc.subject.classification | Immunoassaig | - |
dc.subject.classification | Ketoconazole | - |
dc.subject.classification | Esteroides | - |
dc.subject.other | Cushing's syndrome | - |
dc.subject.other | Immunoassay | - |
dc.subject.other | Ketoconazole | - |
dc.subject.other | Steroids | - |
dc.title | Ketoconazole- and Metyrapone-Induced Reductions on Urinary Steroid Metabolites Alter the Urinary Free Cortisol Immunoassay Reliability in Cushing Syndrome | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 743043 | - |
dc.date.updated | 2024-04-17T15:20:28Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.idimarina | 9300542 | - |
dc.identifier.pmid | 35282465 | - |
Appears in Collections: | Articles publicats en revistes (Medicina) Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) |
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