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OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients

BACKGROUND: Adrenal incidentalomas (AI) are frequently associated with mild autonomous cortisol excess (MACE). The 1mg-dexamethasone suppression test (1mg-DST) differentiates MACE into MACE-1 (possible MACE; post-Dex cortisol 50-138 nmol/L) and MACE-2 (definitive MACE; post-Dex cortisol >138 nmol...

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Autores principales: Prete, Alessandro, Taylor, Angela, Alice, Sitch, Gilligan, Lorna, Vassiliadi, Dimitra, Ambroziak, Urszula, Lang, Katharina, Kastelan, Darko, Tabarin, Antoine, Dennedy, Michael, Ueland, Grethe, Quinkler, Marcus, Masjkur, Jimmy, Fassnacht, Martin, Ivovic, Miomira, Terzolo, Massimo, Beuschlein, Felix, Manolopoulos, Konstantinos, O'Reilly, Michael, Tsagarakis, Stylianos, Shackleton, Cedric, Deeks, Jonathan, Bancos, Irina, Arlt, Wiebke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554888/
http://dx.doi.org/10.1210/js.2019-OR29-2
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author Prete, Alessandro
Taylor, Angela
Alice, Sitch
Gilligan, Lorna
Vassiliadi, Dimitra
Ambroziak, Urszula
Lang, Katharina
Kastelan, Darko
Tabarin, Antoine
Dennedy, Michael
Ueland, Grethe
Quinkler, Marcus
Masjkur, Jimmy
Fassnacht, Martin
Ivovic, Miomira
Terzolo, Massimo
Beuschlein, Felix
Manolopoulos, Konstantinos
O'Reilly, Michael
Tsagarakis, Stylianos
Shackleton, Cedric
Deeks, Jonathan
Bancos, Irina
Arlt, Wiebke
author_facet Prete, Alessandro
Taylor, Angela
Alice, Sitch
Gilligan, Lorna
Vassiliadi, Dimitra
Ambroziak, Urszula
Lang, Katharina
Kastelan, Darko
Tabarin, Antoine
Dennedy, Michael
Ueland, Grethe
Quinkler, Marcus
Masjkur, Jimmy
Fassnacht, Martin
Ivovic, Miomira
Terzolo, Massimo
Beuschlein, Felix
Manolopoulos, Konstantinos
O'Reilly, Michael
Tsagarakis, Stylianos
Shackleton, Cedric
Deeks, Jonathan
Bancos, Irina
Arlt, Wiebke
author_sort Prete, Alessandro
collection PubMed
description BACKGROUND: Adrenal incidentalomas (AI) are frequently associated with mild autonomous cortisol excess (MACE). The 1mg-dexamethasone suppression test (1mg-DST) differentiates MACE into MACE-1 (possible MACE; post-Dex cortisol 50-138 nmol/L) and MACE-2 (definitive MACE; post-Dex cortisol >138 nmol/L). MACE patients do not show clinically overt signs of hypercortisolism but are thought to carry a higher metabolic risk than nonfunctioning (NF) AIs. However, large-scale data about the metabolic impact of MACE are lacking. METHODS: We included 1208 patients with benign AIs and 1mg-DST results prospectively recruited as part of the ENSAT EURINE-ACT study. Clinical information and 24-h urines were available for all patients. Results of mass spectrometry-based urinary steroid profiling were compared to 162 healthy controls and 56 patients with overt adrenal Cushing’s syndrome (CUSH), using a sex- and age-adjusted linear regression model. RESULTS: MACE was found in 48% of adrenal incidentaloma patients (MACE-1 37%, MACE-2 11%), predominantly affecting women (NF 64%, MACE-1 67%, MACE-2 77%). MACE patients were significantly older than those with NF (p<0.001). MACE AIs were larger (median 32mm vs. 22mm in NF) and more often bilateral (31% vs. 17% in NF). The presence and grade of MACE were significantly linked to metabolic risk as assessed by prevalence of hypertension (NF 64%, MACE-1 75%, MACE-2 78%), type 2 diabetes (NF 20%, MACE-1 27%, MACE-2 30%), use of lipid-lowering medications (NF 40%, MACE-1 54%, MACE-2 52%), and osteopenia/osteoporosis (NF 37%, MACE-1 50%, MACE-2 56%) (all p<0.01 by Fisher’s exact test). Patients with MACE and type 2 diabetes more frequently required insulin treatment (31% vs. 15% in NF; p<0.01), and those with hypertension more often needed ≥3 medications (42% vs. 35% in NF; p<0.01). Urinary steroid metabolome analysis of MACE urines revealed a profile characterized by decreased androgen metabolites and increased glucocorticoid metabolites, resembling the profile of CUSH patients, with the latter also showing significantly increased mineralocorticoid precursor excretion (corticosterone and 11- deoxycorticosterone metabolites) (all p<0.001 vs. controls). CONCLUSIONS: MACE is highly prevalent in AIs and associated with an increased burden of metabolic co-morbidities. In addition, the similarities between the MACE and CUSH steroid metabolomes suggests that MACE is both a highly relevant clinical and biochemical entity.
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spelling pubmed-65548882019-06-13 OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients Prete, Alessandro Taylor, Angela Alice, Sitch Gilligan, Lorna Vassiliadi, Dimitra Ambroziak, Urszula Lang, Katharina Kastelan, Darko Tabarin, Antoine Dennedy, Michael Ueland, Grethe Quinkler, Marcus Masjkur, Jimmy Fassnacht, Martin Ivovic, Miomira Terzolo, Massimo Beuschlein, Felix Manolopoulos, Konstantinos O'Reilly, Michael Tsagarakis, Stylianos Shackleton, Cedric Deeks, Jonathan Bancos, Irina Arlt, Wiebke J Endocr Soc Adrenal BACKGROUND: Adrenal incidentalomas (AI) are frequently associated with mild autonomous cortisol excess (MACE). The 1mg-dexamethasone suppression test (1mg-DST) differentiates MACE into MACE-1 (possible MACE; post-Dex cortisol 50-138 nmol/L) and MACE-2 (definitive MACE; post-Dex cortisol >138 nmol/L). MACE patients do not show clinically overt signs of hypercortisolism but are thought to carry a higher metabolic risk than nonfunctioning (NF) AIs. However, large-scale data about the metabolic impact of MACE are lacking. METHODS: We included 1208 patients with benign AIs and 1mg-DST results prospectively recruited as part of the ENSAT EURINE-ACT study. Clinical information and 24-h urines were available for all patients. Results of mass spectrometry-based urinary steroid profiling were compared to 162 healthy controls and 56 patients with overt adrenal Cushing’s syndrome (CUSH), using a sex- and age-adjusted linear regression model. RESULTS: MACE was found in 48% of adrenal incidentaloma patients (MACE-1 37%, MACE-2 11%), predominantly affecting women (NF 64%, MACE-1 67%, MACE-2 77%). MACE patients were significantly older than those with NF (p<0.001). MACE AIs were larger (median 32mm vs. 22mm in NF) and more often bilateral (31% vs. 17% in NF). The presence and grade of MACE were significantly linked to metabolic risk as assessed by prevalence of hypertension (NF 64%, MACE-1 75%, MACE-2 78%), type 2 diabetes (NF 20%, MACE-1 27%, MACE-2 30%), use of lipid-lowering medications (NF 40%, MACE-1 54%, MACE-2 52%), and osteopenia/osteoporosis (NF 37%, MACE-1 50%, MACE-2 56%) (all p<0.01 by Fisher’s exact test). Patients with MACE and type 2 diabetes more frequently required insulin treatment (31% vs. 15% in NF; p<0.01), and those with hypertension more often needed ≥3 medications (42% vs. 35% in NF; p<0.01). Urinary steroid metabolome analysis of MACE urines revealed a profile characterized by decreased androgen metabolites and increased glucocorticoid metabolites, resembling the profile of CUSH patients, with the latter also showing significantly increased mineralocorticoid precursor excretion (corticosterone and 11- deoxycorticosterone metabolites) (all p<0.001 vs. controls). CONCLUSIONS: MACE is highly prevalent in AIs and associated with an increased burden of metabolic co-morbidities. In addition, the similarities between the MACE and CUSH steroid metabolomes suggests that MACE is both a highly relevant clinical and biochemical entity. Endocrine Society 2019-04-30 /pmc/articles/PMC6554888/ http://dx.doi.org/10.1210/js.2019-OR29-2 Text en Copyright © 2019 Endocrine Society https://creativecommons.org/licenses/by-nc-nd/4.0/ This article has been published under the terms of the Creative Commons Attribution Non-Commercial, No-Derivatives License (CC BY-NC-ND; https://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Adrenal
Prete, Alessandro
Taylor, Angela
Alice, Sitch
Gilligan, Lorna
Vassiliadi, Dimitra
Ambroziak, Urszula
Lang, Katharina
Kastelan, Darko
Tabarin, Antoine
Dennedy, Michael
Ueland, Grethe
Quinkler, Marcus
Masjkur, Jimmy
Fassnacht, Martin
Ivovic, Miomira
Terzolo, Massimo
Beuschlein, Felix
Manolopoulos, Konstantinos
O'Reilly, Michael
Tsagarakis, Stylianos
Shackleton, Cedric
Deeks, Jonathan
Bancos, Irina
Arlt, Wiebke
OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title_full OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title_fullStr OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title_full_unstemmed OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title_short OR29-2 Mild Autonomous Cortisol Excess (MACE) in Adrenal Incidentalomas - Metabolic Risk Profile and Urinary Steroid Metabolome Analysis in 1208 Prospectively Recruited Patients
title_sort or29-2 mild autonomous cortisol excess (mace) in adrenal incidentalomas - metabolic risk profile and urinary steroid metabolome analysis in 1208 prospectively recruited patients
topic Adrenal
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554888/
http://dx.doi.org/10.1210/js.2019-OR29-2
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