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Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study

BACKGROUND: Incidental adrenal masses are commonly detected during imaging for other pathologies. 10% of the elderly population has an ‘adrenal incidentaloma’, up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistan...

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Autores principales: Debono, Miguel, Chadarevian, Rita, Eastell, Richard, Ross, Richard J., Newell-Price, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618218/
https://www.ncbi.nlm.nih.gov/pubmed/23577182
http://dx.doi.org/10.1371/journal.pone.0060984
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author Debono, Miguel
Chadarevian, Rita
Eastell, Richard
Ross, Richard J.
Newell-Price, John
author_facet Debono, Miguel
Chadarevian, Rita
Eastell, Richard
Ross, Richard J.
Newell-Price, John
author_sort Debono, Miguel
collection PubMed
description BACKGROUND: Incidental adrenal masses are commonly detected during imaging for other pathologies. 10% of the elderly population has an ‘adrenal incidentaloma’, up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistance. Cortisol excess is known to cause insulin resistance, an independent cardiovascular risk marker, however in patients with adrenal incidentalomas it is unknown whether their insulin resistance is secondary to the excess cortisol and therefore potentially reversible. In a proof of concept study we examined the short-term effects of glucocorticoid receptor (GR) antagonism in patients with an adrenal incidentaloma to determine whether their insulin resistance was reversible. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective open-label pilot study, six individuals with adrenal incidentalomas and autonomous cortisol secretion were treated with mifepristone (a GR antagonist) 200 mg twice daily and studied for 4 weeks on a Clinical Research Facility. Insulin resistance at four weeks was assessed by insulin resistance indices, lnHOMA-IR and lnMatsuda, and AUC insulin during a 2-hour glucose tolerance test. Biochemical evidence of GR blockade was shown in all individuals and across the group there was a significant reduction in insulin resistance: lnHOMA-IR (1.0vs0.6; p = 0.03), lnHOMA-%beta (4.8vs4.3; p = 0.03) and lnMatsuda (1.2vs1.6; p = 0.03). Five out of six individuals showed a reduction in insulin AUC >7237 pmol/l.min, and in two patients this showed a clinically significant cardiovascular benefit (as defined by the Helsinki heart study). CONCLUSIONS: Short-term GR antagonism is sufficient to reduce insulin resistance in some individuals with adrenal incidentalomas and mild cortisol excess. Further assessment is required to assess if the responses may be used to stratify therapy as adrenal incidentalomas may be a common remediable cause of increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00721201
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spelling pubmed-36182182013-04-10 Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study Debono, Miguel Chadarevian, Rita Eastell, Richard Ross, Richard J. Newell-Price, John PLoS One Research Article BACKGROUND: Incidental adrenal masses are commonly detected during imaging for other pathologies. 10% of the elderly population has an ‘adrenal incidentaloma’, up to 20% of these show low-grade autonomous cortisol secretion and 60% of patients with autonomous cortisol secretion have insulin resistance. Cortisol excess is known to cause insulin resistance, an independent cardiovascular risk marker, however in patients with adrenal incidentalomas it is unknown whether their insulin resistance is secondary to the excess cortisol and therefore potentially reversible. In a proof of concept study we examined the short-term effects of glucocorticoid receptor (GR) antagonism in patients with an adrenal incidentaloma to determine whether their insulin resistance was reversible. METHODOLOGY/PRINCIPAL FINDINGS: In a prospective open-label pilot study, six individuals with adrenal incidentalomas and autonomous cortisol secretion were treated with mifepristone (a GR antagonist) 200 mg twice daily and studied for 4 weeks on a Clinical Research Facility. Insulin resistance at four weeks was assessed by insulin resistance indices, lnHOMA-IR and lnMatsuda, and AUC insulin during a 2-hour glucose tolerance test. Biochemical evidence of GR blockade was shown in all individuals and across the group there was a significant reduction in insulin resistance: lnHOMA-IR (1.0vs0.6; p = 0.03), lnHOMA-%beta (4.8vs4.3; p = 0.03) and lnMatsuda (1.2vs1.6; p = 0.03). Five out of six individuals showed a reduction in insulin AUC >7237 pmol/l.min, and in two patients this showed a clinically significant cardiovascular benefit (as defined by the Helsinki heart study). CONCLUSIONS: Short-term GR antagonism is sufficient to reduce insulin resistance in some individuals with adrenal incidentalomas and mild cortisol excess. Further assessment is required to assess if the responses may be used to stratify therapy as adrenal incidentalomas may be a common remediable cause of increased cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT00721201 Public Library of Science 2013-04-05 /pmc/articles/PMC3618218/ /pubmed/23577182 http://dx.doi.org/10.1371/journal.pone.0060984 Text en © 2013 Debono et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Debono, Miguel
Chadarevian, Rita
Eastell, Richard
Ross, Richard J.
Newell-Price, John
Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title_full Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title_fullStr Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title_full_unstemmed Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title_short Mifepristone Reduces Insulin Resistance in Patient Volunteers with Adrenal Incidentalomas That Secrete Low Levels of Cortisol: A Pilot Study
title_sort mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol: a pilot study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3618218/
https://www.ncbi.nlm.nih.gov/pubmed/23577182
http://dx.doi.org/10.1371/journal.pone.0060984
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