Acute effect of increasing glucocorticoid replacement dose on cardiovascular risk and insulin sensitivity in patients with adrenocorticotrophin deficiency

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dc.contributor.authorPetersons, C.
dc.contributor.authorMangelsdorf, B.
dc.contributor.authorThompson, C.
dc.contributor.authorBurt, M.
dc.date.issued2014
dc.description.abstractContext: Higher hydrocortisone doses are associated with increased overall and cardiovascular mortality in ACTH-deficient patients. The mechanisms underlying this association have not been fully defined. Objective: The aim of the study was to determine whether increasing hydrocortisone (or equivalent) to 30 mg/d in ACTH-deficient patients increased cardiovascular risk and whether a reduction in insulin sensitivity and attenuation of insulin’s hemodynamic effects was responsible for this effect. Design: We conducted an open interventional study between 2011 and 2013. Setting: The study was performed in the Endocrine Research Unit, Repatriation General Hospital, Adelaide, Australia. Patients: Seventeen ACTH-deficient subjects taking hydrocortisone (≤ 20 mg/d) for at least 6 months were studied. Intervention: Subjects were studied before and after a 7-day increase in hydrocortisone to 30 mg/d. Main Outcome Measure: The primary outcome was the change in pulse wave velocity, both fasting and after a 75-g oral glucose load. Results: Fasting and post-glucose load pulse wave velocities were not significantly different on the higher glucocorticoid dose. Fasting augmentation index (24.9 ± 2.7 vs 22.6 ± 2.6%; P=.04) and reactive hyperemia index (2.3 ± 0.2 vs 2.0 ± 0.2; P=0.04) were lower on the higher glucocorticoid dose, with no significant difference in the post-glucose load changes in these variables. There were no significant changes in insulin sensitivity or secretion on the higher glucocorticoid dose. Conclusions: Endothelial dysfunction may contribute to the increased cardiovascular mortality associated with higher glucocorticoid doses. This may be a direct glucocorticoid effect, not mediated by insulin resistance. ACTH-deficient patients should thus be prescribed the lowest safe glucocorticoid replacement dose.
dc.description.statementofresponsibilityCarolyn J. Petersons, Brenda L. Mangelsdorf, Campbell H. Thompson, and Morton G. Burt
dc.identifier.citationJournal of Clinical Endocrinology and Metabolism (JCEM), 2014; 99(6):2269-2276
dc.identifier.doi10.1210/jc.2013-4305
dc.identifier.issn0021-972X
dc.identifier.issn1945-7197
dc.identifier.orcidThompson, C. [0000-0002-5164-3327]
dc.identifier.urihttp://hdl.handle.net/2440/102158
dc.language.isoen
dc.publisherEndocrine Society
dc.rightsCopyright © 2014 by the Endocrine Society
dc.source.urihttps://doi.org/10.1210/jc.2013-4305
dc.subjectHypopituitarism; glucocorticoid replacement
dc.titleAcute effect of increasing glucocorticoid replacement dose on cardiovascular risk and insulin sensitivity in patients with adrenocorticotrophin deficiency
dc.typeJournal article
pubs.publication-statusPublished

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