In April 2016 Manchester eScholar was replaced by the University of Manchester’s new Research Information Management System, Pure. In the autumn the University’s research outputs will be available to search and browse via a new Research Portal. Until then the University’s full publication record can be accessed via a temporary portal and the old eScholar content is available to search and browse via this archive.

Corticosteroid-binding globulin regulates cortisol pharmacokinetics.

Perogamvros, I; Aarons, L; Miller, A G; Trainer, P J; Ray, D W

Clinical endocrinology. 2011;74(1):30-6.

Access to files

Full-text and supplementary files are not available from Manchester eScholar. Full-text is available externally using the following links:

Full-text held externally

Abstract

OBJECTIVE: Corticosteroid-binding globulin (CBG) is the principal carrier for cortisol in the circulation. Variations in CBG-binding capacity are predicted to alter total serum cortisol disposition, but free serum cortisol is believed to be unaffected. Unbound cortisol pharmacokinetics (PK) have not been studied in the context of CBG changes. We aimed to assess the regulation of cortisol PK by CBG. DESIGN AND SUBJECTS: Women on oestrogens [oral contraceptive pill, (OCP)], patients homozygous for a nonfunctioning CBG variant (CBG null) and healthy controls (HV) were studied before and after IV and oral administration of hydrocortisone 20 mg. MEASUREMENTS: PK parameters were studied for total serum cortisol (SerF), free serum cortisol (FreeF) and cortisone (FreeE), and salivary cortisol (SalF) and cortisone (SalE): area under the curve (AUC), clearance (CL), half-life and volume of distribution (V(d)). RESULTS: Following IV hydrocortisone, AUC and half-life of SerF were significantly higher in the OCP group and lower in the CBG null. SerF CL and V(d) were significantly lower in the OCP group and increased in the CBG null, compared to HV. PK parameters for FreeF and the salivary biomarkers were not different between the CBG null and HV, although OCP patients still had higher AUC compared to HV and prolonged half-life. These findings were confirmed following oral hydrocortisone, but concentration-time profiles were highly heterogeneous and SalF interpretation was problematic because of oral contamination. CONCLUSIONS: We have demonstrated that CBG has a distinct effect on cortisol PK. When CBG binding is disrupted, FreeF retains normal PK characteristics, although CBG null patients lack a CBG-bound pool of readily releasable cortisol. Women on oestrogens may have altered free serum cortisol kinetics and thus may be potentially overexposed to glucocorticoids.

Bibliographic metadata

Type of resource:
Content type:
Publication type:
Published date:
Journal title:
Abbreviated journal title:
ISSN:
Place of publication:
England
Volume:
74
Issue:
1
Pagination:
30-6
Digital Object Identifier:
10.1111/j.1365-2265.2010.03897.x
Pubmed Identifier:
21054475
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:133079
Created by:
Ray, David
Created:
13th October, 2011, 14:16:05
Last modified by:
Ray, David
Last modified:
19th August, 2013, 18:18:56

Can we help?

The library chat service will be available from 11am-3pm Monday to Friday (excluding Bank Holidays). You can also email your enquiry to us.