AbstractOptimal concentration of glucocorticoids, principally cortisol is key to regulating vital physiological functions. Two proteins bind majority i.e. 94 % or more of cortisol in general circulation-corticosteroid-binding globulin and albumin. The biological rhythm of total cortisol (bound and unbound) in man is well established whereas much less is known about that of biologically active free cortisol. Microdialysis is a well-established technique that enables the measurement of the active free component of cortisol. Repeated blood sampling, although routine is best carried out at a clinical facility for safety. As a result, little is known about dynamic functioning of hormonal systems with ultradian (shorter than 24hour) rhythms requiring prolonged frequent sampling in the most prevalent, and perhaps more relevant, physiological setting of an individual’s own environment.
In this thesis, I have described the validation of the technique of microdialysis for measuring free cortisol in healthy individuals followed by ambulatory sample collection using a portable automated microdialysate collector that was developed as a part of this project.
The profiles of free cortisol in two body compartments (subcutaneous tissue and intravenous) in response to Synacthen stimulation and dexamethasone suppression show good correlation with total cortisol, with no significant delay between the compartments. 24 hour measurements in healthy individuals confirmed the characteristic circadian variation in subcutaneous tissue similar to that of serum total cortisol. Furthermore, within an individual there was remarkable consistency of the circadian rhythm of subcutaneous free cortisol over 3 successive days even with dissimilar routines and activities during the three days. This is the first study whereby measurement of free cortisol continuously, including during sleep, up to 3 consecutive days in healthy people outside of a research facility setting, free to carry out their routine activities without major limitations has been reported.
|Date of Award||10 May 2016|
|Supervisor||Stafford L Lightman (Supervisor) & Astrid C E Linthorst (Supervisor)|