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Pulsed glucocorticoid therapy successfully replaced physiological cortisol
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CHICAGO — Through a pulsed subcutaneous regimen, physiological circadian and ultradian cortisol were successfully replaced, according to research presented at the joint meeting of the International Congress of Endocrinology and the Endocrine Society.
“We are in a position to reproduce a more physiological looking cortisol, circadian and ultradian rhythms,” Georgina M Russell, MBBC, MRCP, PhD, of the University of Bristol, United Kingdom, said during her presentation.
Russell and fellow researchers tested the novel pulsed hydrocortisone therapy, delivered via a portable infusion pump, in 22 healthy volunteers.
Participants underwent dexamethasone suppression (2 mg daily), then received hydrocortisone subcutaneously as two individual pulses of secretion; doses were high, medium or low in size.
Over the course of 7 hours, a human automated blood sampling system collected samples in intervals of 10 minutes for cortisol and 1 hour for adrenocorticotropic hormone (to confirm endogenous adrenal suppression). Size and frequency of doses were adjusted to meet physiological blood levels of cortisol.
For a further pilot study, participants received dexamethasone (4 mg daily) to inhibit endogenous hypothalamo-pituitary-adrenocortical activity, with subcutaneous hydrocortisone infused via pump in eight pulses — three high, three medium and two low. Blood samples were taken at corresponding times, but over 24 hours. This produced a circadian cortisol peak of ≥500 nmol/L with a trough of ≤100 nmol/L; a definitive “on/off” period was observed between individual pulses.
“Perhaps now we can use this tool to be able to assess what a more optimal dose would be for our patients,” Russell said, “and use it as a tool to assess cognitive, metabolic and cardiovascular and immunological importance of normal physiological patterns of cortisol in patients on steroid replacement.” — by Allegra Tiver
For More Information: Russell GM. Abstract OR48-1. Presented at: The joint meeting of the International Congress of Endocrinology and the Endocrine Society; June 21-24, 2014; Chicago.
Disclosures: Russell reports no relevant disclosures.
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Jeremy W. Tomlinson, BA, BM, BCH, FRCP, PhD
We all produce hydrocortisone in a circadian rhythm and, within that, little spikes of cortisol. When we give traditional therapy, two or three doses per day as tablet, that doesn’t really mimic what we would normally be producing.
The questions are: If we can mimic in a better way what we would naturally be producing, does that have beneficial effects for patients? Does it improve their quality of life? Does it improve their side effects from glucocorticoids? Could we minimize the dose patients actually need, so we have less insulin resistance and less diabetes?
It may well be helpful, in that regard, to tailor individual doses. But the critical thing will be actually seeing the best clinical outcomes — improving quality of life, improving compliance and improving metabolic profile.
The technology is great. But we have to wonder how acceptable it will be for patients, since they have to wear a pump. It may be an acceptable therapy in a small number of patients where other therapies haven’t worked for whatever reason.
This is very, very early in development. It has potential but still way off from being adopted in mainstream.
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