title: Subcutaneous pulsatile glucocorticoid replacement therapy.
abstract: The glucocorticoid hormone cortisol is released in pulses resulting in a complex and dynamic ultradian rhythm of plasma cortisol that underlies the classical circadian rhythm. These oscillating levels are also seen at the level of tissues such as the brain and trigger pulses of gene activation and downstream signalling. Different patterns of glucocorticoid presentation (constant vs pulsatile) result not only in different patterns of gene regulation but also in different neuroendocrine and behavioural responses. Current 'optimal' glucocorticoid replacement therapy results in smooth hormone blood levels and does not replicate physiological pulsatile cortisol secretion. Validation of a novel portable pulsatile continuous subcutaneous delivery system in healthy volunteers under dexamethasone and metyrapone suppression. Pulsatile subcutaneous hydrocortisone more closely replicates physiological circadian and ultradian rhythmicity.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, Dorothy Hodgkin Building, University of Bristol, Bristol, UK.
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Russell
authors.forename: Claire
authors.initials: C
authors.lastname: Durant
authors.forename: Alia
authors.initials: A
authors.lastname: Ataya
authors.forename: Chrysoula
authors.initials: C
authors.lastname: Papastathi
authors.forename: Ragini
authors.initials: R
authors.lastname: Bhake
authors.forename: Wolfram
authors.initials: W
authors.lastname: Woltersdorf
authors.forename: Stafford
authors.initials: S
authors.lastname: Lightman
mesh_terms: D002940:Circadian Rhythm; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008797:Metyrapone / Q000627:therapeutic use
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D006854:Hydrocortisone; D008797:Metyrapone
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