A novel prednisolone suppression test for the hypothalamic-pituitary-adrenal axis

• Published in: Biological psychiatry (1969) Vol. 51; no. 11; pp. 922 - 930
• Main Authors: Pariante, Carmine M, Papadopoulos, Andrew S, Poon, Lucia, Checkley, Stuart A, English, Judie, Kerwin, Robert W, Lightman, Stafford
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2002; Elsevier Science
• Subjects: Adult; Biological and medical sciences; Dexamethasone; Female; Fundamental and applied biological sciences. Psychology; glucocorticoid receptor; Glucocorticoids - metabolism; Hormones and neuropeptides. Regulation; Humans; Hydrocortisone - blood; Hydrocortisone - metabolism; Hypothalamo-Hypophyseal System - drug effects; Hypothalamus. Hypophysis. Epiphysis. Urophysis; Male; Middle Aged; mineralocorticoid receptor; Pituitary-Adrenal System - drug effects; Pituitary-Adrenal System - metabolism; plasma cortisol; Prednisolone - metabolism; Saliva - metabolism; salivary cortisol; Single-Blind Method; time-resolved immunofluorescent assay; Vertebrates: endocrinology; salivary cortisol; glucocorticoid receptor; Dexamethasone; mineralocorticoid receptor; plasma cortisol; time-resolved immunofluorescent assay; Corticosteroid; Healthy subject; Hypothalamohypophysoadrenal axis; Pathogenesis; Suppression; Anxiety disorder; Exploration; Cortisol; Method; Stress; Adrenal hormone; Hormonal investigation; Technique; Prednisolone; Hypothalamohypophysocorticoadrenal axis
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(01)01314-2

We have developed a suppressive test for the hypothalamic-pituitary-adrenal (HPA) axis using prednisolone, which is similar to endogenous glucocorticoids. We used a single-blind, repeated-measure design in healthy volunteers. In the first phase of the study, we compared placebo or prednisolone 2.5 mg, 5 mg, or 10 mg; in the second phase of the study, we compared placebo or prednisolone 5 mg or dexamethasone .5 mg. On the following day, we collected plasma and salivary cortisol levels from 9 am to 5 pm. Maximal average prednisolone plasma levels (at 9 am after the 10-mg dose) were 30 to 35 ng/mL. At all doses, prednisolone caused a larger suppression of salivary cortisol (approximately 20% after 2.5 mg, 30% to 35% after 5 mg, and 70% to 75% after 10 mg) than of plasma cortisol (approximately 5% after 2.5 mg, 10% after 5 mg, and 35% after 10 mg). Dexamethasone .5 mg gave 80% suppression of plasma cortisol and 90% suppression of salivary cortisol. Plasma and salivary cortisol levels were more consistently correlated in each subject after prednisolone than after dexamethasone. We propose that prednisolone at the 5-mg dosage (which gave partial HPA suppression), together with the assessment of salivary cortisol, can be used to investigate both impaired and enhanced glucocorticoid-mediated negative feedback in large samples of patients with psychiatric disorders.