Advertisement
Techniques and methods| Volume 51, ISSUE 11, P922-930, June 01, 2002

Download started.

Ok

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

      Abstract

      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.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Ballard P.L
        • Carter J.P
        • Graham B.S
        • Baxter J.D
        A radioreceptor assay for evaluation of the plasma glucocorticoid activity of natural and synthetic steroid in man.
        J Clin Endocrinol Metab. 1975; 41: 290-304
        • Bearn J
        • Buntwal N
        • Papadopoulos A.S
        • Checkey S.A
        Salivary cortisol during opiate dependence and withdrawal.
        Addict Biol. 2001; 6: 157-162
        • Bossuyt X
        • Muller M
        • Hagenbuch B
        • Meier P.J
        Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver.
        J Pharmacol Exp Ther. 1996; 276: 891-896
        • Cassidy F
        • Ritchie J.C
        • Verghese K
        • Carroll B.J
        Dexamethasone metabolism in dexamethasone suppression test suppressors and nonsuppressors.
        Biol Psychiatry. 2000; 47: 677-680
        • Chakraborty J
        • English J
        • Marks V
        • Dumasia M.C
        • Chapman D.J
        A radioimmunoassay method for prednisolone.
        Br J Clin Pharmacol. 1976; 3: 903-906
        • De Kloet E.R
        • Vreugdenhil E
        • Oitzl M.S
        • Joels M
        Brain corticosteroid receptor balance in health and disease.
        Endocr Rev. 1998; 19: 269-301
        • Dressendorfer R.A
        • Kirschbaum C
        • Rohde W
        • Stahl F
        • Strasburger C.J
        Synthesis of a cortisol-biotin conjugate and evaluation as a tracer in an immunoassay for salivary cortisol measurement.
        J Steroid Biochem Molec Biol. 1992; 43: 683-692
        • Ebrecht M
        • Buske-Kirschbaum A
        • Hellhammer D
        • Kern S
        • Rohleder N
        • Walker B
        • Kirschbaum C
        Tissue specificity of glucocorticoids sensitivity in healthy adults.
        J Clin Endocrinol Metab. 2000; 85: 3733-3739
        • Gold P.W
        • Goodwin F.K
        • Chrousos G.P
        Clinical and biochemical manifestation of depression. Relation to the neurobiology of stress.
        N Engl J Med. 1988; 319 (413–420): 348-353
        • Hansen-Grant S
        • Pariante C.M
        • Kalin N
        • Miller A.H
        Neuroendocrine and immune system pathology in psychiatry disease.
        in: Schatzberg A.F Nemeroff C.B Textbook of Psychopharmacology. 2nd ed. American Psychiatric Press, Washington, DC1998: 171-194
        • Harris B
        • Cook N
        • Warner N
        • Read G.F
        • Walker R.F
        • Thomas R
        • Riad-Fahmy D
        Anxiety and the dexamethasone suppression test monitored with saliva.
        Biol Psychiatry. 1988; 23: 698-704
        • Harris B
        • Watkins S
        • Cook N
        • Walker R.F
        • Read G.F
        • Riad-Fahmy D
        Comparisons of plasma and salivary cortisol determination for the diagnostic efficacy of the dexamethasone suppression test.
        Biol Psychiatry. 1990; 27: 897-904
        • Heim C
        • Ehlert U
        • Hanker J.P
        • Hellhammer D.K
        Abuse-related stress disorder and alteration of the hypothalamic-pituitary-adrenal axis in women with chronic pelvic pain.
        Psychosom Med. 1998; 60: 309-318
        • Heim C
        • Ehlert U
        • Hellhammer D.H
        The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorder.
        Psychoneuroendocrinology. 2000; 25: 1-35
        • Holsboer F
        The corticosteroids receptor hypothesis of depression.
        Neuropsychopharmacology. 2000; 23: 477-501
        • Kahn J.P
        • Rubinow D.R
        • Davis C.L
        • Kling M
        • Post R.M
        Salivary cortisol.
        Biol Psychiatry. 1988; 23: 335-349
        • Karssen A.M
        • Meijer O.C
        • Van Der Sandt I.C.J
        • Lucassen P.J
        • De Lange E.C.M
        • De Boer A.G
        • De Kloet E.R
        Multidrug resistance p-glycoprotein hampers the access of cortisol but not corticosterone to mouse and human brain.
        Endocrinology. 2001; 142: 2686-2694
        • Kellner M
        • Yehuda R
        Do panic disorder and posttraumatic stress disorder share a common psychoneuroendocrinology?.
        Psychoneuroendocrinology. 1999; 24: 485-504
        • Kirschbaum C
        • Hellhammer D.H
        Salivary cortisol in psychoneuroendocrine research.
        Psychoneuroendocrinology. 1994; 19: 313-333
        • Lac G
        • Marquet P
        • Chassain A.P
        • Galen F.X
        Dexamethasone in resting and exercising men. II. Effects on adrenocortical hormones.
        J Appl Physiol. 1999; 87: 183-188
        • Lan N.C
        • Graham B
        • Bartter F.C
        • Baxter J.D
        Binding of steroids to mineralocorticoid receptors.
        J Clin Endocrinol Metab. 1982; 54: 332-342
        • Lan N.C
        • Matulich D.T
        • Morris J.A
        • Baxter J.D
        Mineralocorticoid receptor-like aldosterone-binding protein in cell culture.
        Endocrinology. 1981; 109: 1963-1970
        • Liddle G.W
        Studies of structure-function relationships of steroids. II. The 6-alpha-methylcorticosteroids.
        Metabolism. 1958; 7: 405-415
        • Nakayama A
        • Eguchi O
        • Hatakeyama M
        • Saitoh H
        • Takada M
        Different absorption among steroid hormones due to possible interaction with p-glycoprotein in the rat small intestine.
        Biol Pharm Bull. 1999; 22: 535-538
        • Nemeroff C.B
        The corticotropin-releasing factor (CRF) hypothesis of depression.
        Mol Psychiatry. 1996; 1: 336-342
        • Orth D.N
        • Kovacs W.J
        The adrenal cortex.
        in: Wilson J.D Foster D.W Kronenberg H.M Larsen P.R Williams Textbook of Endocrinology. 9th ed. W.B. Saunders, Philadelphia1998: 517-664
        • Pariante C.M
        • Makoff A
        • Lovestone S
        • Feroli S
        • Heyden A
        • Miller A.H
        • Kerwin R.W
        Antidepressants enhance glucocorticoid receptor function in vitro by modulating the membrane steroid transporter.
        Br J Pharmacol. 2001; 134: 1335-1343
        • Pariante C.M
        • Miller A.H
        Glucocorticoid receptors in major depression.
        Biol Psychiatry. 2001; 49: 391-404
        • Pariante C.M
        • Pearce B.D
        • Pisell T.L
        • Owens M.J
        • Miller A.H
        Steroid-independent translocation of the glucocorticoid receptor by the antidepressant desipramine.
        Mol Pharmacol. 1997; 52: 571-581
        • Pariante C.M
        • Pearce B.D
        • Pisell T.L
        • Su C
        • Miller A.H
        The steroid receptor antagonists, RU486 and RU40555, activate glucocorticoid receptor translocation and are not excreted by the steroid hormone transporter in L929 cells.
        J Endocrinology. 2001; 169: 309-320
        • Pugeat M.M
        • Dunn J.F
        • Nisula B.C
        Transport of steroid hormones.
        J Clin Endocrinol Metab. 1981; 53: 69-75
        • Reul J.M.H.M
        • Gesing A
        • Droste S
        • Stec I.S.M
        • Weber A
        • Bachmann C
        • et al.
        The brain mineralocorticoid receptor.
        Eur J Pharmacol. 2000; 405: 235-249
        • Reynolds R.M
        • Bendall H.E
        • Whorwood C.B
        • Wood P.J
        • Walker B.R
        • Phillips D.I.W
        Reproducibility of the low dose dexamethasone suppression test.
        Clin Endocrinol. 1998; 49: 307-310
        • Ribeiro S.C.M
        • Tandon R
        • Grunhaus L
        • Greden J.F
        The DST as a predictor of outcome in depression.
        Am J Psychiatry. 1993; 150: 1618-1629
        • Ritzi E.M
        Quantitative flow cytometry reveals a hierarchy of glucocorticoid effect on cell surface mouse mammary tumor virus gp52.
        J Steroid Biochem Molec Biol. 1996; 57: 33-42
        • Rohatagi S
        • Barth J
        • Mollmann H
        • Hochhaus G
        • Soldner A
        • Mollmann C
        • Derendorf H
        Pharmacokinetics of methylprednisolone and prednisolone after single and multiple oral administration.
        J Clin Pharmacol. 1997; 37: 916-925
        • Rupprecht R
        • Reul J.M.H.M
        • van Steensel B
        • Spengler D
        • Soder M
        • Berning B
        • et al.
        Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands.
        Eur J Pharmacol. 1993; 247: 145-154
        • Seidegard J
        • Simonsson M
        • Edsbacker S
        Effects of an oral contraceptive on the plasma levels of budesonide and prednisolone and the influence on plasma cortisol.
        Clin Pharmacol Ther. 2000; 67: 373-381
        • Slater J.D.H
        • Heffron P.F
        • Vernet A
        • Nabarro J.D.N
        Clinical and metabolic effects of dexamethasone.
        Lancet. 1959; 1: 173-177
        • Stein M.B
        • Yehuda R
        • Koverola C
        • Hanna C
        Enhanced dexamethasone suppression test of plasma cortisol in adult women traumatized by childhood sexual abuse.
        Biol Psychiatry. 1997; 42: 680-686
        • Tanaka H
        • Hirano F
        • Nomura Y
        • Miura T
        • Makino Y
        • Fukawa E
        • Makino I
        Relative glucocorticoid potency revisited.
        Rheumatol Int. 1994; 14: 9-12
        • Ueda K
        • Okamura N
        • Hirai M
        • Tanigawara Y
        • Saeki T
        • Kioka N
        • et al.
        Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.
        J Biol Chem. 1992; 267: 24248-24252
        • Yehuda R
        • Boisoneau D
        • Lowy M.T
        • Giller Jr, E.L
        Dose-response changes in plasma cortisol and lymphocyte glucocorticoid receptors following dexamethasone administration in combat veterans with and without posttraumatic stress disorder.
        Arch Gen Psychiatry. 1995; 52: 583-593
        • Yehuda R
        • Giller E.L
        • Southwick S.M
        • Lowy M.T
        • Mason J.W
        Hypothalamic-pituitary-adrenal dysfunction in posttraumatic stress disorder.
        Biol Psychiatry. 1991; 30: 1031-1048
        • Young E.A
        • Haskett R.F
        • Murphy-Weinberg V
        • Watson S.J
        • Akil H
        Loss of glucocorticoid fast feedback in depression.
        Arch Gen Psychiatry. 1991; 48: 693-699