J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York
An Update on the Overnight Dexamethasone Suppression Test for the Diagnosis of Cushing's Syndrome: Limitations in Patients with Mild and/or Episodic Hypercortisolism
Received: August 16, 2005
First decision: February 23, 2006
Accepted: March 16, 2006
16 August 2006 (online)
The overnight one-mg dexamethasone suppression test has been used for many years to screen for Cushing's syndrome. This test has usually been evaluated in controls versus patients with severe hypercortisolism. Under these conditions, the overnight dexamethasone suppression test has been reported to have high sensitivity and specificity. The objective of this study was to determine the sensitivity of the one mg overnight dexamethasone suppression test in patients with mild and/or periodic Cushing's syndrome. Therefore, an overnight dexamethasone suppression test was performed in 17 consecutive patients presenting to an endocrinology clinic with signs and symptoms of hypercortisolemia who were later proven to have Cushing's syndrome. The majority of patients were found to have both mild and periodic hypercortisolism. One mg of dexamethasone was given at midnight and a plasma cortisol was measured by radioimmunoassay at 08:00 the following morning. Using a cut-off for a morning cortisol following overnight dexamethasone of > 5 µg/dL, only three of 17 patients failed to suppress to a value less than this cut-off (sensitivity 18 %). A cut-off of > 2 µg/dL gave similar sensitivity. Even with a stringent cut-off point of > 1.8 µg/dL, only seven of 17 patients failed to suppress to a value less than this cut-off point (sensitivity of 41 %). These results demonstrate that the great majority of patients with mild and/or periodic Cushing's syndrome suppress to overnight dexamethasone. Since patients with mild and/or periodic Cushing's syndrome are the patients in whom the identification of hypercortisolism is difficult, our results from this relatively small study suggest that this test should no longer be used to exclude these patients from further workup for Cushing's syndrome.
Cushing's Syndrome - dexamethasone - hypercortisolism - episodic - periodic
- 1 Arnaldi G, Angeli A, Atkinson A B, Bertagna X, Cavagnini F, Chrousos G P, Fava G A, Findling J W, Gaillard R C, Grossman A B, Kola B, Lacroix A, Mancini T, Mantero F, Newell-Price J, Nieman L K, Sonino N, Vance M L, Giustina A, Boscaro M. Diagnosis and complications of Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab. 2003; 88 5593-5602
- 2 Asfeldt V H. Simplified dexamethasone suppression test. Acta Endocrinol (Copenh). 1969; 61 219-231
- 3 Blethen S L, Chasalow F I. Overnight dexamethasone suppression test: normal responses and the diagnosis of Cushing's syndrome. Steroids. 1989; 54 185-193
- 4 Connolly C K, Gore M B, Stanley N, Wills M R. Single-dose dexamethasone suppression in normal subjects and hospital patients. Br Med J. 1968; 2 665-667
- 5 Crapo L M. Cushing's syndrome: a review of diagnostic tests. Metab. 1979; 28 955-977
- 6 Cronin C, Igoe D, Duffy M J, Cunningham S K, McKenna T J. The overnight dexamethasone test is a worthwhile screening procedure. Clin Endocrinol (Oxf). 1990; 33 27-33
- 7 Findling J W, Raff H, Aron D C. The low-dose dexamethasone suppression test: a reevaluation in patients with Cushing's syndrome. J Clin Endocrinol Metab. 2004; 89 1222-1226
- 8 Foster L B, Dunn R T. Single-antibody technique for radioimmunoassay of cortisol in unextracted serum or plasma. Clin Chem. 1974; 20 365-368
- 9 Friedman T C.
Pseudo-Cushing syndrome.Margioris AN, Chrousos GP Contemporary Endocrinology: Adrenal Disorders. Totowa, NJ; Humana Press 2001: 203-218
- 10 Friedman T C.
The adrenal gland.Andreoli TE, Carpenter CCJ, Griggs RC, Loscalzo J Cecil Essentials of Medicine, 6th ed. Philadelphia; W. B. Saunders Company 2004: 603-614
- 11 Holdaway I M, Evans M C, Ibbertson H K. Experience with a short test of pituitary-adrenal function. Aust N Z J Med. 1973; 3 507-511
- 12 Isidori A M, Kaltsas G A, Mohammed S, Morris D G, Jenkins P, Chew S L, Monson J P, Besser G M, Grossman A B. Discriminatory value of the low-dose dexamethasone suppression test in establishing the diagnosis and differential diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 2003; 88 5299-5306
- 13 Liddle G W. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab. 1960; 20 1539-1561
- 14 McHardy-Young S, Harris P W, Lessof M H, Lyne C. Single dose dexamethasone suppression test for Cushing's Syndrome. Br Med J. 1967; 2 740-744
- 15 Mendlewicz J, Charles G, Franckson J M. The dexamethasone suppression test in affective disorder: relationship to clinical and genetic subgroups. Br J Psychiatry. 1982; 141 464-470
- 16 Montwill J, Igoe D, McKenna T J. The overnight dexamethasone test is the procedure of choice in screening for Cushing's syndrome. Steroids. 1994; 59 296-298
- 17 Nugent C A, Nichols T, Tyler F H. Diagnosis of Cushing's syndrome; single dose dexamethasone suppression test. Arch Intern Med. 1965; 116 172-176
- 18 Papanicolaou D A, Yanovski J A, Cutler Jr G, Chrousos G P, Nieman L K. A single midnight serum cortisol measurement distinguishes Cushing's syndrome from pseudo-Cushing states. J Clin Endocrinol Metab. 1998; 83 1163-1167
- 19 Pavlatos F C, Smilo R P, Forsham P H. A rapid screening test for Cushing's syndrome. JAMA. 1965; 193 720-723
- 20 Raff H, Raff J L, Findling J W. Late-night salivary cortisol as a screening test for Cushing's syndrome. J Clin Endocrinol Metab. 1998; 83 2681-2686
- 21 Seidensticker J F, Folk R L, Wieland R G, Hamwi G J. Screening test for Cushing's syndrome with plasma 11-hydroxycorticosteroids. JAMA. 1967; 202 87-90
- 22 Silber R H, Porter C C. The determination of 17, 21-dihydroxy-20-ketosteroids in urine and plasma. J Biol Chem. 1954; 210 923
- 23 Stewart P M.
The adrenal cortex.Larsen PR, Kronenberg HM, Melmed S, Polonsky KS Williams Textbook of Endocrinology, 10th ed. Philadelphia; Saunders 2003: 491-551
- 24 Thoren M, Sjoberg H E, Hall K, Low H. A rapid screening test for Cushing's syndrome. Acta Med Scand. 1975; 198 303-308
- 25 Tucci J R, Jagger P I, Lauler D P, Thorn G W. Rapid dexamethasone suppression test for Cushing's syndrome. JAMA. 1967; 199 379-382
- 26 Williams G H, Dhuly R G.
Disorders of the adrenal cortex.Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL Harrison's Principles of Internal Medicine, 15th ed. New York; McGraw-Hill 2001: 2084-2105
- 27 Wood P J, Barth J H, Freedman D B, Perry L, Sheridan B. Evidence for the low dose dexamethasone suppression test to screen for Cushing's syndrome-recommendations for a protocol for biochemistry laboratories. Ann Clin Biochem. 1997; 34 222-229
- 28 Yanovski J A, Cutler Jr G B, Chrousos G P, Nieman L K. Corticotropin-releasing hormone stimulation following low-dose dexamethasone administration: A new test to distinguish Cushing's syndrome from pseudo-Cushing's states. J Am Med Assoc. 1993; 269 2232-2238
M.D., Ph.D. Theodore C. Friedman
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