Low-Dose and Standard Overnight and Low Dose-Two Day Dexamethasone Suppression Tests in Patients with Mild and/or Episodic Hypercortisolism

Mona Mojtahedzadeh; Nesyah Shaesteh; Mastaneh Haykani; Jennifer L. A. Tran; Michael Mangubat; Hraya K. Shahinian; Rahul Nachnani; Mohan Zopey; Jason Saidian; Antolice Thomas; Martin L. Lee; Ian E. McCutcheon; Theodore C. Friedman

doi:10.1055/a-0603-3868

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(06): 453-461
DOI: 10.1055/a-0603-3868

Endocrine Care

Low-Dose and Standard Overnight and Low Dose-Two Day Dexamethasone Suppression Tests in Patients with Mild and/or Episodic Hypercortisolism

Mona Mojtahedzadeh

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Nesyah Shaesteh

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Mastaneh Haykani

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Jennifer L. A. Tran

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Michael Mangubat

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Hraya K. Shahinian

²Skull Base Institute, Los Angeles, CA, USA

,

Rahul Nachnani

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Mohan Zopey

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Jason Saidian

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Antolice Thomas

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Martin L. Lee

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

,

Ian E. McCutcheon

³Department of Neurosurgery, MD Anderson Medical Center, Houston TX, USA

,

Theodore C. Friedman

¹Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA

› Author Affiliations

Abstract

We previously reported on the lack of utility of the 1 mg overnight dexamethasone (DEX) test in mild and/or periodic Cushing’s syndrome, as most patients with the condition suppressed to 1 mg DEX. It is possible that a lower dose of DEX as part of an overnight DEX test might be able to distinguish between mild and/or periodic Cushing’s syndrome and those without the condition. The objective of the current study is to determine the sensitivity and specificity of a 0.25 mg overnight DEX suppression test, the standard 1 mg overnight DEX suppression test, and the two-day low-dose (Liddle test) DEX suppression test with and without correction for DEX levels in patients evaluated for mild and/or periodic Cushing’s syndrome. Thirty patients determined to have Cushing’s syndrome by biochemical testing and 14 patients determined not to have the condition had the 0.25 mg and standard 1 mg overnight DEX suppression test and the two-day low-dose DEX suppression tests. Our results show that morning serum cortisol and cortisol/DEX ratios following an overnight dexamethasone suppression test were similar in patients with Cushing’s syndrome and those not having Cushing’s syndrome. However, a morning cortisol value above 7.6 μg/dl following a dose of DEX of 0.25 mg was found in 12 patients with Cushing’s syndrome and none in those not having Cushing’s syndrome, suggesting that a high cortisol value after this low dose of dexamethasone can indicate that further testing for Cushing’s syndrome is warranted. Our data suggest that the traditional 1 mg overnight or the 2 mg/2 day DEX suppression testing should no longer be used as a screening test in patients who could have mild and/or periodic Cushing’s syndrome, while the 0.25 mg dose of DEX may pick up some patients with mild Cushing’s syndrome.

Key words

Cushing’s syndrome - cortisol - hypercortisolism - episodic - periodic

Full Text

References

References
1 Liddle GW. Tests of pituitary-adrenal suppressibility in the diagnosis of Cushing's syndrome. J Clin Endocrinol Metab 1960; 20: 1539-1561
2 Nugent CA, Nichols T, Tyler FH. Diagnosis of Cushing's syndrome; single dose dexamethasone suppression test. Arch Intern Med 1965; 116: 172-176
3 Pavlatos FC, Smilo RP, Forsham PH. A rapid screening test for Cushing's syndrome. JAMA 1965; 193: 720-723
4 Thoren M, Sjoberg HE, Hall K, Low H. A rapid screening test for Cushing's syndrome. Acta Med Scand 1975; 198: 303-308
5 Connolly CK, Gore MB, Stanley N, Wills MR. Single-dose dexamethasone suppression in normal subjects and hospital patients. Br Med J 1968; 2: 665-667
6 Tucci JR, Jagger PI, Lauler DP, Thorn GW. Rapid dexamethasone suppression test for Cushing's syndrome. JAMA 1967; 199: 379-382
7 Asfeldt VH. Simplified dexamethasone suppression test. Acta Endocrinol (Copenh) 1969; 61: 219-231
8 Holdaway IM, Evans MC, Ibbertson HK. Experience with a short test of pituitary-adrenal function. Aust N Z J Med 1973; 3: 507-511
9 McHardy-Young S, Harris PW, Lessof MH, Lyne C. Single dose dexamethasone suppression test for Cushing's Syndrome. Br Med J 1967; 2: 740-744
10 Seidensticker JF, Folk RL, Wieland RG, Hamwi GJ. Screening test for Cushing's syndrome with plasma 11-hydroxycorticosteroids. JAMA 1967; 202: 87-90
11 Montwill J, Igoe D, McKenna TJ. The overnight dexamethasone test is the procedure of choice in screening for Cushing's syndrome. Steroids 1994; 59: 296-298
12 Cronin C, Igoe D, Duffy MJ, Cunningham SK, McKenna TJ. The overnight dexamethasone test is a worthwhile screening procedure. Clin Endocrinol (Oxf) 1990; 33: 27-33
13 Wood PJ, Barth JH, Freedman DB, 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
14 Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, Montori VM. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93: 1526-1540
15 Friedman TC, Ghods DE, Shahinian HK, Zachery L, Shayesteh N, Seasholtz S, Zuckerbraun E, Lee ML, McCutcheon IE. High prevalence of normal tests assessing hypercortisolism in subjects with mild and episodic Cushing's syndrome suggests that the paradigm for diagnosis and exclusion of Cushing's syndrome requires multiple testing. Horm Metab Res 2010; 42: 874-881
16 Friedman TC. An update on the overnight dexamethasone suppression test for the diagnosis of Cushing's syndrome: limitations in patients with mild and/or episodic hypercortisolism. Exp Clin Endocrinol Diabetes 2006; 114: 356-360
17 Friedman TC. Pseudo-Cushing syndrome. In: Margioris AN, Chrousos GP. eds Contemporary Endocrinology: Adrenal Disorders. Totowa, NJ: Humana Press; 2001: 203-218
18 Pall ME, Lao MC, Patel SS, Lee ML, Ghods DE, Chandler DW, Friedman TC. Testosterone and bioavailable testosterone help to distinguish between mild cushing's syndrome and polycystic ovarian syndrome. Horm Metab Res 2008; 40: 813-818
19 Pikkarainen L, Alfthan H, Markkanen H, Sane T. Midnight serum cortisol: Comparison of healthy volunteers and hospitalized patients with Cushing's syndrome. Scand J Clin Lab Invest 2002; 62: 357-360
20 Burke CW. Biologically active cortisol in plasma of oestrogen-treated and normal subjects. Br Med J 1969; 2: 798-800
21 Doe RP, Zinneman HH, Flink HB, Ulstrom RA. Significance of the concentration of non protein bound plasma cortisol in normal subjects, Cushing's syndrome, pregnancy and during estrogen therapy. J Clin Endocrinol Metab 1960; 20: 1484-1492
22 Meeran K, Hattersley A, Mould G, Bloom SR. Venepuncture causes rapid rise in plasma ACTH. Br J Clin Pract 1993; 47: 246-247
23 Oldfield EH, Doppman JL, Nieman LK, Chrousos GP, Miller DL, Katz DA, Cutler Jr. GB, Loriaux DL. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing's syndrome. N Engl J Med 1991; 325: 897-905
24 Valassi E, Swearingen B, Lee H, Nachtigall LB, Donoho DA, Klibanski A, Biller BM. Concomitant medication use can confound interpretation of the combined dexamethasone-corticotropin releasing hormone test in Cushing's syndrome. J Clin Endocrinol Metab 2009; 94: 4851-4859
25 Esoterix Laboratory Sciences. Cortisol By HPLC with Mass Spectrometry. 2006; Test # 803990
26 Esoterix Laboratory Sciences. Dexamethasone. 2007; Test # 500140
27 [Anonymous]. In: https://esoterix.com/sites/esoterix/files/L5167.pdf
28 Silber RH, Porter CC. The determination of 17,21-dihydroxy-20-ketosteroids in urine and plasma. J Biol Chem 1954; 210: 923-932
29 DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics 1988; 44: 837-845
30 Meikle AW. Dexamethasone suppression tests: Usefulness of simultaneous measurement of plasma cortisol and dexamethasone. Clin Endocrinol (Oxf) 1982; 16: 401-408
31 Findling JW, Raff H, Aron DC. The low-dose dexamethasone suppression test: A reevaluation in patients with Cushing's syndrome. J Clin Endocrinol Metab 2004; 89: 1222-1226
32 Chriguer RS, Elias LL, da Silva Jr. IM, Vieira JG, Moreira AC, de Castro M. Glucocorticoid sensitivity in young healthy individuals: In vitro and in vivo studies. The Journal of Clinical Endocrinology and Metabolism 2005; 90: 5978-5984
33 Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, Grobbee DE, Brinkmann AO, De Jong FH, Lamberts SW. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab 1998; 83: 144-151

Supplementary Material

Supplementary Material