Yield of Serum Dexamethasone Measurement for Reducing False-Positive Results of Low-Dose Dexamethasone Suppression Testing

Author(s):  
Stephen M Roper

Abstract Background The low-dose dexamethasone suppression test (DST) using a cortisol cutoff of 1.8 µg/dL has approximate sensitivity of 95% and specificity of 80% for detecting Cushing syndrome. False-positive DST results can be caused by a variety of conditions, by low dexamethasone bioavailability, or by failure to take dexamethasone as instructed. In an effort to reduce false positives caused by low bioavailability or medication noncompliance, we evaluated the yield of serum dexamethasone measurement for identifying invalid results. Methods Data were queried for orders requesting concurrent measurement of serum cortisol and dexamethasone over a 41-month period. Inclusion criteria were serum cortisol and dexamethasone measured from the same specimen, specimen collection before 9 AM after 1 mg dexamethasone administration, and results for both analytes documented in the electronic medical record. Seventy paired measurements were identified with these criteria. Results were categorized into 4 groups based on observed cortisol and dexamethasone concentrations: (a) suppressed cortisol, low dexamethasone; (b) suppressed cortisol, therapeutic dexamethasone; (c) unsuppressed cortisol, low dexamethasone; or (d) unsuppressed cortisol, therapeutic dexamethasone. Results Overall, 35 (50%) results demonstrated suppressed cortisol and therapeutic dexamethasone levels. The next largest group was unsuppressed cortisol and therapeutic dexamethasone, representing approximately 32% (n = 22) of the study population. Ten result sets (14%) fell into the unsuppressed cortisol and low dexamethasone category, and 3 paired measurements (4%) fit the criteria for suppressed cortisol and low dexamethasone. Conclusions The measurement of serum dexamethasone following DST reduces the false-positive rate associated with subtherapeutic dexamethasone levels.

2017 ◽  
Vol 49 (11) ◽  
pp. 854-859
Author(s):  
Sandrine Urwyler ◽  
Nina Cupa ◽  
Mirjam Christ-Crain

AbstractIn this study, we compared the 2 mg dexamethasone suppression test (DST) with the gold-standard 1 mg DST in obese patients in order to reduce the false-positive rate for Cushing’s syndrome (CS). The primary endpoint was the comparison of serum cortisol levels after 1 mg versus 2 mg DST in patients with a BMI >30 kg/m2 and at least one additional feature of the metabolic syndrome. Secondary endpoints were comparison of salivary cortisol and ACTH levels, respectively. Fifty-four obese patients were included. Median serum cortisol levels after 1 mg DST and 2 mg DST were similar [28 nmol/l (20; 36) vs. 28 nmol/l (20; 38), p=0.53]. Salivary cortisol was 8.2 nmol/l (4.7; 11.7) after the 1 mg DST vs. 6.7 nmol/l (4.2; 9.5) after the 2 mg test, p=0.09. ACTH levels were higher after the 1 mg DST compared to the 2 mg DST [10.0 pg/ml (7.6; 10.7) vs. 5.0 pg/ml (5.0; 5.1), p<0.0001]. The false positive rate after the 1 mg DST was 14.8% (n=8) and was reduced to 11.1% (n=6) after the 2 mg DST. All non-suppressors (n=8) had type 2 diabetes and most of them took a medication interacting with cytochrome P450 3A4 (CYP3A4). In individuals with obesity, the 2 mg DST was not superior to the 1 mg DST in regard to serum cortisol levels. However, in some patients, particularly with poorly controlled diabetes or medication interacting with CYP3A4 and without adequate suppression after the 1 mg DST, the 2 mg DST might prove helpful to reduce the false-positive rate for CS. ClinicalTrials.gov Number: NCT02227420


BMJ ◽  
1985 ◽  
Vol 290 (6462) ◽  
pp. 158-159
Author(s):  
L. Kennedy ◽  
D. Hadden ◽  
B. Atkinson ◽  
B Sheridan ◽  
H. Johnston

2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Chen ◽  
Shi Chen ◽  
Lin Lu ◽  
Huijuan Zhu ◽  
Xiaobo Zhang ◽  
...  

ContextTraditionally, low-dose dexamethasone suppression test (LDDST) was used to confirm the diagnosis of Cushing’s syndrome (CS), and high-dose dexamethasone suppression test (HDDST) was used to differentiate Cushing’s disease (CD) and ectopic adrenocorticotropin (ACTH) syndrome (EAS), but some studies suggested that HDDST might be replaced by LDDST. For the differential diagnosis of CS, dexamethasone suppression test was usually combined with other tests such as bilateral petrosal sinus sampling (BIPSS) and pituitary magnetic resonance imaging, but the optimal pathway to incorporate these tests is still controversial.ObjectivesTo develop an optimized pathway for the differential diagnosis of CD and EAS based on LDDST.Design and SettingSingle-center retrospective study (2011–2019).PatientsTwo hundred sixty-nine CD and 29 EAS patients with pathological diagnosis who underwent consecutive low- and high-dose DST.ResultsFor the differential diagnosis of CD and EAS, the area under curve (AUC) of LDDST using urine free cortisol (0.881) was higher than that using serum cortisol (0.685) (p &lt; 0.001) in head-to-head comparison among a subgroup of 108 CD and 10 EAS. The AUC of LDDST (0.883) was higher than that of HDDST (0.834) among all the included patients. With the cutoff of &lt;26%, the sensitivity and specificity of LDDST were 39.4% and 100%. We designed a new pathway in which BIPSS was only reserved for those patients with unsuppressed LDDST and adenoma &lt;6mm, yielding an overall sensitivity of 97.7% and specificity of 86.7%.ConclusionLDDST had similar value to HDDST in differentiating CD and EAS using the specific cutoff point. The pathway that combined LDDST and BIPSS could differentiate CD and EAS accurately.


BMJ ◽  
1984 ◽  
Vol 289 (6453) ◽  
pp. 1188-1191 ◽  
Author(s):  
L Kennedy ◽  
A B Atkinson ◽  
H Johnston ◽  
B Sheridan ◽  
D R Hadden

2018 ◽  
Vol 50 (06) ◽  
pp. 453-461 ◽  
Author(s):  
Mona Mojtahedzadeh ◽  
Nesyah Shaesteh ◽  
Mastaneh Haykani ◽  
Jennifer Tran ◽  
Michael Mangubat ◽  
...  

AbstractWe 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.


2006 ◽  
Vol 91 (7) ◽  
pp. 2582-2586 ◽  
Author(s):  
N. M. Martin ◽  
W. S. Dhillo ◽  
A. Banerjee ◽  
A. Abdulali ◽  
C. N. Jayasena ◽  
...  

Abstract Context: The low-dose dexamethasone suppression test (LDDST) is widely used in confirming a diagnosis of Cushing’s syndrome. CRH administration at the end of an LDDST has been reported to improve the diagnostic accuracy of this test. Objective: Our objective was to assess whether CRH administration after a standard LDDST (LDDST-CRH test) improves diagnostic accuracy in Cushing’s syndrome. Design, Setting, and Participants: Thirty-six individuals with a clinical suspicion of Cushing’s syndrome each completed a standard LDDST and an LDDST-CRH test at Hammersmith Hospitals NHS Trust, London. The LDDST involved administration of 0.5 mg oral dexamethasone given 6-hourly for 48 h. Serum cortisol was measured 6 h after the last dose of dexamethasone, with a value of 50 nmol/liter or below excluding Cushing’s syndrome. Immediately after this, the LDDST-CRH test commenced with administration of a ninth dose of 0.5 mg dexamethasone. Exactly 2 h later, 100 μg human-sequence CRH was administered. Serum cortisol was measured 15 min after the CRH injection, with a value of less than 38 nmol/liter also excluding Cushing’s syndrome. Main Outcome Measure: Diagnosis or exclusion of Cushing’s syndrome was the main outcome measure. Results: Twelve subjects were diagnosed with Cushing’s syndrome (eight Cushing’s disease and four primary adrenal). The sensitivity of the LDDST in diagnosing Cushing’s syndrome was 100%, with a specificity of 88%. In contrast, although the sensitivity of the LDDST-CRH test was also 100%, specificity was reduced at 67%. These results give a positive predictive value of 80% for the LDDST and 60% for the LDDST-CRH test. Conclusion: This small study suggests that the addition of CRH to the LDDST does not improve the diagnostic accuracy of the standard LDDST in Cushing’s syndrome.


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