Comparison of 1 mg versus 2 mg Dexamethasone Suppression Test in Patients with Obesity

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

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.


1991 ◽  
Vol 36 (10) ◽  
pp. 746-748 ◽  
Author(s):  
D. Blake Woodside ◽  
Kathy Winter ◽  
Sandra Fisman

This study compares the paired serum and salivary Cortisol levels of 60 children and adolescents, obtained while performing a routine Dexamethasone Suppression Test. The results reveal significant correlations between serum and salivary cortisol levels in both drug-free (r = 0.90, p <.001) and medicated patients (r = 0.81, p < .0001). Multiple regression analysis suggests that, while the slopes of the two regression curves are parallel (0.15 < p < 0.20), the intercepts are significantly different (p < 0.05). This study supports the use of salivary measures of cortisol for children and adolescents. The authors suggest care in the use these measures while the patient is taking psychotropic medication.


2020 ◽  
Vol 17 (1) ◽  
pp. 13-21
Author(s):  
Zhanna E. Belaya ◽  
Anastasia A. Malygina ◽  
Tatiana A. Grebennikova ◽  
Aleksandr V. Il'yin ◽  
Liudmila Ya. Rozhinskaya ◽  
...  

BACKGROUND: Late-night salivary cortisol and serum cortisol measurements after 1-mg Dexamethasone Suppression Test (1-mg DST) are routinely used to diagnose Cushings syndrome (CS). Measuring morning salivary instead of serum cortisol after 1-mg DST would make the diagnostics of CS fully non-invasive. AIM: To evaluate the diagnostic accuracy of salivary cortisol in 1-mg DST as measured by electrochemiluminescence assay (ECLIA). MATERIALS AND METHODS: We combined a cohort diagnostic study, including 164 participants (132 females, 32 males) aged from 18 to 77 years: 110 were overweight or obese as increased BMI is the most common sign of Cushings Syndrome (CS), and 54 healthy volunteers. In each cohort late-night salivary cortisol was measured (at 23:00) followed by 1-mg DST and blood and salivary sampling for cortisol measurement the next morning at 08:00-09:00. Cortisol in saliva and serum were measured on automatic analyzer Cobas е 601 by F. Hoffmann-La Roche Ltd, using ECLIA. The final diagnosis was confirmed by the histological evaluation after surgery or using a follow-up observation in patients with obesity to exclude Cushings syndrome manifestation. RESULTS: Among 110 patients, 54 subjects were finally confirmed as having Cushing's syndrome. Reference interval for salivary cortisol after 1-mg DST was estimated to be 0,512,7 nmol/l (595 procentile). Maximal salivary cortisol level in 1-mg DST registered in healthy person was 29,6 mmol/l. Areas under the curve (AUC) were as following: for salivary cortisol in 1-mg DST 0,838 (95% СI 0,7720,905), for blood cortisol in 1-mg DST 0,965 (95% CI 0,9390,992) and for late-night salivary cortisol 0,925 (95% CI 0,8820,969). The optimal cut-off point for salivary cortisol after 1-mg DST was estimated as 12.1 nmol/l (sensitivity 60%, specificity 92,9%) among CS versus healthy subjects; 12,6 (sensitivity 58,2%, specificity 96,2%) among patients with obesity and CS; and 12,2 nmol/l (sensitivity 60,7%, specificity 93,4%) among CS and both obese and healthy control subjects. Considering small difference between cut-off points, the recommended cut-off value for salivary cortisol after 1-mg DST is recommended to be 12,0 nmol/l if measured by ECLIA. CONCLUSION: Although salivary cortisol after 1-mg DST is inferior to serum cortisol after 1-mg DST in the diagnostic performance and diagnostic accuracy, it can be used as a low-invasive screening test with superior specificity.


2003 ◽  
Vol 98 (5) ◽  
pp. 967-973 ◽  
Author(s):  
Joseph C. T. Chen ◽  
Arun P. Amar ◽  
SooHo Choi ◽  
Peter Singer ◽  
William T. Couldwell ◽  
...  

Object. Transsphenoidal adenomectomy with resection of a defined pituitary adenoma has been the treatment of choice for CD for the last 30 years. Surgical resection, however, may not always result in long-term remission of CD. This is particularly important in light of the high risk of morbidity and mortality in patients in the unsuccessfully treated cushingoid state. As such, it is interesting to identify prognostic factors that may predict the likelihood of long-term remission. Methods. The authors review their series of 174 patients who have undergone transsphenoidal procedures for CD over a period of 20 years with minimum follow-up periods of 5 years. Selection of these patients was based on clinical, imaging, and laboratory criteria that included serum cortisol levels, loss of diurnal variation in serum cortisol levels, urinary free cortisol concentration, and results of a dexamethasone suppression test, petrosal sinus sampling, and corticotroph-releasing hormone stimulation tests as indicated. All patients who met the biochemical criteria underwent transsphenoidal microsurgery. The authors found an overall rate of remission of 74% at 5 years postoperatively. Patients in whom morning serum cortisol concentrations were lower than 3 µg/dl (83 nmol/L) on postoperative Day 3, following an overnight dexamethasone suppression test, had a 93% chance of remission at the 5-year follow-up examination. Patients with cortisol concentrations higher than this level uniformly failed to achieve long-term remission. Conclusions. Transsphenoidal microsurgery is an effective means of control for patients with adrenocorticotrophic hormone—producing microadenomas. Clinical outcome correlated well with the size of the tumor, as measured on preoperative imaging studies, and with postoperative morning cortisol levels following an overnight dexamethasone suppression test. Postoperative cortisol levels can be used as a useful prognostic indicator of the likelihood of future recurrence following transsphenoidal adenomectomy in CD.


1986 ◽  
Vol 148 (1) ◽  
pp. 66-69 ◽  
Author(s):  
Howard Morris ◽  
Vaughan Carr ◽  
Judy Gilliland ◽  
Michael Hooper

The dexamethasone suppression test (DST) has been widely used in psychiatry as a laboratory aid for the diagnosis of endogenous depression; failure to suppress serum cortisol levels is interpreted as confirming a clinical diagnosis of endogenous depression. We found that serum dexamethasone concentrations in this test vary widely and are determinants of the DST response: non-suppression of serum cortisol levels is associated with low serum dexamethasone concentrations, and suppression is associated with high concentrations.


2017 ◽  
Vol 41 (1) ◽  
Author(s):  
Benjamin Sandner ◽  
Jürgen Kratzsch

AbstractBackground:The overnight dexamethasone suppression test (DST) is routinely used in establishing the diagnosis of Cushing’s syndrome. However, factors such as variable resorption and increased metabolism of dexamethasone (DXMS) could lead to false positive results. The aim of our study was to evaluate the influence of sex, body mass index (BMI) and age on the DXMS metabolism.Methods:In total, 183 subjects were enrolled in a regular 2 mg DST. Patients with Cushing’s syndrome, depression, renal or hepatic insufficiency and patients treated with liver enzyme modulating pharmaceuticals were excluded from this study, so that 72 patients and 66 healthy subjects were analyzed. Nocturnal blood withdrawals were performed in 11 adult subjects at 1:00 AM, 3:00 AM, 5:00 AM, 7:00 AM, 8:00 AM to evaluate the kinetic of DXMS and cortisol.Results:In the DST DXMS levels demonstrated a high variation at 8:00 AM, that was inversely correlated with BMI (r=−0.24, p=0.045). Furthermore, DXMS levels determined in patients with a BMI<30 kg/m2(n=29) were significantly higher than values of obese patients with a BMI>30 kg/m2(n=43) (1.66±0.71 ng/mL vs. 1.31±0.57 ng/mL, p=0.026). Cortisol levels, measured at the same time, were neither correlated with DXMS nor with BMI values. In the kinetic study, maximal DXMS concentration was measured at approximately 3:00 AM. At 8:00 AM, median of DXMS was reduced to 59.1% and was correlated directly with the DXMS AUC (r=0.75, p=0.013). However, there was no correlation between the cortisol levels at 8:00 AM and the nocturnal DXMS concentrations.Conclusions:In the DST BMI of individual patients could modulate the resorption rate and metabolism of DXMS but appears to have no impact on cortisol levels. Therefore, obesity should not be a cause of falsely positive results in the DST.


2017 ◽  
Vol 126 (02) ◽  
pp. 71-76
Author(s):  
Lele Li ◽  
Guoqing Yang ◽  
Jingtao Dou ◽  
Weijun Gu ◽  
Zhaohui Lv ◽  
...  

Abstract Introduction The cortisol/ACTH ratio was supposed to be helpful in the screening of subclinical hypercortisolism (SHC) in the published literatures. This study assessed the cortisol/ACTH ratio in patients with adrenal incidentaloma (AI) confirmed to have SHC and investigated its role for screening SCS in patients with AI. Methods This descriptive retrospective study included 183 patients with AIs [45 with SHC and 138 with non-functional adenoma (NFA)]. Cortisol and ACTH levels were measured at 8:00, 16:00, and 0:00, and the cortisol/ACTH ratio was calculated. ROC curve was used to evaluate efficacy of the cortisol/ACTH ratio, explore the best cut-off value and its corresponding sensitivity and specificity. Results The cortisol/ACTH ratios at all time points were significantly higher in the SHC group than the NFA group (P<0.05) and were significantly correlated with serum cortisol levels after the 1-mg dexamethasone suppression test (DST). Area Under the Curve (AUC) of the cortisol/ACTH ratio at 0:00 and midnight serum cortisol levels were 0.893 (0.843–0.943) and 0.831 (0.765–0.806), respectively. A cortisol/ACTH ratio at 0:00 cut-off of 32.18 nM/pM showed a sensitivity of 100% and specificity of 39.1%. The optimal cut-off was 68.83 nM/pM (sensitivity 86.7%, specificity 75.4%). Conclusions Patients with SHC have a higher cortisol/ACTH ratio than those with NFAs. The cortisol/ACTH ratio is significantly correlated with serum cortisol after the 1-mg DST. The diagnostic performance of the cortisol/ACTH ratio at 0:00 is superior to midnight serum cortisol. Therefore, the cortisol/ACTH ratio at 0:00 may be a reliable parameter for SHC screening in patient with AI.


1998 ◽  
Vol 13 (8) ◽  
pp. 411-418 ◽  
Author(s):  
C Massoubre ◽  
F Lang ◽  
L Millot ◽  
M Pichon ◽  
B Estour ◽  
...  

SummaryThis study was conducted to investigate the corticotropic axis in anorexia nervosa. In 93 female inpatients who met DSM-III-R criteria for anorexia nervosa, subsample (n = 64) with DSM-III criteria was also considered. Using stepwise regression analysis, this study examined the relationship between independent variables ie, age, body mass index, scores on depression scales and postdexamethasone serum cortisol, considered as a dependent variable. In patients who met DSM-III criteria, 16.7% of the variance of serum cortisol can be explained. The main predictors are depressive retardation, emaciation and age. Using stepwise logistic regression the main categorical predictors of the test suppression vs non suppression are of the same nature. The condition of realisation of DST are discussed.


Author(s):  
Natalia Genere ◽  
Ravinder Jeet Kaur ◽  
Shobana Athimulam ◽  
Melinda A Thomas ◽  
Todd Nippoldt ◽  
...  

Abstract Context Interpretation of dexamethasone suppression test (DST) may be influenced by dexamethasone absorption and metabolism and by the altered cortisol binding Objective We aimed to determine the normal ranges of free cortisol during DST in participants without adrenal disorders, and to identify the population of patients where post-DST free cortisol measurements add value to the diagnostic work up. Design and Setting Cross-sectional study conducted in a tertiary medical center Participants Adult volunteers without adrenal disorders (n=168; 47 women on oral contraceptive therapy (OCP), 66 women not on OCP, 55 men) and patients undergoing evaluation for hypercortisolism (n=196; 16 women on OCP) Measurements Post-DST dexamethasone and free cortisol (mass spectrometry) and total cortisol (immunoassay). Main Outcome Measures Reference range for post-DST free cortisol, diagnostic accuracy of post-DST total cortisol. Results Adequate dexamethasone concentrations (≥0.1 mcg/dL) were seen in 97.6% volunteers and 96.3% patients. Only 25.5% of women volunteers on OCP had abnormal post-DST total cortisol (&gt;1.8 mcg/dL). In volunteers, the upper post-DST free cortisol range was 48 ng/dL in men and women not on OCP, and 79 ng/dL in women on OCP. When compared to post-DST free cortisol, diagnostic accuracy of post-DST total cortisol was 87.3% (95%CI 81.7-91.7); all false positive results occurred in patients with post-DST cortisol between 1.8 and 5 mcg/dL. OCP use was the only factor associated with false positive results (21.1% vs 4.9%, p=0.02). Conclusions Post-DST free cortisol measurements are valuable in patients with optimal dexamethasone concentrations and post-DST total cortisol between 1.8 and 5 mcg/dL.


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