Interpretation of Abnormal Dexamethasone Suppression Test is Enhanced With Use of Synchronous Free Cortisol Assessment

2021 ◽  
Author(s):  
Natalia Genere ◽  
Ravinder Jeet Kaur ◽  
Shobana Athimulam ◽  
Melinda A Thomas ◽  
Todd Nippoldt ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
False Positive ◽  
Medical Center ◽  
Dexamethasone Suppression Test ◽  
Total Cortisol ◽  
Normal Ranges ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Positive Results

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 (>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.

Abstract #130 Diagnostic Accuracy of Dexamethasone Suppression Test: Additive Value of Free Cortisol and Dexamethasone Measurements

2019 ◽  
Vol 25 ◽  
pp. 19
Author(s):  
Ravinder Jeet Kaur ◽  
Shobana Athimulam ◽  
Molly Van Norman ◽  
Melinda Thomas ◽  
Stefan K. Grebe ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Dexamethasone Suppression Test ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

scholarly journals Elevated Testosterone Levels With Unclear Etiology- the Need for Longer Follow up and Role of Dexamethasone Suppression Test as a Useful Tool to Distinguish Tumorous vs Non Tumorous Etiology

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A757-A758
Author(s):  
Muhammad Ilyas Khan ◽  
Stuart Ruthven ◽  
Peter Smith ◽  
Monika Oktaba ◽  
Sumer A ◽  
...  
Keyword(s):  
Testosterone Level ◽  
Low Dose ◽  
Dexamethasone Suppression Test ◽  
Bilateral Oophorectomy ◽  
Testosterone Levels ◽  
Free Cortisol ◽  
Suppression Test ◽  
Unclear Etiology ◽  
Dexamethasone Suppression

Abstract Background: Severe hirsutism in women in conjunction with elevated testosterone level raises concern for androgen secreting tumors. When initial investigations and radiological imaging do not identify a tumorous pathology, clinicians are faced with a dilemma on whether to investigate further or to consider a benign cause such as PCOS or ovarian hyperthecosis. There is inadequate evidence on how long these patients need to be followed up before considering a benign cause for their symptoms. Clinical Case: 57 years-old female, with pertinent history including primary hypothyroidism and eczema, was referred to endocrine clinic in September-2011 for work-up of severe hirsutism and elevated testosterone levels of 4.1 nmol /L (n: 0 - 2.5). All other tests including androstenedione, DHEAS, baseline pituitary profile and 24-hours urinary free cortisol levels were unremarkable. MRI of adrenal glands and ovaries was also unremarkable. Patient was presumptively diagnosed with ovarian hyperthecosis and commenced on spironolactone. There was improvement in hirsutism and patient was discharged from clinic in Feb 2012. Patient was re-referred to endocrine clinic 7 years later in September-2019 for worsening of hirsutism, male pattern baldness. At this stage, patient had testosterone levels of 17– 23 nmol/L (n: 0 - 2.5). Free androgen index 76.6% (n:0–7), SHBG (35 nmol/L, n: 18 – 114). Androstenedione (4 nmol, n: 1 – 8.5) DHEAS (2.3 umol/L, n: 0.3 – 12), 24-hours urine free cortisol level (< 13 nmol, n: < 165 nmol), 17-hydroxyprogesterone, serum ACTH, TSH, LH and FSH and estradiol levels were all normal. On examination patient had signs of virilization which had developed over previous six months. Patient had a low dose dexamethasone suppression test (0.5 mg of dexamethasone 6 hourly for 48 hours). The androgen profile obtained pre and post test showed no suppression in testosterone but well suppressed cortisol. Patient had repeat MRI of the adrenals and ovaries which revealed focal enhancing mass in right ovary (3.3 x 2.5 x 2.6 cm). Patient had an urgent bilateral oophorectomy and histology confirmed a rare steroid cell tumour of the right ovary. Following surgery there has been a significant improvement in her symptoms. Conclusion: Patients with elevated testosterone level and unclear etiology need longer follow up and review of investigations when symptoms worsen as yet undiscovered sinister etiology could be the likely reason. Dexamethasone suppression can be considered as a useful tool to distinguish tumorous vs non tumorous etiology in early stage of investigations as poor suppression of androgens with dexamethasone increases the likelihood of tumorous etiology1References: 1. Kaltsas GA, Isidori AM, Kola BP, et al. The Value of the Low-Dose Dexamethasone Suppression Test in the Differential Diagnosis of Hyperandrogenism in Women. The Journal of Clinical Endocrinology & Metabolism 2003; 88(6): 2634-43.

How early can one diagnose Cushing’s disease? An early diagnosis in a case of prepubertal Cushing’s disease

2014 ◽  
Vol 27 (11-12) ◽  
pp. 1043-1047 ◽  
Author(s):  
Julia Hoppmann ◽  
Isabel V. Wagner ◽  
Gudrun Junghans ◽  
Stefan A. Wudy ◽  
Michael Buchfelder ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Cushing’S Disease ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
High Dose ◽  
Thyroid Function Tests ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

Abstract Background: Cushing’s disease is very rare in children, and the diagnosis is frequently delayed by several years. Objective: We report a case of prepubertal Cushing’s disease with a medical history of only 9 months. This case illustrates the difficulties involved in diagnosing children at the early stage of the disease. Case presentation: An 8-year-old prepubertal boy presented with rapid weight gain accompanied by a decreasing growth velocity and hirsutism. Thyroid function tests and growth factor levels were normal, thus excluding hypothyroidism and growth hormone deficiency. Cushing’s syndrome was confirmed by elevated 24-h urinary free cortisol levels, increased diurnal cortisol levels, and a lack of cortisol suppression in the low-dose dexamethasone suppression test. Further tests to investigate the source of the hypercortisolism showed the following results: Basal morning adrenocorticotropic hormone (ACTH) was normal. The high-dose dexamethasone suppression test led to a 51% decrease in cortisol level. In the corticotropin-releasing hormone (CRH) test, ACTH and cortisol increased only by 28%. Repeated magnetic resonance imaging (MRI) finally revealed a microadenoma in the anterior pituitary, thus establishng the diagnosis of Cushing’s disease. Upon diagnosis, the patient underwent transsphenoidal surgery. Histological analysis confirmed an ACTH-secreting pituitary adenoma. Conclusion: This case illustrates the difficulties associated with the clinical, biochemical, and radiological diagnoses of Cushing’s disease in children. Early diagnosis remains a challenge because test results often do not match standard diagnostic criteria.

scholarly journals Clinical Characteristics of Endogenous Cushing’s Syndrome at a Medical Center in Southern Taiwan

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Shih-Chen Tung ◽  
Pei-Wen Wang ◽  
Rue-Tsuan Liu ◽  
Jung-Fu Chen ◽  
Ching-Jung Hsieh ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cushing’S Syndrome ◽  
Plasma Cortisol ◽  
Medical Center ◽  
Cushing's Syndrome ◽  
Dexamethasone Suppression Test ◽  
Adrenocortical Adenoma ◽  
Suppression Test ◽  
Southern Taiwan ◽  
Dexamethasone Suppression

From January 1987 to December 2011, over a total of 25 years, 84 patients with Cushing’s syndrome (CS) were identified at a medical center in southern Taiwan. We observed a higher incidence of ACTH-independent CS (75%) than ACTH-dependent CS (25%). A higher incidence of adrenocortical adenoma (58.3%) than Cushing’s disease (CD, 21.4%) was also found. The sensitivity of the definitive diagnostic tests for CS, including loss of plasma cortisol circadian rhythm, a baseline 24 h urinary free cortisol (UFC) value >80 μg, and overnight and 2-day low-dose dexamethasone suppression test, was between 94.4% and 100%. For the 2-day high-dose dexamethasone suppression test for the differential diagnosis of CD, the sensitivity of 0800 h plasma cortisol and 24 h UFC was 44.4% and 85.7%, respectively. For the differential diagnosis of adrenal CS, the sensitivities of the 0800 h plasma cortisol and 24 h UFC were 95.5% and 88.9%, respectively. In patients with ACTH-independent CS and ACTH-dependent CS, the baseline plasma ACTH levels were all below 29 pg/mL and above 37 pg/mL, respectively. The postsurgical hospitalization stay following retroperitoneoscopic adrenalectomy was shorter than that observed for transabdominal adrenalectomy (4.3 ± 1.6 versus 8.8 ± 3.7 days,P<0.001). It was easy to develop retroperitoneal and peritoneal seeding of adrenocortical carcinoma via laparoscopic adrenalectomy.

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
Keyword(s):  
Salivary Cortisol ◽  
False Positive ◽  
False Positive Rate ◽  
Serum Cortisol ◽  
Dexamethasone Suppression Test ◽  
Obese Patients ◽  
Positive Rate ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

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

scholarly journals An Optimized Pathway for the Differential Diagnosis of ACTH-Dependent Cushing’s Syndrome Based on Low-Dose Dexamethasone Suppression Test

2021 ◽  
Vol 12 ◽  
Author(s):  
Kang Chen ◽  
Shi Chen ◽  
Lin Lu ◽  
Huijuan Zhu ◽  
Xiaobo Zhang ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cushing’S Syndrome ◽  
Low Dose ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Dexamethasone Suppression Test ◽  
High Dose ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

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.

scholarly journals Preferred screening test for Cushing’s syndrome screening

2020 ◽  
Vol 4 (1) ◽  
pp. 01-05
Author(s):  
Ahmed Siddiqi
Keyword(s):  
False Positive ◽  
Screening Test ◽  
False Negative ◽  
True Positive ◽  
True Negative ◽  
Inhaled Steroids ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Hospital General

Background: In our practice 24 hours urine collection for free cortisol (24Hr UFC) and overnight dexamethasone suppression test (ONDST) are initial investigations to screen patients for hyper-cortisolism. I audited our practice to find our clinicians’ and patients’ choice of first screening investigation for hyper-cortisolism. Method & material: Electronic and paper medical records of patients who underwent 24Hr UFC and/or ONDST at our hospital over previous consecutive twenty four months were examined. 62 such patients were identified but 12 patients were excluded from analysis. We tried to contact 30 patients over consecutive 48 hours over the phone who underwent both 24Hr UFC and ONDST. We managed to contact 18 patients and asked them two study questions. Data & results: 33 (66%) patients were female and 17 (33%) were male. 20 (40%) had 24Hr UFC alone and 30 (60%) patients had both. In total 80 such investigations completed 30 being ONDST and 50 24hr UFC. 53 (66%) of the investigations were requested by Endocrinologists, 21 (26%) by Hospital General Physicians and 6 (8%) by General practitioners (GP). For UFC 10 (20%) were true positive, 31 (62%) were false positive, 6 (12%) were true negative and 0% false negative. 3 (6%) 24Hr UFC samples were not collected properly and were not processed for results. Out of the total false positives (31 patients), 6 (19.3%) cases were of alcohol excess, 4 (13%) of dépression, 3 (9.7%) of inhaled steroids and 1 (3.2%) of sleep apnea. For the ONDST 7 (23.3%) true positive, 4 (13.3%) false positive 19 (63.4%) true negative and 0% false negative. All 18 patients contacted over the phone answered both questions. 16 preferred ONDST over 24Hr UFC, 1 patient had no preference and 1 patient preferred 24Hr UFC over ONDST. Conclusion: Patients overwhelmingly preferred ONDST as first screening test in contrast to physician’s choice of 24Hr UFC.

Urinary free cortisol and response to the dexamethasone suppression test in bulimia: A pilot study

1987 ◽  
Vol 6 (2) ◽  
pp. 191-198 ◽  
Author(s):  
James I. Hudson ◽  
David L. Katz ◽  
Harrison G. Pope ◽  
Margo S. Hudson ◽  
George T. Griffing ◽  
...  
Keyword(s):  
Pilot Study ◽  
Urinary Free Cortisol ◽  
Dexamethasone Suppression Test ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

scholarly journals Diagnostic value of salivary cortisol in 1-mg dexamethasone suppression test

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 ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Salivary Cortisol ◽  
Serum Cortisol ◽  
Dexamethasone Suppression Test ◽  
Histological Evaluation ◽  
Diagnostic Study ◽  
Late Night ◽  
Late Night Salivary Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

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.

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