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

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.

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 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 < 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 <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 <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.

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.

scholarly journals SAT-LB46 Depression as an Atypical Presentation of Cushing’s Disease

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dhivya Pahwa ◽  
Michael Howard Shanik
Keyword(s):  
Cushing’S Disease ◽  
Psychiatric Symptoms ◽  
Venous Blood ◽  
Dexamethasone Suppression Test ◽  
Cushing's Disease ◽  
Endocrine Society ◽  
Free Cortisol ◽  
Suppression Test ◽  
The Right ◽  
Dexamethasone Suppression

Abstract Introduction: Cushing’s disease is an abnormal secretion of ACTH from the pituitary that causes an increase in cortisol production from the adrenal glands. Resultant manifestations from this excess in cortisol include multiple metabolic as well as psychiatric disturbances which can lead to significant morbidity and mortality. Case: The patient is a 29 year old woman who presented with fatigue, decreased energy, poor memory and insomnia for 3 months. She noted irregular menses for 4 months. She was referred from her primary doctor for elevated salivary cortisol and DHEA levels. Evaluation revealed BP: 104/76, HR 78, RR 12, BMI 22.7. She was a thin woman without striae, moon face, buffalo hump or bruising. 24 hour urine free cortisol was 90.3 mcg/24hr. One mg dexamethasone suppression test resulted in an AM cortisol of 17.6 ug/dL and ACTH 25 pg/mL. An 8 mg dexamethasone suppression test showed a cortisol level of 1.2 ug/dL with an ACTH <5 pg/mL. The combined results were suggestive of Cushing’s disease. The patient went for MRI of the pituitary which showed a 4 mm hypoenhancing region on the right side of the gland suspicious for a microadenoma. The patient was followed closely and continued to report fatigue and insomnia. Inferior petrosal sinus sampling was performed. Venous blood sampling of ACTH from the periphery at 0 min, 5 min and 15 min were: <5 pg/mL, <5 pg/mL, and <5 pg/mL respectively. On the right at 0 min, 1 min, 5 min, 15 min ACTH levels were: 12 pg/mL, 14 pg/mL, 16 pg/mL, 14 pg/mL. On the left at 5 min and 15 min ACTH measured 8 pg/mL and 7 pg/mL. These findings confirmed the suspicion of a right-sided ACTH-secreting pituitary adenoma. She was referred to a neurosurgeon to evaluate for resection of the adenoma. Due to the ongoing symptoms, the neurosurgical removal of the lesion was expedited and scheduled within several weeks. While awaiting removal the patient sadly took her own life. Conclusion: Aside from the more commonly associated metabolic manifestations of elevated cortisol levels, psychiatric symptoms can be the initial complaint of patients with Cushing’s disease. Symptoms can include fatigue, depressive symptoms, insomnia, and sleep dysregulation. Currently the Endocrine Society Guideline for Cushing’s syndrome does not have any specific recommendations regarding depression screening. Psychiatric complications are a known manifestation of Cushing’s disease. Close follow up and urgent psychiatric referral with the onset of signs of depression or anxiety should be included as part of Cushing’s disease evaluation. Symptoms of mental health disturbances may be subtle and thus all patients with Cushing’s disease should be screened and monitored for underlying psychiatric illnesses. Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5152600/pdf/JMedLife-09-12.pdf

scholarly journals Diagnostic tests for Cushing's syndrome differ from published guidelines: data from ERCUSYN

2017 ◽  
Vol 176 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Elena Valassi ◽  
Holger Franz ◽  
Thierry Brue ◽  
Richard A Feelders ◽  
Romana Netea-Maier ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Diagnostic Tests ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Dexamethasone Suppression Test ◽  
Diagnostic Tools ◽  
Late Night ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

Objective To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing’s syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods We analyzed data on the diagnostic tests performed in 1341 patients with Cushing’s syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). Conclusions Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.

scholarly journals Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A86-A87
Author(s):  
Karthik Subbu ◽  
Zunera Tariq ◽  
Dana Z Erickson ◽  
Irina Bancos ◽  
Diane Donegan
Keyword(s):  
Cushing Syndrome ◽  
Dexamethasone Suppression Test ◽  
Thromboembolic Events ◽  
Increased Risk ◽  
Free Cortisol ◽  
Venous Thromboembolic Events ◽  
Venous Thromboembolic ◽  
Suppression Test ◽  
Clinically Significant ◽  
Dexamethasone Suppression

Abstract Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred &gt;3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P &lt; 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.

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