SAT-376 Dynamic Modeling of the 1 mg Overnight Dexamethasone Suppression Test: Sources of Variability and Strategies to Improve Diagnostic Accuracy for Detection of Autonomous Cortisol Secretion in Adrenal Adenoma Patients

Akshaya Kambhatla; Clifford Qualls; Frank Urban; Richard Dorin

doi:10.1210/js.2019-sat-376

Accuracy of the dexamethasone suppression test for the prediction of autonomous cortisol secretion-related comorbidities in adrenal incidentalomas

HORMONES ◽

10.1007/s42000-021-00308-z ◽

2021 ◽

Author(s):

Marta Araujo-Castro ◽

Paola Parra Ramírez ◽

Cristina Robles Lázaro ◽

Rogelio García Centeno ◽

Paola Gracia Gimeno ◽

...

Keyword(s):

Dexamethasone Suppression Test ◽

Cortisol Secretion ◽

Adrenal Incidentalomas ◽

Suppression Test ◽

Autonomous Cortisol Secretion ◽

Dexamethasone Suppression

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THE QUANTITATIVE RELATIONSHIP BETWEEN AUTONOMOUS CORTISOL SECRETION, DYSGLYCEMIA AND THE METABOLIC SYNDROME

Endocrine Practice ◽

10.4158/ep-2020-0111 ◽

2020 ◽

Vol 26 (9) ◽

pp. 974-982

Author(s):

Jonathan Bleier ◽

Gadi Shlomai ◽

Boris Fishman ◽

Zohar Dotan ◽

Barak Rosenzweig ◽

...

Keyword(s):

Metabolic Syndrome ◽

Plasma Glucose ◽

Hemoglobin A1c ◽

Dexamethasone Suppression Test ◽

Cortisol Secretion ◽

Adrenal Incidentalomas ◽

Continuous Parameter ◽

Suppression Test ◽

Autonomous Cortisol Secretion ◽

Dexamethasone Suppression

Objective: Autonomous cortisol secretion (ACS) is the most common endocrine abnormality in the evaluation of adrenal incidentalomas. The categorization of ACS is derived from a 1 mg dexamethasone suppression test (DST). Impaired DST is associated with several metabolic derangements. In this study we analyzed the association between post-DST cortisol level, analyzed as a continuous parameter, and indices of glycemic metabolism. Methods: We prospectively collected data of 1,976 patients evaluated for adrenal incidentalomas in a large tertiary medical center between December 1, 2017, and August 31, 2019. Seventy-three patients completed the evaluation process. Post-DST cortisol levels were analyzed for correlation with various metabolic parameters, including fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) among the general cohort and for subgroups stratified by the number of metabolic syndrome (MS) criteria. Results: Post-DST cortisol demonstrated a linear association with FPG and HbA1c across its entire cortisol range ( R = 0.51 and 0.41, respectively; P≤.01). The association between post-DST cortisol and FPG was strengthened with an increased number of metabolic syndrome criteria. Patients with 4 MS criteria show a stronger association ( R = 0.92) compared to patients with only a single criterion ( R = 0.509). Furthermore, mean post-DST cortisol levels increased as the number of MS criteria accumulated. Conclusion: Post-DST cortisol should be viewed as a continuous parameter in risk stratification algorithms for the development of MS and particularly dysglycemia. Abbreviations: ACS = autonomous cortisol secretion; AI = adrenal incidentaloma; BMI = body mass index; BP = blood pressure; DM = diabetes mellitus; DST = dexamethasone suppression test; FPG = fasting plasma glucose; HbA1c = hemoglobin A1c; HDL = high-density lipoprotein; MS = metabolic syndrome; TG = triglycerides; WHR = waist-to-hip ratio

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

Endocrine Practice ◽

10.1016/s1530-891x(20)46474-2 ◽

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

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Biochemically silent phaeochromocytoma presenting with non-specific loin pain

BMJ Case Reports ◽

10.1136/bcr-2021-244258 ◽

2021 ◽

Vol 14 (8) ◽

pp. e244258

Author(s):

Annalisa Montebello ◽

Etienne Ceci Bonello ◽

Miriam Giordano Imbroll ◽

Mark Gruppetta

Keyword(s):

Adrenal Adenoma ◽

Dexamethasone Suppression Test ◽

Adrenal Lesion ◽

Genetic Mutations ◽

Large Size ◽

History Of ◽

Loin Pain ◽

Suppression Test ◽

Aldosterone To Renin Ratio ◽

Dexamethasone Suppression

A 55-year-old woman presented with a 4-month history of right-sided non-specific loin pain and 6 kg weight loss. A CT scan of the abdomen and pelvis showed an incidental 4.5 cm right-sided adrenal lesion which was not typical of an adrenal adenoma. This was further confirmed on MRI of the adrenals. Biochemical investigations to investigate for a functional adrenal lesion included serum catecholamines and metanephrines, an aldosterone to renin ratio and an overnight dexamethasone suppression test. These were all negative. A laparoscopic adrenalectomy was performed in view of the large size of the lesion. Histology was consistent with a phaeochromocytoma, which confirmed the diagnosis of a non-secreting phaeochromocytoma. Non-secreting phaeochromocytomas are rare and usually found in patients with known genetic mutations. Adrenal lesions not related to any mutations similar to our case are even rarer and reported even less in the literature.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab724 ◽

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.

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Suppression of cortisol secretion by low-dose dexamethasone testing in Cushing's disease

Journal of Neurosurgery ◽

10.3171/jns.1983.58.1.0129 ◽

1983 ◽

Vol 58 (1) ◽

pp. 129-132 ◽

Cited By ~ 1

Author(s):

Lucille W. King ◽

Kalmon D. Post ◽

Israel Yust ◽

Seymour Reichlin

Keyword(s):

Cushing’S Disease ◽

Low Dose ◽

Dexamethasone Suppression Test ◽

Cushing's Disease ◽

Cortisol Secretion ◽

Content Type ◽

Normal Individuals ◽

Suppression Test ◽

Peripheral Clearance ◽

Dexamethasone Suppression

✓ Pituitary-adrenal function in a patient with classical features of Cushing's disease, increased urinary excretion of cortisol, and documented pituitary adenoma was found to be suppressed by dexamethasone in doses even less than those required to inhibit secretion in normal individuals. This response was shown to be due to inappropriately high levels of dexamethasone in plasma, presumed to be the consequence of decreased peripheral clearance. Because the dexamethasone suppression test is so widely used for diagnosis of Cushing's disease, it is important to recognize that this situation can occasionally occur.

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Simultaneous assay of cortisol and dexamethasone improved diagnostic accuracy of the dexamethasone suppression test

Acta Endocrinologica ◽

10.1530/eje-17-0078 ◽

2017 ◽

Vol 176 (6) ◽

pp. 705-713 ◽

Cited By ~ 19

Author(s):

Grethe Å Ueland ◽

Paal Methlie ◽

Ralf Kellmann ◽

Marit Bjørgaas ◽

Bjørn O Åsvold ◽

...

Keyword(s):

Simultaneous Measurement ◽

High Sensitivity ◽

Cortisol Secretion ◽

Replication Cohort ◽

Non Invasive ◽

Liquid Chromatography Tandem Mass ◽

Suppression Test ◽

Autonomous Cortisol Secretion ◽

Design And Methods ◽

Dexamethasone Suppression

ObjectivesThe overnight dexamethasone (DXM) suppression test (DST) has high sensitivity, but moderate specificity, for diagnosing hypercortisolism. We have evaluated if simultaneous measurement of S-DXM may correct for variable DXM bioavailability and increase the diagnostic performance of DST, and if saliva (sa) is a feasible adjunct or alternative to serum.Design and methodsProspective study of DST was carried out in patients with suspected Cushing’s syndrome (CS) (n = 49), incidentaloma (n = 152) and healthy controls (n = 101). Cortisol, cortisone and DXM were assayed by liquid chromatography–tandem mass spectrometry (LC–MS/MS).ResultsThree hundred and two subjects underwent DST; S-cortisol was ≥50 nmol/L in 83 patients, of whom 11 had CS and 27 had autonomous cortisol secretion. The lower 2.5 percentile of S-DXM in subjects with negative DST (n = 208) was 3.3 nmol/L, which was selected as the DXM cut-off level. Nine patients had the combination of low S-DXM and positive DST. Of these, three had been misdiagnosed as having autonomous cortisol secretion. DST results were highly reproducible and confirmed in a replication cohort (n = 58). Patients with overt CS had significantly elevated post-DST sa-cortisol and sa-cortisone levels compared with controls; 23 of 25 with autonomous cortisol secretion had elevated sa-cortisone and 14 had elevated sa-cortisol.ConclusionsSimultaneous measurement of serum DXM and cortisol reduced false-positive DSTs by 20% and improved the specificity. S-DXM >3.3 nmol/L is sufficient for the suppression of cortisol <50 nmol/L. Measurement of glucocorticoids in saliva is a non-invasive and easy procedure and post-DST sa-cortisone was found particularly useful in the diagnosis of CS.

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

Obesity and metabolism ◽

10.14341/omet10117 ◽

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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MON-222 Cardiovascular Risk Factors, Morbidity, and Overall Mortality in Patients with Adrenal Adenomas: A Population-Based Study of 1,003 Patients

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.954 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Catherine D Zhang ◽

Elizabeth J Atkinson ◽

Sara J Achenbach ◽

Andreas Ladefoged Ebbehøj ◽

Dingfeng Li ◽

...

Keyword(s):

Risk Factors ◽

Cardiovascular Events ◽

Population Based ◽

Dexamethasone Suppression Test ◽

Adrenal Tumors ◽

Cortisol Secretion ◽

Peripheral Vascular ◽

Suppression Test ◽

Dexamethasone Suppression ◽

Age And Sex

Abstract Background: Benign adrenal tumors are frequently diagnosed on imaging and may pose health risks to patients regardless of functional status. Both non-functioning adrenal tumors (NFAT) and tumors with mild autonomous cortisol secretion (MACS) have been associated with increased cardiovascular events and risk factors. However, limited data exist on the association of adrenal adenomas with cardiometabolic outcomes in the population-based setting. Aim: 1) To determine the prevalence of cardiovascular co-morbidities and events and 2) to assess mortality in a population-based cohort of patients with adrenal adenomas. Methods: We identified adult patients living in the community diagnosed with an adrenal tumor from 1995-2017 using a medical records linkage system. Adrenal tumors were classified as MACS if cortisol was ≥1.8mcg/dL after 1 mg dexamethasone suppression test, NFAT if cortisol was <1.8 mcg/dL, and adenoma with unknown cortisol secretion (AUCS) if dexamethasone suppression test was not performed. Cardiovascular co-morbidities and events were assessed at baseline. Patients were then followed until death, migration out of the community, or through December 31, 2018. Results were compared to age and sex matched reference subjects without adrenal tumors and adjusted for tobacco use and BMI. Results: A total of 1,003 patients had adrenal adenomas with 136 (14%) NFAT, 86 (9%) MACS, and 781 (78%) AUCS. The median age of diagnosis was 63 years (range, 20-96) and 581 (58%) were women. At baseline, patients with adrenal adenomas were more likely to have hypertension (92% vs 81%, p<0.001), overweight/obesity (89% vs 82%, p<0.001), pre-diabetes/diabetes (82% vs 70%, p<0.001), dyslipidemia (89% vs 82%, p<0.001), and chronic kidney disease (11% vs 7%, p=0.004) than age and sex matched reference subjects. Myocardial infarctions (13% vs 8%, p <0.001), coronary intervention (9% vs 6%, p= 0.007), heart failure (12% vs 6%, p<0.001), peripheral vascular disease (26% vs 15%, p<0.001), and thromboembolic disease (7% vs 3%, p<0.001) were more prevalent in patients with adrenal adenomas, whereas overall survival was lower compared to reference subjects (60% vs 65%, p value = 0.013). Subgroup analysis (adjusted for age, sex, BMI, and smoking) demonstrated prevalence of cardiovascular events including peripheral vascular disease was highest in those with MACS (44.7%), followed by AUCS (40.1%), and then NFAT (36.6%), although differences between groups were not significant. Overall survival was lower in patients with MACS (62%) and AUCS (59%) compared to NFAT (71%), p<0.001. Conclusions: Adrenal adenomas are associated with significantly higher prevalence of cardiovascular risk factors and morbidity at the time of diagnosis and with increased morality during follow-up. Results are potentially related to abnormal cortisol secretion but are limited by suboptimal evaluation for hormone excess.

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Co-Occurrence of Exogenous and Endogenous Cushing’s Syndromes—Dilemma in Diagnosis

Case Reports in Endocrinology ◽

10.1155/2019/2986312 ◽

2019 ◽

Vol 2019 ◽

pp. 1-3

Author(s):

Chin Voon Tong ◽

Subashini Rajoo

Keyword(s):

Cushing’S Syndrome ◽

Adrenal Adenoma ◽

Cushing's Syndrome ◽

Dexamethasone Suppression Test ◽

Adrenal Cortical Adenoma ◽

Thin Skin ◽

History Of ◽

Musculoskeletal Manifestations ◽

Suppression Test ◽

Dexamethasone Suppression

Approach to patients who manifest with features of Cushing’s syndrome often begin with exclusion of exposure to excessive exogenous source of glucocorticoids (GC). Most guidelines advocate no further assessment if excessive exogenous GC use is present. We present a case of a 66-year-old lady who was noted to have typical features of Cushing’s syndrome. As she gave a very clear history of ingesting exogenous GC for a year, no further work up was undertaken. Despite cessation of GC for a year, she continued to have thin skin and easy bruising. Upon admission for hypertensive emergency, her clinician took note of her changes and investigated her for endogenous Cushing’s syndrome. Her cortisol post overnight dexamethasone suppression test was 707 nmol/l. Post low dose dexamethasone suppression test yielded a cortisol of 1133.2 nmol/l. 24 hours urine cortisol was 432.2 nmol/l. Plasma ACTH was 1.1 pmol/l, indicating an ACTH independent Cushing’s syndrome. We proceeded with Computed tomography scan (CT scan) of adrenals which revealed a right adrenal adenoma measuring 4.4 × 3.4 × 4.0 cm. Right retroperiteneoscopic adrenalectomy was done. Histopathology examination was consistent with adrenal cortical adenoma with foci of myelolipoma. Post adrenalectomy she developed hypocortisolism secondary to contralateral adrenal suppression which lasted up to the present date. Her cutaneous and musculoskeletal manifestations improved substantially. Co-occurrence of endogenous and exogenous Cushing’s syndromes is uncommon but should be considered in patients whose Cushingnoid features do not resolve after cessation of exogenous GC.

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