scholarly journals Late-night and low-dose dexamethasone-suppressed cortisol in saliva and serum for the diagnosis of cortisol-secreting adrenal adenomas

2009 ◽  
Vol 161 (5) ◽  
pp. 747-753 ◽  
Author(s):  
Timo Deutschbein ◽  
Nicole Unger ◽  
Jakob Hinrichs ◽  
Martin K Walz ◽  
Klaus Mann ◽  
...  
Keyword(s):  
Low Dose ◽  
Serum Cortisol ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Operating Characteristics ◽  
Late Night ◽  
Free Cortisol ◽  
Characteristics Analysis ◽  
Receiver Operating Characteristics Analysis ◽  
Dexamethasone Suppression

ObjectiveIn patients with adrenal incidentalomas, hormonally active masses need to be considered, particularly cortisol-producing adenomas (CPA), aldosterone-producing adenomas, and pheochromocytomas. The screening for hypercortisolism relies on confirming excess cortisol secretion and insufficient suppression after dexamethasone. Because of its high correlation with free cortisol and its stress-free collection, salivary cortisol (SaC) may offer advantages over serum cortisol (SeC). We evaluated the value of SaC and SeC for the diagnosis of CPA.DesignComparative study between 2001 and 2006.MethodsThirty-eight patients with confirmed CPA were compared with 18 healthy subjects as well as 48 control patients suffering from aldosterone-producing adenomas (n=13), pheochromocytomas (n=16), or nonfunctioning adenomas (n=19). Sampling of saliva and serum was performed at 2300 and at 0800 h following low-dose dexamethasone suppression. Receiver operating characteristics analysis was used to calculate thresholds with at least 95% sensitivity for CPA.ResultsRegarding the cutoffs for late-night cortisol, SaC (4.8 nmol/l, sensitivity 97%, specificity 69%) was slightly more specific than SeC (115 nmol/l, sensitivity 97%, specificity 63%). In contrast, the cutoff for dexamethasone-suppressed SaC (3.7 nmol/l, sensitivity 97%, specificity 83%) was slightly less specific than SeC (94 nmol/l, sensitivity 97%, specificity 88%). However, the latter cutoffs demonstrated greater specificity when compared with the cutoffs for late-night cortisol.ConclusionThe diagnostic accuracy of SaC is as good as SeC. Owing to its higher specificity, dexamethasone-suppressed cortisol is preferable to late-night cortisol when screening for Cushing's syndrome in patients with adrenal incidentalomas.

scholarly journals Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas

2020 ◽  
Vol 9 (10) ◽  
pp. 963-970
Author(s):  
Grethe Å Ueland ◽  
Thea Grinde ◽  
Paal Methlie ◽  
Oskar Kelp ◽  
Kristian Løvås ◽  
...  
Keyword(s):  
False Negative ◽  
High Rate ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Late Night ◽  
Urine Free Cortisol ◽  
Saliva Cortisol ◽  
Free Cortisol ◽  
Autonomous Cortisol Secretion ◽  
Dexamethasone Suppression

Objective: Autonomous cortisol secretion (ACS) is a condition with ACTH-independent cortisol overproduction from adrenal incidentalomas (AI) or adrenal hyperplasia. The hypercortisolism is often mild, and most patients lack typical clinical features of overt Cushing’s syndrome (CS). ACS is not well defined and diagnostic tests lack validation. Methods: Retrospective study of 165 patients with AI evaluated clinically and by assay of morning plasma ACTH, late-night saliva cortisol, serum DHEA sulphate (DHEAS), 24-h urine-free cortisol, and cortisol after dexamethasone suppression. Results: Patients with AI (n = 165) were diagnosed as non-functioning incidentalomas (NFI) (n = 82) or ACS (n = 83) according to current European guidelines. Late-night saliva cortisol discriminated poorly between NFI and ACS, showing a high rate of false-positive (23/63) and false-negative (38/69) results. The conventional low-dose dexamethasone suppression test (LDDST) did not improve the diagnostic specificity, compared with the 1 mg overnight DST. Receiver operating characteristic curve analysis of DHEAS in the two cohorts demonstrated an area under the curve of 0.76 (P < 0.01) with a sensitivity for ACS of 58% and a specificity of 80% using the recommended cutoff at 1.04 µmol/L (40 µg/dL). Conclusion: We here demonstrate in a large retrospective cohort of incidentaloma patients, that neither DHEAS, late-night saliva cortisol nor 24-h urine free cortisol are useful to discriminate between non-functioning adrenal incidentalomas and ACS. The conventional LDDST do not add further information compared with the 1 mg overnight DST. Alternative biomarkers are needed to improve the diagnostic workup of ACS.

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 Bilateral and unilateral adrenal incidentalomas: biochemical and clinical characteristics

2013 ◽  
Vol 168 (2) ◽  
pp. 235-241 ◽  
Author(s):  
V Morelli ◽  
S Palmieri ◽  
A S Salcuni ◽  
C Eller-Vainicher ◽  
E Cairoli ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Adrenal Incidentalomas ◽  
Mineral Density ◽  
Femoral Bone Mineral Density ◽  
Free Cortisol ◽  
Suppression Test ◽  
Cortisol Levels ◽  
Dexamethasone Suppression

ObjectiveThe possible different prevalence of arterial hypertension (AH), type 2 diabetes mellitus (T2DM), dyslipidaemia (DL) and vertebral fractures (FX) between patients with bilateral and unilateral adrenal incidentalomas (BAI and UAI, respectively) with and without subclinical hypercortisolism (SH) is unknown. In this study we compared the prevalence of AH, T2DM, DL and FX in BAI and UAI patients in relation to SH.DesignProspective study.MethodsIn 175 UAI and 38 BAI patients, we evaluated BMI, spinal and femoral bone mineral density (LS and FN BMD, respectively) and the presence of AH, T2DM, DL and FX. SH was diagnosed in the presence of ≥2 of the following: urinary free cortisol levels >193 nmol/24 h, serum cortisol levels after 1 mg dexamethasone suppression test >83 nmol/l or ACTH levels <2.2 pmol/l.ResultsAge, BMI and cortisol secretion were comparable, while FN BMD was lower in BAI than in UAI patients (−0.45±0.86 vs 0.09±1.07, P=0.004). The prevalence of SH, AH, T2DM, and DL was comparable, while the prevalence of FX was higher in BAI than in UAI (52.6 vs 28%, P=0.007). The presence of FX was associated with BAI (odds ratio (OR) 2.6, 95% confidence interval (95% CI) 1.2–5.6, P=0.016), after adjusting for SH (OR 1.77, 95% CI 0.85–3.7, P=0.12), BMI (OR 1.06, 95% CI 0.98–1.13, P=0.1), age (OR 1.07, 95% CI 1.04–1.11, P=0.0001) and LS BMD (OR 1.31, 95% CI 1.03–1.67, P=0.03).ConclusionBAI patients have an increased FX risk than UAI ones. Further studies should investigate the causes of bone involvement in BAI patients.

scholarly journals Defining Nonfunctioning Adrenal Adenomas on the Basis of the Occurrence of Hypocortisolism after Adrenalectomy

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Cristina Eller-Vainicher ◽  
Valentina Morelli ◽  
Carmen Aresta ◽  
Antonio Stefano Salcuni ◽  
Alberto Falchetti ◽  
...  
Keyword(s):  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Tolerance Test ◽  
Cortisol Secretion ◽  
Unilateral Adrenalectomy ◽  
Insulin Tolerance ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression ◽  
Rule Out

Abstract Background In patients with adrenal incidentalomas (AIs), there is uncertainty on how to rule out hypercortisolism. The occurrence of postsurgical (unilateral adrenalectomy) hypocortisolism (PSH) has been proposed as a proof of the presence of presurgical hypercortisolism in AI patients. The aim of this study was to define the thresholds of cortisol level after the 1 mg overnight dexamethasone suppression test (F-1mgDST), urinary free cortisol (UFC), midnight serum cortisol (MSC), and adrenocorticotropin (ACTH) to predict the absence of PSH in AI patients undergoing surgery. Methods In 60 patients who underwent AI excision, cortisol secretion was assessed by a low-dose corticotropin stimulation test or insulin tolerance test when needed. We searched for the lowest presurgical value of F-1mgDST, UFC, and MSC and the highest value for ACTH in AI patients with PSH as indexes of normal cortisol secretion. Results The lowest values of F-1mgDST, UFC, and MSC and the highest value for ACTH in PSH patients were 1.2 µg/dL (33 nmol/L), 10.4 µg/24 hours (29 nmol/24 hours), 1.2 µg/dL (33 nmol/L), and 26.9 pg/mL (6 pmol/L), respectively, but only F-1mgDST &lt;1.2 µg/dL (33 nmol/L) was able to predict the absence of PSH. Among AI patients with F-1mgDST &lt;1.2 µg/dL (33 nmol/L) no subjects had diabetes mellitus and/or metabolic syndrome, and these subjects tended to have a better metabolic profile than those with F-1mgDST ≥1.2 µg/dL (33 nmol/L) Conclusion In AI patients a F-1mgDST &lt;1.2 µg/dL (33 nmol/L) rules out PSH and could be used to exclude hypercortisolism in AI patients.

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 Biochemical screening for subclinical cortisol-secreting adenomas amongst adrenal incidentalomas

2001 ◽  
pp. 401-408 ◽  
Author(s):  
N Valli ◽  
B Catargi ◽  
N Ronci ◽  
V Vergnot ◽  
F Leccia ◽  
...  
Keyword(s):  
Diurnal Variation ◽  
Screening Test ◽  
Serum Cortisol ◽  
Biochemical Parameter ◽  
Urinary Free Cortisol ◽  
Cortisol Concentration ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Free Cortisol ◽  
Biochemical Abnormalities

OBJECTIVE: Biochemistry and I-6beta-iodomethyl norcholesterol scintigraphy (IMS) have both been used to assess cortisol secretion by adrenocortical incidentalomas. However, which biochemical abnormalities indicate subclinical corticoid excess is still debatable whilst IMS is expensive and cumbersome. The aim of the study was to evaluate prospectively patients with adrenal incidentalomas using both IMS and biochemical methods to examine whether the IMS pattern is associated with biochemical abnormalities and, if this is so, to find a biochemical parameter that could be used as a screening test to identify a subset of patients on whom IMS could subsequently be performed. METHODS: Thirty-one patients with benign cortical adenomas were recruited from 43 consecutive patients with adrenal incidentalomas. All 31 patients underwent IMS and measurement of (i) 0800 h serum cortisol, ACTH, dehydroepiandrosterone and 17-hydroxyprogesterone; (ii) midnight serum cortisol; (iii) 2400 h excretion of urinary free cortisol; (iv) cortisol after the overnight 1 mg dexamethasone (DEX) suppression test; (v) cortisol after an i.v. 4 mg DEX test; (vi) determination of the diurnal variation in serum cortisol. RESULTS: Sixty-one per cent of patients displayed unilateral uptake during IMS and 39% showed bilateral uptake. Patients with unilateral uptake exhibited significantly lower ACTH concentrations (P=0.0005), higher midnight cortisol concentrations (P=0.02), disrupted diurnal variation of serum cortisol (P=0.02) and higher cortisol concentrations after DEX suppression tests (P=0.01). Cortisol concentrations following the two DEX suppression tests correlated closely (r=0.80, P=0.0001). The i.v. 4 mg DEX test was clearly more sensitive for the diagnosis of unilateral uptake than the overnight 1 mg DEX test (76 vs 52%). Using various thresholds of cortisol concentration following the overnight 1 mg DEX test, it was found that the sensitivity of the test could be improved to 100% if the threshold was set at 60 nmol/l rather than the classical value of 138 nmol/l. All patients but one with post-test serum cortisol concentrations above 60 nmol/l as against none of patients with cortisol below 60 nmol/l exhibited at least one associated biochemical abnormality indicating subclinical glucocorticoid excess. CONCLUSION: In adrenocortical incidentalomas, unilateral uptake during IMS suggests subclinically excessive and/or autonomous cortisol secretion. A cortisol concentration above 60 nmol/l following the overnight 1 mg DEX test is highly correlated with unilateral uptake and is associated with biochemical abnormalities indicating subclinical glucocorticoid excess. Our results favour the use of the 1 mg overnight DEX test with revised criteria of interpretation as a screening test for subclinical hypercortisolism among patients with adrenocortical incidentalomas.

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 (&lt; 13 nmol, n: &lt; 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.

scholarly journals Patients With Apparently Nonfunctioning Adrenal Incidentalomas May Be at Increased Cardiovascular Risk Due to Excessive Cortisol Secretion

2014 ◽  
Vol 99 (8) ◽  
pp. 2754-2762 ◽  
Author(s):  
Ioannis I. Androulakis ◽  
Gregory A. Kaltsas ◽  
Georgios E. Kollias ◽  
Athina C. Markou ◽  
Aggeliki K. Gouli ◽  
...  
Keyword(s):  
Low Dose ◽  
Area Under The Curve ◽  
Urinary Free Cortisol ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Acth Stimulation ◽  
Adrenal Imaging ◽  
Free Cortisol ◽  
Suppression Test ◽  
Dexamethasone Suppression

Context: Although adrenal incidentalomas (AIs) are associated with a high prevalence of cardiovascular risk (CVR) factors, it is not clear whether patients with nonfunctioning AI (NFAI) have increased CVR. Objective: Our objective was to investigate CVR in patients with NFAI. Design and Setting: This case-control study was performed in a tertiary general hospital. Subjects: Subjects included 60 normotensive euglycemic patients with AI and 32 healthy controls (C) with normal adrenal imaging. Main Outcome Measures: All participants underwent adrenal imaging, biochemical and hormonal evaluation, and the following investigations: 1) measurement of carotid intima-media thickness (IMT) and flow-mediated dilatation, 2) 2-hour 75-gram oral glucose tolerance test and calculation of insulin resistance indices (homeostasis model assessment, quantitative insulin sensitivity check, and Matsuda indices), 3) iv ACTH stimulation test, 4) low-dose dexamethasone suppression test, and 5) NaCl (0.9%) post-dexamethasone saline infusion test. Results: Based on cutoffs obtained from controls, autonomous cortisol secretion was documented in 26 patients (cortisol-secreting AI [CSAI] group), whereas 34 exhibited adequate cortisol and aldosterone suppression (NFAI group). IMT measurements were higher and flow-mediated vasodilatation was lower in the CSAI group compared with both NFAI and C and in the NFAI group compared with C. The homeostasis model assessment index was higher and quantitative insulin sensitivity check index and Matsuda indices were lower in the CSAI and NFAI groups compared with C as well as in CSAI compared with the NFAI group. The area under the curve for cortisol after ACTH stimulation was higher in the CSAI group compared with the NFAI group and C and in the NFAI group compared with C. In the CSAI group, IMT correlated with cortisol, urinary free cortisol, and cortisol after a low-dose dexamethasone suppression test, whereas in the NFAI group, IMT correlated with area under the curve for cortisol after ACTH stimulation and urinary free cortisol. Conclusions: Patients with CSAI without hypertension, diabetes, and/or dyslipidemia exhibit adverse metabolic and CVR factors. In addition, NFAIs are apparently associated with increased insulin resistance and endothelial dysfunction that correlate with subtle but not autonomous cortisol excess.

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