Enhanced performance of a modified diagnostic test of primary aldosteronism in patients with adrenal adenomas

2021 ◽  
Author(s):  
Athina Markou ◽  
Gregory A Kaltsas ◽  
Labrini Papanastasiou ◽  
Chris Gravvanis ◽  
Nick Voulgaris ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Adrenal Adenoma ◽  
Plasma Renin ◽  
Serum Cortisol ◽  
Cortisol Secretion ◽  
Normal Limits ◽  
Adrenal Imaging ◽  
Increased Risk ◽  
Autonomous Cortisol Secretion ◽  
Aldosterone To Renin Ratio

Objective: Primary aldosteronism (PA) is the commonest cause of endocrine hypertension ranging from 4.6%-16.6% according to the diagnostic tests employed. The aim of this study was to compare the traditional saline infusion test (SIT) with the modified post-dexamethasone SIT (DSIT) by applying both tests on the same subjects. Methods: We studied 68 patients (72% hypertensives) with single adrenal adenoma and 55 normotensive controls, with normal adrenal imaging. Serum cortisol, aldosterone and plasma renin concentration (PRC) were measured and the aldosterone-to-renin ratio (ARR) was calculated. Using the mean+2SD values from the controls, we defined the upper normal limits (UNL) for cortisol, aldosterone and PRC for both the SIT and DSIT. Results: In the controls, the post-DSIT aldosterone levels and the ARR were approximately 2-fold and 3-fold lower respectively than the corresponding post-SIT values (all p=0.001) leading to lower cut-offs of aldosterone suppression. Applying these cut-offs to patients with adrenal adenomas, the prevalence of PA was 13.2% following the SIT and 29.4% following the DSIT, respectively. In addition, 54.5% of patients with PA had concomitant autonomous cortisol secretion. Targeted treatment of PA resulted in resolution of hypertension and restoration of normal secretory aldosterone dynamics. Conclusions: The DSIT improves the diagnostic accuracy of PA, allowing for the detection of milder forms of PA in patients with adrenal adenomas. This is of particular importance as such patients may be at an increased risk for developing cardiovascular and renal morbidity that could be enhanced in the presence of concomitant autonomous cortisol secretion.

scholarly journals Mild Autonomous Cortisol Secretion in Primary Aldosteronism Enhances Renal and Hemorrhagic Cerebrovascular Complications

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A294-A294
Author(s):  
Ren Matsuba ◽  
Takuyuki Katabami ◽  
Isao Kurihara ◽  
Takamasa Ichijo ◽  
Yoshiyu Takeda ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Cerebral Hemorrhage ◽  
Adrenal Tumor ◽  
Serum Cortisol ◽  
Tumor Diameter ◽  
Cortisol Secretion ◽  
Acth Stimulation ◽  
Plasma Aldosterone Concentration ◽  
Cerebrovascular Complications ◽  
Autonomous Cortisol Secretion

Abstract Background: It is well known that primary aldosteronism (PA) is often associated with renal dysfunction and cardiovascular events (CVEs). However, the synergic effect of mild autonomous cortisol secretion (MACS) on the co-morbidities among PA has not been clarified yet. Thus, we retrospectively assessed whether the presence of MACS in PA patients with adrenal tumor, which may have MACS, to enhance the risk of the complications using a large Japanese multicenter database. Methods: We enrolled patients with both confirmed PA and obvious adrenal tumor (diameter > 1 cm) on computed tomography. The subtype of PA was diagnosed based on the results of adrenal venous sampling with ACTH stimulation. A total of 575 study subjects were stratified into two groups according to 1-mg dexamethasone suppression test (DST) results (cut-off post-DST serum cortisol 1.8 µg/dL): MACS group (N=174, 30.2%) and non-MACS group (N=401, 69.8%). Decreased estimated glomerular filtration rate (eGFR) was defined as <60 ml/min per 1.73m2. Results: The percentage of unilateral PA between the MACS and non-MACS group was equivalent (50.0% vs. 48.1%). Prevalence of decreased eGFR in the MACS group was higher than in the non-MACS group [odds ratio (OR) 1.91, 95% confidence interval (95% CI) 1.20–3.04, P=0.006]. Conversely, prevalence of MACS was higher in patients with decreased eGFR than those without decreased eGFR (42.7% vs 28.0%, P=0.008). Proteinuria was deteriorated with the increase in post-DST serum cortisol concentration as well as the basal plasma aldosterone concentration (PAC) (P=0.028 and P<0.001, respectively), although PAC but not the presence of MACS was selected as an independent factor related with decreased eGFR. Prevalence of cerebral hemorrhage in the MACS group was higher than the non-MACS group. (OR 5.35, 95%CI 1.83–15.6, P=0.002). We found that MACS was the only significant factor which increased the odds of developing cerebral hemorrhage (OR 9.13, 95%CI 2.15–38.90, P=0.003). Prevalence of other CVEs between the two groups was similar. Regardless of the PA subtype, complication rate of decreased eGFR and cerebral bleeding in the MACS group were significantly or tend to be higher than non-MACS group. Conclusion: Our date strongly suggested that co-secretion of cortisol in PA directly and/or indirectly increase renal and cerebrovascular comorbidities. Given that MACS is common in PA, endocrinological testing with DST is recommended in PA patients, especially those with adrenal tumor on imaging. (Supported by Research Grants of AMED:JP17ek0109122, JP20ek0109352; National Center for Global Health and Medicine:27–1402, 30–1008), and Ministry of Health, Labour, and Welfare, Japan (046).

scholarly journals Incident Cardiometabolic Outcomes in Adrenal Adenomas: A Population-Based Cohort Study of 1,004 Patients

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A87-A87
Author(s):  
Catherine D Zhang ◽  
Elizabeth J Atkinson ◽  
Sara J Achenbach ◽  
Andreas Ladefoged Ebbehøj ◽  
Dingfeng Li ◽  
...  
Keyword(s):  
Cohort Study ◽  
Adrenal Adenoma ◽  
Serum Cortisol ◽  
Coronary Intervention ◽  
Population Based ◽  
Medical Community ◽  
Cortisol Secretion ◽  
Age Of Diagnosis ◽  
Suppression Test ◽  
Autonomous Cortisol Secretion

Abstract Background: Adrenal adenomas have been linked with cardiovascular morbidity in selected patient populations from specialized referral centers. Population-based data examining the association of adrenal adenomas with cardiometabolic outcomes are lacking. Aim: To determine the incidence of cardiometabolic outcomes in a population-based cohort of patients with adrenal adenomas. Methods: We conducted a population-based cohort study of patients diagnosed with adrenal adenomas while living in a defined community from 1995–2017. Eligible patients were retrospectively identified by a medical records linkage system and confirmed on chart review. Adenomas were classified as mild autonomous cortisol secretion (MACS) if the serum cortisol concentration was >1.8 mcg/dL after 1 mg overnight dexamethasone suppression test (DST), nonfunctioning adrenal tumor (NFAT) if serum cortisol after DST was ≤1.8 mcg/dL, and adenoma with unknown cortisol secretion (AUCS) if DST was not performed. Patients with overt hormone excess were excluded. Cardiometabolic outcomes were assessed at the time of adrenal adenoma diagnosis. Patients were then followed until death, migration out of the community, or through December 31, 2017. Incident outcomes were assessed starting at 1 year following the diagnosis and excluded those with the outcome of interest at baseline, except for myocardial infarction (MI) and coronary intervention, which were adjusted for in the analysis. Results: were compared to 1:1 age and sex-matched referent subjects without adrenal adenomas from the same community. Results: Adrenal adenomas were diagnosed in 1004 patients with 141 (14%) NFAT, 81 (8%) MACS, and 782 (78%) AUCS. The median age of diagnosis was 63 years (range, 20–96), and 582 (58%) were women. The baseline data was previously presented and showed higher prevalence of hypertension, diabetes, peripheral vascular disease (PVD), and heart failure (HF) in the adenoma group, after adjusting for BMI and tobacco use. During a median follow-up of 6.8 years (range, 0–22), patients with adrenal adenomas were more likely than referent subjects to develop new-onset dyslipidemia (HR 1.31, 95% CI 1.03–1.67), diabetes (HR 1.68, 95% CI 1.28–2.22), chronic kidney disease (HR 1.77, 95% CI 1.39–2.25), atrial fibrillation (HR 1.32 (1.03–1.70), PVD (HR 1.61, 95% CI 1.24–2.09), and HF (HR 1.46, 95% CI 1.15–1.85). In addition, the adenoma group had higher risk for incident MI (HR 1.62, 95% CI 1.16–2.25) and coronary intervention (HR 1.70, 95% CI 1.25–2.31). Conclusions: Adrenal adenomas are associated with increased incidence of adverse cardiometabolic outcomes in this population-based cohort study. While these results are potentially explained by different degrees of cortisol excess, the majority of patients received suboptimal hormone evaluation, suggesting a knowledge gap in the workup of adrenal adenomas in the broader medical community.

scholarly journals Primary Aldosteronism Caused by a Unilateral Adrenal Adenoma Accompanied by Autonomous Cortisol Secretion

2007 ◽  
Vol 30 (4) ◽  
pp. 367-373 ◽  
Author(s):  
Jiro SUZUKI ◽  
Fumio OTSUKA ◽  
Kenichi INAGAKI ◽  
Hiroyuki OTANI ◽  
Tomoko MIYOSHI ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Adrenal Adenoma ◽  
Cortisol Secretion ◽  
Autonomous Cortisol Secretion

The association between adrenal adenoma size, autonomous cortisol secretion and metabolic derangements

2021 ◽  
Author(s):  
Jonathan Bleier ◽  
Jana Pickovsky ◽  
Sara Apter ◽  
Boris Fishman ◽  
Zohar Dotan ◽  
...  
Keyword(s):  
Adrenal Adenoma ◽  
Cortisol Secretion ◽  
Autonomous Cortisol Secretion

Prevalence of Primary Aldosteronism Across the Stages of Hypertension Based on a New Combined Overnight Test

2021 ◽  
Vol 53 (07) ◽  
pp. 461-469
Author(s):  
Nick Voulgaris ◽  
Ernestini Tyfoxylou ◽  
Sophia Vlachou ◽  
Evagelia Kyriazi ◽  
Chris Gravvanis ◽  
...  
Keyword(s):  
Arterial Hypertension ◽  
Primary Aldosteronism ◽  
Adrenocorticotropic Hormone ◽  
Stage I ◽  
Aldosterone Secretion ◽  
Hypertensive Patients ◽  
True Prevalence ◽  
Normal Limits ◽  
Aldosterone To Renin Ratio ◽  
A Prospective Study

AbstractPrimary aldosteronism (PA) is the most common endocrine cause of arterial hypertension. Despite the increasing incidence of hypertension worldwide, the true prevalence of PA in hypertension was only recently recognized. The objective of the work was to estimate the prevalence of PA in patients at different stages of hypertension based on a newly developed screening-diagnostic overnight test. This is a prospective study with hypertensive patients (n=265) at stage I (n=100), II (n=88), and III (n=77) of hypertension. A group of 103 patients with essential hypertension without PA was used as controls. PA diagnosis was based on a combined screening-diagnostic overnight test, the Dexamethasone-Captopril-Valsartan Test (DCVT) that evaluates aldosterone secretion after pharmaceutical blockade of angiotensin-II and adrenocorticotropic hormone. DCVT was performed in all participants independently of the basal aldosterone to renin ratio (ARR). The calculated upper normal limits for post-DCVT aldosterone levels [3 ng/dl (85 pmol/l)] and post-DCVT ARR [0.32 ng/dl/μU/ml (9 pmol/IU)] from controls, were applied together to establish PA diagnosis. Using these criteria PA was confirmed in 80 of 265 (30%) hypertensives. The prevalence of PA was: 21% (21/100) in stage I, 33% (29/88) in stage II, and 39% (30/77) in stage III. Serum K+ levels were negatively correlated and urinary K+ was positively correlated in PA patients with post-DCVT ARR (r=–0.349, p <0.01, and r=0.27, p <0.05 respectively). In conclusion, DCVT revealed that PA is a highly prevalent cause of hypertension. DCVT could be employed as a diagnostic tool in all subjects with arterial hypertension of unknown cause.

scholarly journals Cardiovascular Outcomes in Autonomous Cortisol Secretion and Nonfunctioning Adrenal Adenoma: A Systematic Review

2019 ◽  
Vol 3 (5) ◽  
pp. 996-1008 ◽  
Author(s):  
Jane Park ◽  
Alyssa De Luca ◽  
Heidi Dutton ◽  
Janine C Malcolm ◽  
Mary-Anne Doyle
Keyword(s):  
Systematic Review ◽  
Adrenal Adenoma ◽  
Cardiovascular Outcomes ◽  
Cortisol Secretion ◽  
Autonomous Cortisol Secretion

scholarly journals Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors

2016 ◽  
Vol 175 (2) ◽  
pp. G1-G34 ◽  
Author(s):  
Martin Fassnacht ◽  
Wiebke Arlt ◽  
Irina Bancos ◽  
Henning Dralle ◽  
John Newell-Price ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Adrenal Mass ◽  
Adrenal Incidentaloma ◽  
Serum Cortisol ◽  
Cushing's Syndrome ◽  
Cortisol Secretion ◽  
Adrenal Incidentalomas ◽  
Adrenal Masses ◽  
Autonomous Cortisol Secretion

By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called ‘subclinical’ Cushing’s syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed?Selected recommendations:(i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing’s syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term ‘autonomous cortisol secretion’. (iv) All patients with ‘(possible) autonomous cortisol’ secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with ‘autonomous cortisol secretion’ who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas

scholarly journals Dietary Sodium Restriction Increases the Risk of Misinterpreting Mild Cases of Primary Aldosteronism

2016 ◽  
Vol 101 (11) ◽  
pp. 3989-3996 ◽  
Author(s):  
Rene Baudrand ◽  
Francisco J. Guarda ◽  
Jasmine Torrey ◽  
Gordon Williams ◽  
Anand Vaidya
Keyword(s):  
Primary Aldosteronism ◽  
Sodium Intake ◽  
Plasma Renin ◽  
Dietary Sodium ◽  
Sodium Restriction ◽  
Positive Screen ◽  
Serum Aldosterone ◽  
Optimal Screening ◽  
Dietary Sodium Restriction ◽  
Aldosterone To Renin Ratio

Context: The aldosterone to renin ratio (ARR) is recommended to screen for primary aldosteronism (PA). Objective: To evaluate whether dietary sodium restriction results in misinterpretation of PA screening. Participants: Untreated hypertensives with ARR more than 20 on a high dietary sodium intake (HS) were also evaluated on a low dietary sodium intake (LS) (n = 241). Positive screening for PA was defined as: plasma renin activity (PRA) less than or equal to 1.0 ng/mL · h with serum aldosterone more than or equal to 6 ng/dL. PA was confirmed by a 24-hour urinary aldosterone excretion more than or equal to 12 mcg with urinary sodium more than 200 mmol. Results: Only 33% (79/241) of participants with an ARR more than 20 had a positive PA screen on HS. On LS, 56% (44/79) of these participants no longer met criteria for positive PA screening. When compared with participants with positive PA screening on both diets, participants with a positive screen on HS but negative on LS exhibited a significantly higher PRA on both diets. Remarkably, of the 48/79 participants who had PA confirmed, 52% had negative PA screening on LS. The distinguishing feature of these participants with “discordant” screening results was a larger rise in PRA on LS resulting in normalization of the ARR and higher Caucasian race prevalence. Conclusions: Sodium restriction is recommended in hypertension; however, it can significantly raise PRA, normalize the ARR, and result in false interpretation of PA screening. Milder phenotypes of PA, where PRA is not as suppressed, are most susceptible to dietary sodium influences on renin and ARR. Optimal screening for PA should occur under conditions of HS.

scholarly journals SUN-189 A Case of Delayed Hypoaldosteronism Following Unilateral Adrenalectomy for Primary Aldosteronism

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Julie Schommer ◽  
Amal A Shibli-Rahhal
Keyword(s):  
Adrenal Gland ◽  
Plasma Renin Activity ◽  
Potassium Chloride ◽  
Primary Aldosteronism ◽  
Plasma Renin ◽  
Renin Activity ◽  
Endocrine Society ◽  
Unilateral Adrenalectomy ◽  
One Year ◽  
Aldosterone To Renin Ratio

Abstract BACKGROUND: Hypoaldosteronism occurs in 6–30% of patients following unilateral adrenalectomy for primary aldosteronism. The Endocrine Society guidelines recommend discontinuing potassium supplementation and spironolactone postoperatively with repeat renin and aldosterone after surgery to monitor for cure. Clinical Case: A 69-year-old male with a 15-year history of hypertension on amlodipine 10 mg daily, atenolol 100 mg daily, terazosin 5 mg daily, valsartan 160 mg daily, spironolactone 50 mg three times daily, with longstanding hypokalemia on potassium chloride 20 mEq four times daily presented with an ischemic stroke and persistent hypertension (BP 182/79). Following discontinuation of spironolactone, evaluation revealed aldosterone concentration of 214 ng/dL (normal 4.0 - 31) and plasma renin activity of 0.1 ng/mL/hr (normal 0.5 - 4.0), giving an aldosterone-to-renin ratio of 2,140. CT of the abdomen showed a 3 cm right adrenal mass. He underwent uncomplicated right adrenalectomy for primary aldosteronism. Postoperative potassium was 3.4 mEq/L (normal 3.5–5.0) and hypertension persisted, so he was discharged on potassium chloride 10 mEq, losartan 100 mg daily, amlodipine 10 mg daily, and labetalol 200 mg twice daily. Two weeks later potassium level was 5.1 mEq/L and potassium chloride supplement was discontinued. Six months postoperatively, potassium was 5.7 mEq/L with well-controlled blood pressure, so losartan was discontinued. Labs over the subsequent several weeks showed persistent hyperkalemia up to 6.2 mEq/L and new hyponatremia to 128 mEq/L (normal 134 - 150). Repeat plasma renin activity was 0.51 ng/mL/hr and aldosterone concentration &lt;1.0 ng/dL. Morning cortisol concentration was 18.3 ug/dL (normal 6.7 - 22.6) and ACTH 38 pg/mL (normal 6.0 - 50 pg/mL). He was diagnosed with postsurgical hypoaldosteronism. Potassium stabilized at 5.1 mEq/L and sodium stabilized at 134 mEq/L, so he was monitored without treatment for hypoaldosteronism. One year postoperatively his labs showed: potassium 5.1 mEq/L, sodium 135 mEq/L, renin 1.0 ng/mL/hr, and aldosterone 5.7 ng/dL. Conclusion: This patient had primary aldosteronism leading to suppression of aldosterone secretion from the contralateral healthy adrenal gland. This resulted in postoperative hypoaldosteronism once the affected adrenal gland was resected. This case demonstrates the need for continued monitoring of potassium, sodium, renin, and aldosterone following unilateral adrenalectomy for primary aldosteronism, especially in the setting of postoperative angiotensin receptor blocker use or other medications which can affect the renin-angiotensin-aldosterone system.

scholarly journals OR25-06 Morning ACTH Levels as a Reliable Biomarker for Excluding Autonomous Cortisol Secretion in Incidetally Discovered Adrenal Adenomas. A Prospective Cohort

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Roberto Ignacio Olmos ◽  
Stefano Pietro Macchiavello ◽  
Anand Vaidya ◽  
Consuelo Robles ◽  
Javiera Gutierrez ◽  
...  
Keyword(s):  
Negative Predictive Value ◽  
Likelihood Ratio ◽  
Predictive Value ◽  
Prospective Cohort ◽  
Adrenal Adenoma ◽  
Negative Likelihood Ratio ◽  
Inverse Association ◽  
Cortisol Secretion ◽  
Morning Cortisol ◽  
Autonomous Cortisol Secretion

Abstract Adrenal incidentalomas are common with a prevalence of 3-10% and in up to 30% of cases may have probable autonomous cortisol secretion. Hypercortisolism is associated with substantial cardiometabolic morbimortality and can physiologically decrease ACTH levels. Objective: To determine the sensitivity, specificity, and positive and negative predictive values of ACTH levels in evaluating autonomous cortisol secretion in a prospective cohort of incidentally discovered adrenal adenomas. Methods: We prospectively evaluated 224 consecutive adult subjects with incidentally discovered adrenal masses on computed tomography. Finally, 168 participants with radiographic adenoma criteria underwent systematic hormonal assessment, including measurements of morning cortisol and ACTH on day 1, and a 1 mg dexamethasone suppression test (DST) on day 2. Hypercortisolism was excluded if the DST was &lt; 1.8 mcg/dL. Autonomous cortisol secretion was defined as a DST &gt; 5.0 mcg/dL and DST levels of 1.8-5.0 mcg/dL were considered to be possibly autonomous hypercortisolism. We evaluated the correlation of ACTH levels with clinical, radiographic, and endocrine variables. In order to identify the most sensitive threshold value for diagnosing autonomous cortisol secretion, we determined ROC curves and negative likelihood ratio (NLR). Concordance of repeated ACTH was assessed using Bland Altman analysis. Results: The characteristics of the cohort were mean age 56 (+/- 11.8) years, 76% female, adenoma size 19 (+/- 7) mm, and 13% bilateral adenomas. Mean ACTH was 15 (+/- 11) pg/ml (range 5-72) and the mean DST was 2.2 (+/- 3.0) ug/dL (range 0.4-25.9). Fifty-four (32%) participants had a DST ≥1.8mcg/dL and 13 (8%) a DST≥5.0 mcg/dL. We found no correlation between ACTH levels and age, gender or body mass index. ACTH was inversely associated with adrenal adenoma diameter (r=-3.3 p=0.002) and volume (r=-2.9 p=0.008). There was an inverse association between ACTH and DST values (r=-3.1 p=0.01). In the subgroup of patients with a second ACTH measurement we found high concordance, with mean difference of 0.16+/-3.6 pg/ml (p=0.83). ROC analysis showed that an ACTH ≥20 pg/ml had a sensitivity of 98% to exclude hypercortisolism, with a negative predictive value of 97% and a negative likelihood ratio of 0.06. The only case with DST≥1.8 and ACTH≥20 had Cushing′s phenotype with both an adrenal adenoma and a pituitary ACTH-producing adenoma. Systematic evaluation of morning cortisol and ACTH allowed the detection of 5 cases of false negative low DST values due to the use of non-oral corticosteroids. Conclusion: In this cohort, an ACTH ≥20pg/ml excluded autonomous cortisol secretion with excellent sensitivity and negative predictive value, providing strong reassurance that there is no clinically relevant hypercortisolism. Therefore, subjects with a normal DST and ACTH ≥20pg/ml should be candidates for relaxed surveillance.

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