High prevalence of smoking in patients with adrenal incidentalomas: causality or case selection?

Objective: Autonomous cortisol secretion and possible autonomous cortisol secretion (ACS/pACS) are associated to an increase of cardiovascular risk factors such as hypertension, diabetes mellitus and dyslipidaemia. To our knowledge, the prevalence of smoking, another well-established risk factor for cardiovascular disease, has not been studied in detail in people with ACS/pACS or adrenal incidentalomas. Methods: Patients with adrenal incidentalomas were examined with the 1-mg overnight dexamethasone suppression test (cortisolONDST). Information about current smoking was collected from the patient’s records. Results: We studied 1044 patients, of whom 370 (35%) were current smokers. Of these, 22% had bilateral AI compared to 12% of the non-smokers (P < 0.001). Among patients with unilateral adrenal incidentalomas, smokers had larger adrenal incidentalomas than non-smokers (22 mm vs 19 mm, P < 0.001). Smokers also more often had cortisolONDST ≥50 nmol/L than non-smokers, 54% vs 40% (P < 0.001), a finding independent of the size of the adrenal incidentaloma in patients with unilateral adrenal incidentalomas. Conclusions: In the present study of patients with adrenal incidentalomas, the prevalence of current smoking was higher than in the general population. Furthermore, smokers had larger unilateral adrenal incidentalomas, more often bilateral adrenal incidentalomas, and more frequently ACS/pACS. Whether smoking is a risk factor for adrenal incidentalomas and ACS/pACS or our findings are due to case selection needs to be further studied.

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

Acta Endocrinologica ◽

10.1530/eje-16-0467 ◽

2016 ◽

Vol 175 (2) ◽

pp. G1-G34 ◽

Cited By ~ 444

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

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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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Approach to the patient with adrenal incidentaloma

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab512 ◽

2021 ◽

Author(s):

Irina Bancos ◽

Alessandro Prete

Keyword(s):

Adrenal Mass ◽

Young Patients ◽

Adrenal Incidentaloma ◽

Current Evidence ◽

Adrenal Tumors ◽

Cortisol Secretion ◽

Adrenal Incidentalomas ◽

Cross Sectional ◽

Imaging Characteristics ◽

Autonomous Cortisol Secretion

Abstract Adrenal tumors are commonly discovered incidentally, on cross-sectional abdominal imaging performed for reasons other than adrenal mass. Incidence of adrenal tumors increased 10-fold in the last two decades, with most diagnosed in older adults. In any patient with a newly discovered adrenal mass determining whether the adrenal mass is malignant and whether it is hormonally active is equally important to guide the best management. Malignancy is diagnosed in 5-8% of patients with adrenal tumors, with a higher risk in young patients, if history of extra-adrenal malignancy, in those with large adrenal tumors with indeterminate imaging characteristics, and in bilateral adrenal tumors. While overt hormone excess is uncommon in adrenal incidentalomas, mild autonomous cortisol secretion can be diagnosed in up to 30-50% of patients. As autonomous cortisol secretion is associated with increased cardiovascular morbidity and metabolic abnormalities, all patients with adrenal incidentalomas require work up with dexamethasone suppression test. Management of adrenal tumors varies based on etiology, associated comorbidities, and patient’s preference. This article reviews the current evidence on the diagnosis and evaluation of patients with adrenal mass and focuses on management of the most common etiologies of adrenal incidentalomas.

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Predictors of Tumour Growth and Autonomous Cortisol Secretion Development during Follow-Up in Non-Functioning Adrenal Incidentalomas

Journal of Clinical Medicine ◽

10.3390/jcm10235509 ◽

2021 ◽

Vol 10 (23) ◽

pp. 5509

Author(s):

Marta Araujo-Castro ◽

Paola Parra Ramírez ◽

Cristina Robles Lázaro ◽

Rogelio García Centeno ◽

Paola Gracia Gimeno ◽

...

Keyword(s):

Tumour Growth ◽

Serum Cortisol ◽

Cortisol Secretion ◽

Adrenal Incidentalomas ◽

Specific Data ◽

Tumour Diameter ◽

Suppression Test ◽

Autonomous Cortisol Secretion ◽

Initial Imaging

Purpose: To assess the risk of developing autonomous cortisol secretion (ACS) and tumour growth in non-functioning adrenal incidentalomas (NFAIs). Methods: Multicentre retrospective observational study of patients with NFAIs. ACS was defined as serum cortisol >1.8 µg/dL after 1 mg-dexamethasone suppression test (DST) without specific data on Cushing’s syndrome. Tumour growth was defined as an increase in maximum tumour diameter >20% from baseline; and of at least 5 mm. Results: Of 654 subjects with NFAIs included in the study, both tumour diameter and DST were re-evaluated during a follow-up longer than 12 months in 305 patients. After a median follow-up of 41.3 (IQR 24.7–63.1) months, 10.5% of NFAIs developed ACS. The risk for developing ACS was higher in patients with higher serum cortisol post-DST levels (HR 6.45 for each µg/dL, p = 0.001) at diagnosis. Significant tumour growth was observed in 5.2% of cases. The risk of tumour growth was higher in females (HR 10.7, p = 0.004). Conclusions: The frequency of re-evaluation with DST in NFAIs during the initial 5 years from diagnosis can probably be tailored to the serum cortisol post-DST level at presentation. Re-evaluation of NFAIs with imaging studies, on the other hand, seems unnecessary in most cases, particularly if the initial imaging demonstrates features specific to typical adenoma, given the low rate of significant tumour growth.

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