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

Acta Endocrinologica ◽

10.1530/eje-20-0033 ◽

2020 ◽

Vol 183 (3) ◽

pp. 335-341

Author(s):

Henrik Olsen ◽

Albin Kjellbom ◽

Magnus Löndahl ◽

Ola Lindgren

Keyword(s):

Risk Factor ◽

Adrenal Incidentaloma ◽

Cortisol Secretion ◽

Adrenal Incidentalomas ◽

Current Smoking ◽

Established Risk Factor ◽

Case Selection ◽

High Prevalence ◽

Suppression Test ◽

Autonomous Cortisol Secretion

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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Assessment of Plasma-Free Cortisol Concentrations by LC-MS/MS in Patients with Autonomous Cortisol Secretion

Hormone and Metabolic Research ◽

10.1055/a-1661-4126 ◽

2021 ◽

Vol 53 (11) ◽

pp. 752-758

Author(s):

Serkan Yener ◽

Gamze Tuna ◽

Melis Kant ◽

Merve Akis ◽

Ozlem Kara ◽

...

Keyword(s):

Metabolic Profile ◽

Smoking Habit ◽

Free Fraction ◽

Adrenal Incidentaloma ◽

Serum Cortisol ◽

Total Serum ◽

Cortisol Secretion ◽

Cross Sectional ◽

Free Cortisol ◽

Autonomous Cortisol Secretion

AbstractAutonomous cortisol secretion (ACS) of an adrenal incidentaloma (AI) is associated with mild cortisol excess that could result in poor metabolic and cardiovascular outcomes. The biological activity of glucocorticoids depends on the unbound, free fraction. We aimed to evaluate plasma free cortisol (FC) concentrations in patients with ACS in this cross-sectional study. One hundred and ten AI patients in 3 groups; non-functioning (NFA, n=33), possible ACS (n=65), ACS (n=12) were enrolled. Following measurements were conducted: Clinical data and total serum cortisol (TC), plasma corticotrophin (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), cortisol after 1 mg dexamethasone by both immunoassay and LC-MS/MS (DexF), serum corticosteroid binding globulin (CBG), plasma dexamethasone concentration [DEX] and plasma FC by LC-MS/MS. Patients with ACS featured an unfavorable metabolic profile. Plasma [DEX] and serum CBG levels were similar between groups. Plasma FC was significantly higher in ACS when compared to NFA and possible ACS groups p<0.05 and p<0.01, respectively. In multiple regression analysis DexF (beta=0.402, p<0.001) and CBG (beta=−0.257, p=0.03) remained as the independent predictors of plasma FC while age, sex, BMI, smoking habit, and existing cardiovascular disease did not make a significant contribution to the regression model. In conclusion, the magnitude of cortisol excess in ACS could lead to increased plasma FC concentrations. Further studies in AI patients are needed to demonstrate whether any alterations of cortisol affinity for CBG exist and to establish whether plasma FC concentrations predict the unfavorable metabolic profile in ACS.

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Insulin sensitivity in patients with adrenal incidentaloma

Srpski arhiv za celokupno lekarstvo ◽

10.2298/sarh0608315i ◽

2006 ◽

Vol 134 (7-8) ◽

pp. 315-319 ◽

Cited By ~ 5

Author(s):

Miomira Ivovic ◽

Svetlana Vujovic ◽

Zorana Penezic ◽

Milos Zarkovic ◽

Milka Drezgic

Keyword(s):

Insulin Sensitivity ◽

Adrenal Mass ◽

Adrenal Incidentaloma ◽

Regular Insulin ◽

Tolerance Test ◽

Adrenal Tumors ◽

Control Group ◽

Adrenal Incidentalomas ◽

Imaging Methods ◽

Frequent Use

Introduction. Frequent use of modern imaging methods (such as ultrasound, CT and MRI) results in high incidence of accidentally discovered adrenal mass. Adrenal incidentalomas are accidentally discovered adrenal tumors by imaging methods without any prior suspicion of adrenal disease. Some studies have shown decreased insulin sensitivity in patients with adrenal incidentaloma. Objective. The objective of our study was to assess the insulin sensitivity in patients with adrenal incidentalom a. Method. A total of 22 patients with accidentally discovered adrenal mass confirmed by CT/MRI were evaluated in our study. Average age was 53.31?26.5 years and average BMI 25.84?3.65 kg/m2. Control group consisted of 33 healthy subjects. Insulin sensitivity was assessed by short ITT (insulin tolerance test). Blood samples were taken before, 3, 6, 9, 12, 15, 20 and 30 minutes after i.v. bolus of regular insulin (0.05 IU/kg BW). Glycemia was determined by glucose oxidase method. Statistical analysis was done by ANCOVA, using BMI as covariate. Results. Our results showed significantly lower insulin sensitivity in patients with adrenal incidentalomas comparing to the control group (4.95?0.58 vs. 6.62?0.47, p=0.015). Conclusion. Our patients with adrenal incidentalomas manifested lower insulin sensitivity what suggested further follow up and assessment of insulin sensitivity during endocrine evaluation of these patients.

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Adrenal Tumors with Unexpected Outcome: A Review of the Literature

International Journal of Endocrinology ◽

10.1155/2015/710514 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Thomas M. Kerkhofs ◽

Rudi M. Roumen ◽

Thomas B. Demeyere ◽

Antoine N. van der Linden ◽

Harm R. Haak

Keyword(s):

Adrenal Mass ◽

Benign Lesion ◽

Adrenal Incidentaloma ◽

Adrenal Tumors ◽

Diagnostic Challenge ◽

Hormone Production ◽

Imaging Characteristics ◽

Preoperative Diagnostic ◽

Potentially Malignant ◽

Unexpected Outcome

The finding of an adrenal mass should induce a diagnostic work-up aimed at assessing autonomous hormone production and differentiating between benign and (potentially) malignant lesions. The common differential diagnosis in adrenal incidentaloma consists of (non-)functioning adenoma, pheochromocytoma, myelolipoma, metastasis, and primary carcinoma. There remains a category of lesions that are hormonally inactive and display nonspecific imaging characteristics. We provide a succinct literature review regarding pathologies from this category. Imaging and histological characteristics are discussed, as well as clinical management. In conclusion, an adrenal mass may present a diagnostic challenge. After exclusion of most common diagnoses, it can be difficult to differentiate between possible pathologies based on preoperative diagnostic tests. Surgical resection of possibly harmful tumors is indicated, for example, lesions with malignant potential or risk of spontaneous hemorrhage. Resection of an obviously benign lesion is not necessary, unless problems due to tumor size are expected.

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Atypical Adrenocortical Incidentaloma Causing Autonomous Cortisol Secretion and Cardiovascular Complications

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.237 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A118-A118

Author(s):

Salem Gaballa ◽

Areeka Memon ◽

Marigny Roberts

Keyword(s):

Diabetes Mellitus ◽

Myocardial Infarction ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Adrenal Mass ◽

Adrenal Incidentaloma ◽

Cortisol Secretion ◽

Autonomous Cortisol Secretion ◽

Urine Cortisol

Abstract Introduction: Autonomous cortisol secretion (ACS) is found in approximately 10% of patients with an adrenocortical incidentaloma (AI). The majority of these cases are due to non-ACTH-dependent ACS. 2% of patients with AI have adrenocortical cancer. ACS is associated with cardiovascular morbidity, includes arterial stiffness, hypertension, coronary heart disease, and fatal or nonfatal myocardial infarction. Case presentation: A 62-year-old Caucasian male with a history of hypertension (HTN), hyperlipidemia (HLD) and poorly controlled type-2 diabetes mellitus (T2DM) and a recent myocardial infarction (MI) status post (s/p) coronary artery bypass graft (CABG) who presented to the endocrine clinic for evaluation of left adrenal mass. Family history was significant for adrenal carcinoma of his brother at the age of 60. The patient denied any facial flushing, palpitations, tremors, heat or cold intolerance, abnormal sweating, diarrhea, constipation, abdominal pain, recent weight change. Physical examination was unremarkable except midline sternal scar s/p CABG. Vital signs were remarkable for a blood pressure of 142/90. Labs were unremarkable. CT adrenal revealed a left adrenal mass 4.9 x 3.5 x 2.3 cm with HU -3 to 28 heterogeneous. HbA 1C was 8.2 %. Adrenal incidentaloma workup revealed a normal 24-hour urine cortisol level of 29 mcg, abnormal mid-night salivary cortisol of 0.13 mcg/dL and 0.31 mcg/dL, elevated cortisol after 1 mg dexamethasone suppression test (DST) of 343 mcg/dL, elevated cortisol after 8 mg DST of 90 mcg/dL, normal metanephrines of 10 pg/mL and normal normetanephrine of 49 pg/mL, normal aldosterone of 6.1 ng/dL, normal renin activity of 0.36 ng/ml/hr (Aldo/ PRA ratio 16). ACTH was 4.5 pg/ml. The endocrine surgeon was consulted for left adrenalectomy. The pathology showed atypical adrenal cortical neoplasm which does not clearly fulfill the criteria for adrenal cortical carcinoma confirmed by two pathologists. Upon six months follow-up, a 24-hour urine cortisol level was normal, 1mg overnight DST was normal, and no evidence of left adrenal on adrenal CT. Discussion: Adrenal incidentaloma (AI) is a common endocrine diagnosis affecting ~2% of the general population. Up to 10% of patients with AI have autonomous secretion of adrenal hormones. Pheochromocytoma and autonomous cortisol secretion should be excluded in every case and aldosteronism in patients with underlying hypertension and/or hypokalemia. ACS in patients AI has been associated with hypertension, insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome, coronary artery disease, and increased mortality. Adrenalectomy is recommended for patients with a functional unilateral adenoma, with clinically significant hormone excess. Metabolic improvement after adrenalectomy, including weight loss, blood pressure lowering, glucose tolerance, lower lipids have been reported.

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