: 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.