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 1 mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50 nmol/L (1.8 µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1 mg dexamethasone >138 nmol/L (>5 µg/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 www.eje-online.org European Journal of Endocrinology175:2 G2 Clinical Practice Guideline M Fassnacht and others ESE and ENSAT guideline on adrenal incidentalomawith 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 inciden...

We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 μg) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (∼8 mg/m(2)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease.

Adrenal insufficiency is caused by either primary adrenal failure (mostly due to autoimmune adrenalitis) or by hypothalamic-pituitary impairment of the corticotropic axis (predominantly due to pituitary disease). It is a rare disease, but is life threatening when overlooked. Main presenting symptoms such as fatigue, anorexia, and weight loss are non-specific, thus diagnosis is often delayed. The diagnostic work-up is well established but some pitfalls remain, particularly in the identification of secondary adrenal insufficiency. Despite optimised life-saving glucocorticoid-replacement and mineralocorticoid-replacement therapy, health-related quality of life in adrenal insufficiency is more severely impaired than previously thought. Dehydroepiandrosterone-replacement therapy has been introduced that could help to restore quality of life. Monitoring of glucocorticoid-replacement quality is hampered by lack of objective methods of assessment, and is therefore largely based on clinical grounds. Thus, long-term management of patients with adrenal insufficiency remains a challenge, requiring an experienced specialist. However, all doctors should know how to diagnose and manage suspected acute adrenal failure.

Evidence-linked consensus statements with regard to the diagnosis and management of corticosteroid deficiency in critically ill patients have been developed by a multidisciplinary, multispecialty task force.