Adrenal Incidentaloma Guidelines

Updated: Jan 12, 2022
  • Author: George T Griffing, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Guidelines Summary


Guidelines issued in 2009 by the American Association of Clinical Endocrinologists (AACE) and American Association of Endocrine Surgeons (AAES) for the management of adrenal incidentalomas recommend that evaluation of patients with an adrenal incidentaloma include clinical, biochemical, and radiographic testing for the following [18] :

  • Hypercortisolism

  • Aldosteronism (if hypertensive)

  • Pheochromocytoma or a malignant tumor

The simplest screening test for autonomous cortisol secretion from an incidentaloma is a 1-mg overnight dexamethasone suppression test. Salivary cortisol, dexamethasone suppression, and urine free cortisol testing can be used if clinical suspicion is high (eg, in patients with hypertension, obesity, diabetes mellitus, or osteoporosis).

Primary aldosteronism is confirmed by lack of aldosterone suppression on a 24-hour urine study with salt loading.

To determine the incidentaloma subtype, high-resolution CT scanning should be performed in all patients. In addition, adrenal venous sampling should be performed in most patients older than 40 years.

Clinical practice guidelines for adrenal incidentaloma management issued in 2016 by the European Society of Endocrinology, in collaboration with the European Network for the Study of Adrenal Tumors (ENSAT), include the following diagnostic recommendations [53] :

  • That clinicians aim to establish if an adrenal mass is benign or malignant at the time of initial detection
  • That all adrenal incidentalomas undergo an imaging procedure to determine if the mass is homogeneous and lipid-rich and therefore benign; for this purpose, the use of noncontrast CT scanning is recommended
  • That every patient with an adrenal incidentaloma undergo careful assessment, including clinical examination, for symptoms and signs of adrenal hormone excess
  • That all patients with adrenal incidentalomas undergo a 1-mg overnight dexamethasone suppression test to exclude cortisol excess
  • That post-dexamethasone serum cortisol levels between 51 and 138 nmol/L (1.9-5.0 µg/dL) be considered evidence of possible autonomous cortisol secretion and that post-dexamethasone cortisol levels of over 138 nmol/L (over 5.0 µg/dL) be taken as evidence of autonomous cortisol secretion
  • That pheochromocytoma be excluded by measurement of plasma-free metanephrines or urinary fractionated metanephrines
  • That in patients with concomitant hypertension or unexplained hypokalemia, the aldosterone/renin ratio be used to exclude primary aldosteronism
  • That sex hormones and steroid precursors be measured in patients with clinical or imaging features suggestive of adrenocortical carcinoma
  • That if the adrenal mass is indeterminate on noncontrast CT scan and the results of the hormonal workup do not indicate significant hormone excess, three options be considered by a multidisciplinary team acknowledging the patient’s clinical context: immediate additional imaging with another modality, interval imaging in 6-12 months (noncontrast CT or MRI scan), or surgery without further delay

For evaluation of possible adrenocortical carcinomas, the 2012 European Society for Medical Oncology (ESMO) guidelines utilize the 2005 proposed diagnostic workup of ENSAT. The guidelines note that although the evidence level for this workup is low, the diagnostic accuracy is high. The recommended workup includes the following tests. [54]

Hormonal work-up

These studies include the following:

  • Glucocorticoid excess (minimum 3 of 4 tests)
  • Dexamethasone suppression test (1 mg, 23:00 h)
  • Excretion of free urinary cortisol (24 h urine)
  • Basal cortisol (serum)
  • Basal adrenocorticotropic hormone (ACTH) (plasma)

Sexual steroids and steroid precursors

These studies include the following:

  • Dehydroepiandrosterone-S (serum)
  • 17-OH-progesterone (serum)
  • Androstenedione (serum)
  • Testosterone (serum)
  • 17-beta-estradiol (serum, only in men and postmenopausal women)
  • 24-hour urine steroid metabolite examination

Mineralocorticoid excess

These studies include the following:

  • Potassium (serum)
  • Aldosterone/renin ratio (only in patients with arterial hypertension and/or hypokalemia)

Catecholamine excess

These studies include the following:

  • Normetanephrine, metanephrine, and methoxytyramine (plasma)
  • Alternatively: fractionated metanephrine excretion (24-h urine)


These studies include the following:

  • CT or MRI scan of abdomen and CT thorax scan
  • Bone scintigraphy (when suspecting skeletal metastases)
  • Fluorodeoxyglucose-PET (FDG-PET) scan (optional)
  • MIBG scintigraphy, DOTATATE-PET scan, or dopa/dopamine PET scan if pheochromocytoma is proved 


The National Comprehensive Cancer Network (NCCN) guidelines recommend staging adrenal cancer according to the 7th edition of the American Joint Committee on Cancer's AJCC Cancer Staging Manual. [55]  However, the European Society of Medical Oncology (ESMO) recommends the 2009 European Network for the Study of Adrenal Tumors (ENSAT) tumor/node/metastasis (TNM) system [56] over the AJCC system. [54]


AACE/AAES guidelines treatment recommendations include the following [18] :

  • Surgical resection should be reserved for those with worsening hypertension, abnormal glucose tolerance, dyslipidemia, or osteoporosis

  • In patients with primary aldosteronism and a unilateral source of aldosterone excess, laparoscopic total adrenalectomy is preferred over open approaches

  • Patients with bilateral idiopathic hyperaldosteronism (IHA) should be managed with selective and nonselective mineralocorticoid receptor blockers

  • Open adrenalectomy should be performed if adrenocortical carcinoma is suspected

For patients with adrenal incidentalomas who do not fulfill the criteria for surgical resection, the guidelines recommend radiographic reevaluation at 3-6 months and then annually for 1-2 years. Hormonal evaluation should be performed annually for 5 years.

The NCCN guidelines for the treatment of adrenal carcinoma include separate recommendations for localized and metastatic disease. Recommendations for localized disease are as follows [57] :

  • Resection of primary tumor and adjacent lymph nodes

  • Open adrenalectomy recommended

  • External-beam radiation therapy and adjuvant mitotane may be considered in patients at high risk for recurrence

NCCN treatment recommendations for metastatic disease are as follows [57] :

  • Observation for clinically indolent disease with imaging and biomarkers (if functional) every 3 months

  • Resection of primary tumor and metastases if more than 90% removable, particularly if functional

  • Systemic therapy, preferably within a clinical trial

The ESMO guidelines recommendations include the following [54] :

  • Open surgery with transperitoneal access for stages I-III when complete resection is possible

  • Laparoscopic adrenalectomy only for selected patients with small tumors and no evidence of invasiveness or adrenal incidentalomas

  • Margin-free complete resection of locally advanced adrenocortical carcinomas may require resection of parts of adjacent organs

  • Re-resection of adrenocortical carcinomas for recurrence if margin-free resection is possible and the time to recurrence has been over 12 months

  • Adjuvant mitotane therapy in patients with incomplete/R1 or Rx resection and/or Ki67 expression in 10% or less of neoplastic cells

  • For bone metastasis, palliative radiotherapy is an option; arterial chemoembolization and radiofrequency ablation may be beneficial in selected patients

The aforementioned clinical practice guidelines for adrenal incidentaloma management issued in 2016 by the European Society of Endocrinology, in collaboration with ENSAT, include the following surgical recommendations [53] :

  • That adrenalectomy be considered the standard of care for unilateral adrenal tumors with clinically significant hormone excess
  • That surgery not be performed in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies
  • That laparoscopic adrena­lectomy be performed in patients with unilateral adrenal masses with radiologic findings suspicious of malignancy and a diameter of 6 cm or less, but without evidence of local invasion
  • That open adrenalectomy be performed for unilateral adrenal masses with radiologic findings suspicious of malignancy and signs of local invasion
  • That perioperative glucocorticoid treatment be administered at major surgical stress doses as recommended by guidelines, in all patients undergoing surgery for an adrenal tumor in which there is evidence of (possible) autonomous cortisol secretion; ie, in patients who do not suppress to less than 50 nmol/L after 1 mg dexamethasone overnight.