06. Adrenal Incidentaloma and Tumors

Definition

Adrenal masses found on imaging, generally 1cm+ in diameter, are relatively common, found in 4% of people on CT. Frequency increases with age. 

Etiology 

  • Benign masses: adenomas (non-functional), lipomas, hematomas, cysts, myelolipomas.
  • Functional masses: pheochromocytoma, mineralocorticoid-secreting tumors (Conn’s syndrome), cortisol-secreting tumors (Cushing’s syndrome).
  • Malignant masses: primary adrenocortical carcinoma (functional or not) or metastatic disease.

Evaluation

Evaluate for malignancy (° in above flowchart)

  • Metastatic disease is usually bilateral and primary tumor usually known. Consider PET.
  • Adenoma vs. carcinoma: adrenocortical carcinoma accounts for 2% of tumors <4 cm, 6% of tumors 4-6 cm, and 25% of tumors >6 cm in size.
    • Benign features: <4 cm, <10 Hounsfield units (HU) on unenhanced CT, smooth margins, homogenous, hypodense appearance, CT contrast-medium washout >50% at 10 minutes.
    • Suspicious features: >4 cm (sensitivity 90%, specificity 24%), >10 HU on unenhanced CT, <40% CT contrast-medium washout at 15 minutes.
  • CT-guided FNA rarely performed, but consider if high risk features or concern for infection. Rule out pheochromocytoma first!

Hormonal testing (* in above flow chart)

Cushing’s syndrome: ~5.3% of incidentalomas; test for this in all patients.

  • Diagnosis is controversial. Likely if two out of the following three tests are abnormal:
    • Dexamethasone suppression test: 1 mg dexamethasone at 11 pm, then check 8 am cortisol the next day. Abnormal value is >1.8 mcg/dL.
    • Late night salivary cortisol (abnormal is >4 nmol/L or 145 ng/dL).
    • 24-hour urinary free cortisol (abnormal is >55mcg/day).
  • If biochemical hypercortisolism is identified, confirm that ACTH is suppressed (as a high ACTH would suggest central Cushing’s disease rather than an adrenal process).

Pheochromocytoma: ~5% of incidentalomas; test for this in all patients. Classic triad is headache (>90%), hypertension (paroxysmal or sustained), and diaphoresis.

  • 24-hour urine fractionated metanephrines and catecholamines: sensitivity and specificity 91-98%. False positives with labetalol (assay interference), TCAs, decongestants.
  • Plasma free metanephrines: sensitivity 96-100%, specificity 85-89%. Low positive predictive value in low-risk populations. Specificity decreases with age.
  • Imaging may be helpful but is not diagnostic.

Hyperaldosteronism: ~1% of incidentalomas; test if patient hypertensive or hypokalemic.

  • Hypokalemia and metabolic alkalosis variably present.
  • Check plasma aldosterone concentration (PAC) and plasma renin activity (PRA), if possible in the morning on a seated patient post ambulation. No uniformity on assay methods or cut offs, but PAC/PRA ratio above 30 is generally thought to be diagnostic. Spironolactone and epleronone must be discontinued in advance, and other antihypertensives may influence results.  

Management

  • Functioning pheochromocytoma: management is surgical, with careful pre-surgical preparation.
    • Volume depleted state requiring significant IV volume expansion.
    • Alpha blockade beginning ~ 2 weeks before surgery (e.g. phenoxybenzamine). Titrate to symptom and blood pressure control.
    • Beta blockade only after adequate alpha blockade (to avoid hypertensive crisis with unopposed alpha agonism).
    • Pheochromocytomas and paragangliomas (extra-adrenal catecholamine producing tumors) are associated with a variety of genetic syndromes and germline mutations (e.g. MEN2, VHL, NF1, SDH). Consider genetics consult for all bilateral pheochromocytomas, onset age <45, positive family history, any paraganglioma.
  • Suspicious masses for malignancy: surgery if patient is able to tolerate; otherwise follow up imaging in 3 months.
  • Benign, non-functioning masses: surgery if size >4 cm or growing on follow-up; otherwise, image at 6, 12, and 24 months and check hormones every year for 4 years.

Key Points 

  • Adrenal incidentalomas are common.
  • If >4cm or malignant characteristics on CT, surgery is recommended (evaluate for pheochromocytoma first).
  • If <4cm, evaluate for Cushing’s, hyperaldosteronism, or pheochromocytoma.

Grumbach MM, Biller BM, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (“incidentaloma”). Ann Intern Med 2003;138:424-429.

Lenders JW, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014. 99(6):1915-42.

Neiman KL. Approach to the patient with an adrenal incidentaloma. J Clin Endocrinol Metab 2010;95(9):4106-13.

Young WF. The incidentally discovered adrenal mass. N Engl J Med 2007;356:601-610.