What is the initial workup for an adrenal incidentaloma?

It runs on two tracks. Imaging: a noncontrast CT to see whether the mass is homogeneous and lipid-rich, at 10 Hounsfield units or less. Hormones: a 1 mg overnight dexamethasone suppression test in every patient, plasma or urine metanephrines if the mass is not a typical benign adenoma, and an aldosterone-to-renin ratio if there is hypertension or unexplained hypokalemia. Sex steroids are measured only if carcinoma is suspected.

What does 10 Hounsfield units mean on an adrenal CT?

Hounsfield units describe how dense tissue appears on CT. Lipid-rich adrenal adenomas look dark, at 10 HU or less on a noncontrast scan. Under the 2023 European Society of Endocrinology guideline, a homogeneous mass at or below 10 HU is benign whatever its size and needs no further imaging, and it is unlikely enough to be a pheochromocytoma that metanephrine testing is not required.

What is mild autonomous cortisol secretion?

Mild autonomous cortisol secretion (MACS) is the 2023 ESE term for a cortisol above 1.8 µg/dL (50 nmol/L) after a 1 mg dexamethasone test in a patient without overt Cushing syndrome. ACTH independence should be confirmed and the test repeated. MACS rarely progresses to overt Cushing syndrome, but it is linked to hypertension, type 2 diabetes and vertebral fractures, which should be screened for.

When should an adrenal incidentaloma be removed?

The 2023 ESE guideline recommends adrenalectomy for a unilateral tumor with clinically significant hormone excess, such as a pheochromocytoma, an aldosterone-producing adenoma or a cortisol-secreting adenoma, and for masses whose imaging suggests cancer, usually after multidisciplinary review. Surgery can be considered for MACS with relevant comorbidities. It recommends against surgery for an asymptomatic, nonfunctioning mass that looks clearly benign.

Why is adrenal biopsy usually avoided?

Biopsy rarely changes management and carries specific risks: puncturing a pheochromocytoma can trigger a hypertensive crisis, and sampling an adrenocortical carcinoma can spread tumor. The 2023 ESE guideline reserves biopsy for some patients with cancer elsewhere, and only when the mass is hormonally inactive with pheochromocytoma excluded, is not clearly benign on imaging, and the result would change treatment.

Adrenal Incidentaloma Workup: CT, DST & Metanephrines

An adrenal incidentaloma is an adrenal mass found on imaging done for another reason, and the workup answers two questions: is it benign, and is it making hormones? Under the 2023 European Society of Endocrinology (ESE)/ENSAT guideline, start with a noncontrast CT: a homogeneous mass of 10 Hounsfield units (HU) or less is a benign, lipid-rich adenoma and needs no more imaging, whatever its size. Every patient gets a 1 mg overnight dexamethasone suppression test (a cortisol of 1.8 µg/dL or less excludes autonomous cortisol secretion); plasma or urine metanephrines are needed when the mass is not a typical benign adenoma; and an aldosterone-to-renin ratio is added for hypertension or unexplained hypokalemia. Pheochromocytoma must be excluded before any biopsy is considered.

The workup at a glance (ESE/ENSAT 2023)

Question	Test	Reassuring result	Abnormal result → next step
Benign or malignant?	Noncontrast CT, the first imaging test	Homogeneous and 10 HU or less: benign; no further imaging	Homogeneous, 11–20 HU and under 4 cm: immediate extra imaging or repeat CT in 12 months. 4 cm or more and either heterogeneous or over 20 HU: multidisciplinary review, staging, usually surgery
Cortisol excess?	1 mg overnight dexamethasone suppression test in every patient (it may be skipped in frail patients with limited life expectancy)	Cortisol 1.8 µg/dL (50 nmol/L) or less	Over 1.8 µg/dL without overt Cushing features = mild autonomous cortisol secretion (MACS): confirm low ACTH, repeat the test, screen for hypertension, type 2 diabetes and vertebral fractures
Pheochromocytoma?	Plasma free or urinary fractionated metanephrines when the mass is not a typical benign adenoma	Normal	Raised: localize, give alpha-blockade, then adrenalectomy
Primary aldosteronism?	Aldosterone-to-renin ratio if hypertension or unexplained hypokalemia	Normal ratio	Confirm with saline infusion or oral salt loading, then adrenal vein sampling to find the side
Adrenocortical carcinoma?	Sex steroids and steroid precursors, only if imaging or clinical features suggest carcinoma	Not needed for benign-looking masses	Staging (chest CT and/or FDG-PET/CT), then surgery by an expert adrenal surgeon

The guideline also recommends discussing a patient in a multidisciplinary team (radiologist, endocrinologist and surgeon) when imaging is not clearly benign, there is hormone excess, surgery is being considered or the mass grows.

Functional causes compared

Condition	Hormone	Classic clues	Screening test	Confirm or treat
Pheochromocytoma	Catecholamines	Episodic headache, sweating and palpitations; paroxysmal or sustained hypertension	Plasma free metanephrines (up to 99% sensitive) or urinary metanephrines	Alpha-blocker (phenoxybenzamine or doxazosin) first, then a beta-blocker, for about 10–14 days before surgery
Cushing syndrome or MACS	Cortisol	Overt: thin skin, easy bruising, striae, muscle weakness. MACS: often only hypertension, diabetes or vertebral fractures	1 mg overnight dexamethasone suppression test	Low or undetectable ACTH points to the adrenal; stress-dose glucocorticoids around adrenalectomy
Primary aldosteronism	Aldosterone	Resistant hypertension; hypokalemia and metabolic alkalosis, though potassium can be normal	Aldosterone-to-renin ratio	Saline infusion or salt loading, then adrenal vein sampling; adenoma: laparoscopic adrenalectomy; bilateral hyperplasia: spironolactone or eplerenone
Adrenocortical carcinoma	Cortisol, androgens, both or none	Large, heterogeneous mass; virilization in a woman	Steroid profile when suspected	Staging and resection by an expert adrenal surgeon
Nonfunctioning adenoma	None	No symptoms	All tests negative	No surgery; no follow-up imaging if 10 HU or less

Merck notes that a significant minority of "nonfunctioning" incidentalomas make some cortisol autonomously, which is why the dexamethasone test is for everyone. Each syndrome has its own deep dive: Conn syndrome and Cushing syndrome vs Cushing disease.

Imaging triage

Noncontrast CT finding	What it usually means	ESE 2023 action
Homogeneous, 10 HU or less, any size	Lipid-rich adenoma	Benign: no further imaging
Homogeneous, 11–20 HU, under 4 cm, no significant hormone excess	Probably benign	Immediate extra imaging (washout CT, chemical-shift MRI or FDG-PET/CT) or noncontrast CT in 12 months
4 cm or more and either heterogeneous or over 20 HU	Relevant risk of malignancy	Multidisciplinary review and staging; usually surgery; imaging in 6–12 months if not operated on
In between: 4 cm or more with 11–20 HU, or under 4 cm with over 20 HU or a heterogeneous look	Indeterminate; cancer still unlikely	Individualized, usually immediate extra imaging
Bilateral masses	Adenomas or hyperplasia, metastases, lymphoma, infection, hemorrhage	Assess each side the same way; 17-hydroxyprogesterone for bilateral hyperplasia; check adrenal function with bilateral metastases, lymphoma, infiltration or hemorrhage

The 17-hydroxyprogesterone check looks for 21-hydroxylase deficiency, reviewed in the congenital adrenal hyperplasia overview.

What changed, and why older answers differ

Metanephrines: the 2016 ESE and 2017 Korean guidelines screened every incidentaloma. ESE 2023 dropped this for masses of 10 HU or less, because such lipid-rich masses are unlikely to be pheochromocytomas. If a question gives no CT density, testing for pheochromocytoma is still the safe choice.
Size: a homogeneous mass of 10 HU or less is benign regardless of size; the old under-4-cm condition was removed.
Cortisol: "possible autonomous cortisol secretion" (1.9–5.0 µg/dL) and "autonomous cortisol secretion" (over 5.0 µg/dL) were merged into MACS, any value over 1.8 µg/dL without overt Cushing features. MACS rarely progresses to overt Cushing syndrome (under 1%).
Follow-up: no repeat hormone testing after a normal first workup unless new signs appear, and no repeat imaging for clearly benign masses. The annual hormone testing for 4–5 years in the 2009 AACE/AAES guideline is not part of the ESE approach. An indeterminate mass that is not removed gets one repeat CT or MRI in 6–12 months, and surgery if it grows more than 20% and at least 5 mm.

Pheochromocytoma, biopsy and surgery pearls

Alpha first, beta second. Unopposed beta-blockade can paradoxically raise blood pressure by blocking beta-mediated vasodilation. Merck pairs phenoxybenzamine or doxazosin with propranolol, allows about 10–14 days to re-equilibrate, and adds a high-salt diet to expand blood volume. The memory hook is in the pheochromocytoma mnemonic.
Biopsy: ESE recommends against adrenal biopsy except in some patients with a history of cancer elsewhere, and only when the mass is hormonally inactive (pheochromocytoma excluded), not clearly benign on imaging, and the result would change management. Biopsy can precipitate a hypertensive crisis in a pheochromocytoma and spread tumor from a carcinoma.
Glucocorticoid cover: give stress-dose glucocorticoids around surgery when the post-dexamethasone cortisol is over 1.8 µg/dL, because the opposite adrenal may be suppressed.
Young or pregnant patients: assess urgently in pregnancy and under age 40, prefer MRI in children, adolescents and pregnancy, and remove masses that stay indeterminate.

Exam traps

Biopsy first is wrong: exclude pheochromocytoma, and usually skip biopsy altogether.
Beta-blocker first in pheochromocytoma is wrong: it can worsen hypertension.
Normal potassium does not exclude primary aldosteronism; any hypertensive patient with an incidentaloma gets an aldosterone-to-renin ratio.
Size alone does not decide malignancy: a 5 cm homogeneous mass of 10 HU or less is still benign.
A significant minority of "nonfunctioning" masses make a little cortisol, so plan stress-dose steroids for surgery when the dexamethasone test is abnormal.
Yearly CT for a benign adenoma is no longer recommended.

Worked example

Vignette. A 58-year-old woman has a CT for renal colic that shows a 2.8-cm homogeneous left adrenal mass with an unenhanced density of 6 HU. She takes amlodipine for hypertension (152/94 mm Hg), and her potassium is 3.2 mEq/L. She has no cushingoid features. Which tests should be ordered now?

Answer: A 1 mg overnight dexamethasone suppression test (for every incidentaloma) and an aldosterone-to-renin ratio (hypertension with hypokalemia). The mass is a benign lipid-rich adenoma, so no further imaging is needed, and under ESE 2023 metanephrines are not required for a mass of 10 HU or less (older guidelines tested everyone).

Why not the others?

CT-guided biopsy: the mass is benign on imaging, and biopsy is reserved for a few patients with cancer elsewhere after pheochromocytoma is excluded.
Repeat CT in 6–12 months: only for indeterminate masses.
Adrenalectomy now: surgery is for proven hormone excess or suspected cancer. If the ratio is high, primary aldosteronism must be confirmed and lateralized with adrenal vein sampling first, because CT cannot reliably show whether the aldosterone comes from this adenoma or from both glands.
24-hour urine vanillylmandelic acid (VMA): outdated; metanephrines are the test when pheochromocytoma screening is needed.

Key takeaways

Two questions: benign? (noncontrast CT) and functioning? (hormones).
Homogeneous and 10 HU or less = benign, at any size, with no follow-up imaging.
1 mg dexamethasone test for everyone; over 1.8 µg/dL without Cushing features = MACS.
Metanephrines when the mass is not a typical adenoma; aldosterone-to-renin ratio for hypertension or unexplained hypokalemia.
4 cm or more and either heterogeneous or over 20 HU → suspect cancer: multidisciplinary review, staging, usually surgery.
No biopsy before pheochromocytoma is excluded; alpha before beta.