Adrenal incidentaloma

Definition

An adrenal incidentaloma is an adrenal mass discovered incidentally on imaging performed for another reason, such as abdominal CT or MRI. Every incidentaloma raises two questions: is the mass hormonally active, and is it benign or malignant? Most incidentalomas are non-functioning adrenocortical adenomas.

Classification

Causes

• Adrenal cortex: adenoma (non-functioning or functioning), nodular hyperplasia, adrenocortical carcinoma.
• Adrenal medulla: phaeochromocytoma, ganglioneuroma.
• Other tumors: myelolipoma, lipoma and others.
• Cysts and pseudocysts, hematomas and hemorrhage.
• Metastases, most often from lung cancer, also from breast, kidney and gastrointestinal cancers.
• Pseudo-adrenal masses arising from neighbouring organs.
• Bilateral masses: consider metastases, lymphoma, infections (e.g. tuberculosis, histoplasmosis) and hemorrhage.

Occurrence & epidemiology

Incidentalomas are found in about 1–5 % of cross-sectional imaging studies that include the adrenals and in about 2.3 % of autopsy series. Non-functioning adenomas account for about 70 %. In a large Japanese survey about 25 % were hormonally active: cortisol-producing 10.5 %, aldosterone-producing 5.1 %, catecholamine-producing 8.5 %. Adrenocortical carcinoma was found in 1.4 % and metastases in 3.7 %. With a known current or previous cancer outside the adrenal gland, the proportion of metastases rises to 50–75 %.

Clinical features

Most patients are asymptomatic. However, a significant proportion of apparently non-functioning adenomas secrete cortisol autonomously (mild autonomous cortisol secretion) without the classic Cushing picture; clues are weight gain, hypertension and diabetes mellitus. Cardiometabolic comorbidities are common with both non-functioning adenomas and mild cortisol autonomy.

Adrenal insufficiency is rare and occurs only with bilateral involvement. Massive bilateral hemorrhage presents with abdominal pain, a falling hematocrit and signs of acute adrenal insufficiency. A non-functioning adrenocortical carcinoma usually presents as an infiltrating retroperitoneal process or with metastases.

Diagnosis

Hormonal evaluation

• Cortisol autonomy: overnight dexamethasone suppression test; a serum cortisol of 50 nmol/l (1.8 µg/dl) or more the next morning is considered abnormal.
• Phaeochromocytoma: plasma free metanephrines or 24-hour urinary fractionated metanephrines. The dexamethasone suppression test is done only after phaeochromocytoma has been excluded, because it can provoke a hypertensive crisis in catecholamine-secreting tumors.
• Primary aldosteronism: plasma aldosterone and renin (aldosterone-to-renin ratio).
• Suspected adrenocortical carcinoma: additionally androgens and precursors such as DHEA-S, androstenedione, 17-OH progesterone and 11-deoxycortisol.

Imaging criteria

• Unenhanced CT: an attenuation of 10 HU or less indicates a lipid-rich, benign adenoma; this cut-off is used in current European guidelines.
• Guideline criteria for benignity: diameter below 4 cm and unenhanced attenuation of 10 HU or less.
• Features suggesting malignancy: diameter of 4 cm or more and unenhanced attenuation above 20 HU.
• CT with delayed contrast washout: an absolute washout above 60 % and a relative washout above 40 % suggest an adenoma.
• Chemical-shift MRI: signal loss on opposed-phase images indicates a lipid-rich adenoma.

Additional imaging notes

• Lipid-poor adenomas: at least 30 % of adenomas are lipid-poor and measure above 10 HU; their density then resembles phaeochromocytomas and malignant lesions.
• Size: in a prospective study 98 % of adrenocortical carcinomas measured at least 4 cm; none was smaller than 2 cm.
• Chemical-shift MRI: an alternative, particularly when iodinated contrast cannot be used.
• Fine-needle biopsy: only if metastasis or infection is suspected and only after phaeochromocytoma has been excluded; unsuitable when adrenocortical carcinoma is suspected because of the risk of tumor seeding.

Keep learning in the app

Further reading (open access)

1. MSD Manual Professional: Nonfunctional Adrenal Masses
2. Review of Diagnostic Modalities for Adrenal Incidentaloma (J Clin Med 2023, PMC)
3. StatPearls: Adrenal Adenoma

Cross-references