How should incidentally discovered masses (incidentalomas) be evaluated and managed based on size, imaging characteristics, and patient risk factors?

Management of Incidentalomas

All incidentally discovered masses require immediate assessment of both malignancy risk through dedicated imaging characteristics and hormonal activity through biochemical testing, with management algorithms differing substantially based on the organ involved.

Adrenal Incidentalomas

Initial Evaluation

Every patient with an adrenal incidentaloma requires two parallel assessments 1, 2:

Imaging characterization:

• Obtain unenhanced CT with Hounsfield unit (HU) measurement
• Homogeneous lesions with HU ≤10 are definitively benign regardless of size and require no further imaging 2
• Lesions with HU >10 require chemical shift MRI or contrast-enhanced CT
• Lesions >4 cm that are inhomogeneous or have HU >20 carry sufficient malignancy risk to warrant surgery 2

Hormonal work-up (mandatory for all patients):

• Plasma or urinary metanephrines (to exclude pheochromocytoma)
• 1-mg overnight dexamethasone suppression test with cutoff of serum cortisol ≤50 nmol/L (≤1.8 µg/dL) 2
• In hypertensive patients: plasma aldosterone concentration/plasma renin activity ratio 2

Size-Based Management Algorithm

Lesions <4 cm with benign imaging (HU <10):

• No further follow-up imaging or functional testing required 1
• Exception: myelolipomas and masses with macroscopic fat also require no follow-up regardless of size 1

Lesions ≥4 cm with benign imaging (HU <10) but non-functional:

• Repeat imaging in 6-12 months 1
• This reflects the 4 cm threshold where most pheochromocytomas and adrenocortical carcinomas are diagnosed

Growth rate thresholds on follow-up:

• Growth >5 mm/year: Consider adrenalectomy after repeating functional work-up 1
• Growth <3 mm/year: No further imaging or functional testing required 1

Special Populations

Young adults, children, and pregnant patients:

• Adrenal lesions are more likely malignant in these groups 1
• Expedite evaluation using low-dose CT or chemical shift MRI to minimize radiation exposure 1

Bilateral adrenal incidentalomas:

• Characterize each lesion separately using the same criteria as unilateral masses 1
• Additionally measure serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 1
• Assess for adrenal insufficiency if bilateral infiltrative disease, metastases, or hemorrhage suspected 1

Mild Autonomous Cortisol Secretion (MACS)

Patients with post-dexamethasone cortisol >50 nmol/L (>1.8 µg/dL) without overt Cushing's syndrome have MACS and harbor increased morbidity/mortality risk 2:

• Screen for cortisol-related comorbidities: hypertension, type 2 diabetes, osteoporosis
• Consider surgery in patients with MACS who have relevant comorbidities using an individualized approach 2

Indeterminate Lesions

When lesions remain indeterminate despite complete imaging work-up 1:

• Use shared decision-making between patient and clinician
• Options: repeat imaging in 3-6 months versus surgical resection
• Discuss in multidisciplinary expert meeting for lesions >4 cm that are inhomogeneous or HU >20 2

Surgical Indications

Absolute indications for adrenalectomy:

• Pheochromocytoma 1
• Aldosterone-secreting adenomas 1
• Suspected adrenocortical carcinoma 1
• Lesions >6 cm 3
• Lesions >4 cm meeting additional malignancy criteria 3

Surgical approach:

• Minimally invasive surgery (MIS) when feasible 1
• European Society of Endocrinology suggests 6 cm cutoff for open versus laparoscopic approach for suspected adrenocortical carcinoma, though this lacks high-quality evidence 1

Pituitary Incidentalomas

The 2025 Pituitary Society guidelines provide distinct management for pituitary lesions 4:

Macroadenomas (≥10 mm):

• Require endocrinology consultation, dedicated pituitary MRI, comprehensive hormone testing, and visual field assessment
• Surgical resection indicated for lesions causing mass effect or hormone hypersecretion

Microadenomas (<10 mm):

• Nearly always clinically non-functioning with low likelihood of hormonal deficits
• Generally managed with observation rather than intervention
• Regular monitoring for growth or development of symptoms

Special consideration:

• Consultation with multidisciplinary pituitary center recommended for new/deteriorating symptoms, when surgery considered, or management uncertainty 4

Key Pitfalls to Avoid

1. Do not skip hormonal work-up: Even asymptomatic pheochromocytomas can cause significant morbidity; plasma/urinary metanephrines are mandatory for all adrenal incidentalomas 2

2. Do not use size alone for malignancy assessment: A 5 cm homogeneous lesion with HU <10 is benign, while a 3 cm heterogeneous lesion with HU >20 requires multidisciplinary discussion 2

3. Do not ignore MACS: Post-dexamethasone cortisol >50 nmol/L carries increased morbidity/mortality risk even without overt Cushing's syndrome 2

4. Do not apply adrenal guidelines to other organs: Pituitary incidentalomas follow completely different management algorithms 4

5. Age matters: Higher suspicion for malignancy in young adults, children, and pregnant patients with adrenal masses 1