What additional workup is needed for a patient with a history of adrenal insufficiency (AI) treated with hydrocortisone (cortisol) who has an incidental finding of an adrenal mass on a chest computed tomography (CT) scan?

Workup for Incidental Adrenal Mass in Patient with Adrenal Insufficiency

Despite the patient's existing adrenal insufficiency and hydrocortisone treatment, comprehensive hormonal evaluation and imaging characterization are still required, with the critical exception that cortisol screening should be omitted since the patient is already on glucocorticoid replacement therapy. 1

Immediate Imaging Characterization Required

Obtain a non-contrast CT of the adrenal mass to measure Hounsfield Units (HU) as the essential first step in determining if this mass is benign or requires further investigation. 1, 2

• If the mass measures <10 HU and is homogeneous and well-circumscribed, it is definitively a benign lipid-rich adenoma requiring no further imaging workup 1, 2
• If the mass measures >10 HU, proceed to second-line imaging with either washout CT or chemical shift MRI to further characterize the lesion 1
• Be aware that approximately 1/3 of pheochromocytomas can demonstrate washout characteristics mimicking adenomas, and malignant masses can occasionally washout in the adenoma range 1

Modified Hormonal Evaluation Protocol

Skip Cortisol Testing

Do not perform dexamethasone suppression testing or other cortisol screening in this patient, as they already have diagnosed adrenal insufficiency and are on replacement therapy. 1, 2 The standard recommendation to screen all adrenal incidentalomas for autonomous cortisol secretion does not apply when the patient has established adrenal insufficiency 1

Essential Hormonal Screening Still Required

Screen for pheochromocytoma with plasma or 24-hour urinary metanephrines, especially if the mass has >10 HU on non-contrast CT or if the patient has any symptoms of catecholamine excess (headaches, palpitations, sweating, anxiety attacks). 1, 2

• This testing is critical before any invasive procedure including biopsy to avoid precipitating a hypertensive crisis 1, 3
• Even if the mass appears benign radiologically, approximately 5% of radiologically benign incidentalomas have subclinical hormone production requiring treatment 2, 4

Check aldosterone-to-renin ratio only if the patient has hypertension and/or hypokalemia. 1, 2

Measure serum androgens (DHEA-S, testosterone, androstenedione) if there are clinical signs of virilization or if adrenocortical carcinoma is suspected based on imaging. 1

Size-Based Management Algorithm

For masses <3 cm:

• Most are benign and extensive workup is not justified in patients without cancer history 1, 2
• If benign-appearing (<10 HU) and non-functional on hormonal testing, no further follow-up imaging or functional testing is required 1, 2

For masses 3-5 cm:

• Consider follow-up CT, additional imaging characterization, or surgical consultation depending on imaging characteristics and hormonal function 1

For masses >5 cm:

• Should be removed due to higher risk of malignancy (up to 6.3% when HU >20) 1

Multidisciplinary Consultation Threshold

Maintain a low threshold for multidisciplinary review involving endocrinology, surgery, and radiology when:

• Imaging is not consistent with a benign lesion 1
• Evidence of hormone hypersecretion is found (pheochromocytoma, aldosteronoma) 1
• The tumor grows significantly during follow-up (>5 mm/year) 1, 5
• Adrenal surgery is being considered 1

Critical Pitfalls to Avoid

Do not perform adrenal mass biopsy routinely—it is rarely indicated and carries unnecessary risks including tumor seeding and potential hypertensive crisis if pheochromocytoma is present. 1, 2

Do not assume the incidental mass is related to the patient's existing adrenal insufficiency without proper evaluation. The patient's adrenal insufficiency could be from autoimmune destruction, prior surgery, or other causes affecting different adrenal tissue than this new mass 6

Do not skip hormonal evaluation even if the mass appears benign on imaging, as approximately 5% of radiologically benign incidentalomas have subclinical hormone production. 2, 4 However, cortisol testing specifically should be omitted in this patient with known adrenal insufficiency 1

Avoid unnecessary repeated imaging for small masses with confirmed benign characteristics (<10 HU, <4 cm, non-functional), as this increases radiation exposure, patient anxiety, and healthcare costs without clinical benefit. 1, 2, 5

Special Consideration for This Patient Population

The patient's existing adrenal insufficiency requiring hydrocortisone replacement suggests significant adrenal dysfunction, but this does not preclude the development of a separate adrenal mass (adenoma, pheochromocytoma, or rarely malignancy) in remaining adrenal tissue 6. The workup proceeds as outlined above with the single modification of omitting cortisol excess screening 1, 2