Laboratory Tests for Adrenal Incidentaloma Follow-up

Core Laboratory Evaluation

The American Urological Association recommends that all patients with adrenal incidentalomas should undergo screening for autonomous cortisol secretion with a 1 mg overnight dexamethasone suppression test 1, 2
A 1 mg overnight dexamethasone suppression test is the preferred initial screening test for autonomous cortisol secretion, with serum cortisol measured at 8 AM the next morning after administering 1 mg dexamethasone at 11 PM 1
The Endocrine Society suggests that a serum cortisol level of ≤50 nmol/L after dexamethasone suppression testing excludes cortisol hypersecretion, while levels between 51-138 nmol/L suggest possible autonomous cortisol secretion, and levels >138 nmol/L indicate evidence of cortisol hypersecretion 1, 3
For patients with hypertension and/or hypokalemia, the American Heart Association recommends screening for primary aldosteronism using the aldosterone/renin ratio, with a ratio >20 ng/dL per ng/mL/hr having excellent sensitivity and specificity for confirming hyperaldosteronism 1, 2
The National Institute of Health recommends that patients with adrenal masses ≥10 HU on non-contrast CT or with symptoms of catecholamine excess should undergo testing for pheochromocytoma using plasma free metanephrines or 24-hour urinary metanephrines and normetanephrines 1, 3, 4
For patients with suspected adrenocortical carcinoma or virilization, the European Society for Medical Oncology recommends serum androgen testing, including DHEAS and testosterone 1, 3, 5

The American College of Endocrinology recommends the following algorithm for laboratory testing:

The American Association of Clinical Endocrinologists notes that medications can interfere with hormone testing results, and considers holding interfering medications before testing when possible 1
The Endocrine Society recommends that patients with mild autonomous cortisol secretion should be monitored for metabolic comorbidities that could be related to cortisol excess, although the strength of this evidence is not specified 1
The European Association of Urology suggests that follow-up hormone testing is not required for benign non-functional adenomas <4 cm, myelolipomas, and other small masses containing macroscopic fat, with a moderate level of evidence supporting this recommendation 4, 6
The American Urological Association recommends that for indeterminate masses, repeat functional testing should be performed if the mass grows >5 mm/year, based on low-quality evidence 6

For adrenal incidentalomas with minimal growth, DHEA sulfate, androstenedione, testosterone, 17-hydroxyprogesterone, and estradiol are not routinely recommended unless there are specific clinical signs of virilization or feminization, as indicated by the American Urological Association 8
For adrenal incidentalomas with growth <3mm/year, no further imaging follow-up or functional testing is required, according to the American Urological Association 9
For lesions growing 3-5mm/year, continued surveillance may be appropriate, but extensive hormonal testing is not indicated, as recommended by the American Urological Association 9
For lesions growing >5mm/year, repeat functional work-up is recommended before considering surgical intervention, as suggested by the American Urological Association 9

The 2023 CUA/AUA guidelines indicate that only about 5.3% of adrenal incidentalomas are cortisol-secreting adenomas, 1% are aldosterone-secreting adenomas, and 5.1% are pheochromocytomas, providing a basis for the American Urological Association's recommendations 10
The risk of malignant transformation in benign-appearing adrenal lesions with minimal growth is extremely low (0-1%), as reported by the American Urological Association 11
Age and imaging characteristics are more important determinants of malignancy risk than minimal growth; young patients (<40 years) with indeterminate imaging features warrant more thorough evaluation, according to the American Urological Association 8
Bilateral adrenal incidentalomas warrant consideration of congenital adrenal hyperplasia with 17-hydroxyprogesterone measurement, but this is not indicated for unilateral masses with minimal growth, as stated by the American Urological Association 9

The American Urological Association recommends first-line imaging with non-contrast CT to determine if the mass is benign or malignant, with benign features including homogeneous, well-circumscribed, <10 Hounsfield Units (HU) 12, 13
For indeterminate masses on non-contrast CT, the guideline suggests proceeding with second-line imaging: washout CT or chemical-shift MRI 14

Surgical intervention is indicated for functional tumors, including unilateral cortisol-secreting masses with clinically apparent Cushing's syndrome, aldosterone-secreting adrenal masses, and pheochromocytomas 14
The American Urological Association recommends surgical intervention for suspicious imaging features, including masses >4 cm with inhomogeneous appearance or >20 HU, and for growth during follow-up, including adrenal incidentalomas growing >5 mm/year (after repeating functional work-up) 13, 14, 15

The guideline recommends follow-up without surgery for benign non-functional lesions <4 cm, myelolipomas, and other small masses containing macroscopic fat, with no further follow-up imaging or functional testing required 14, 15
For radiologically benign (<10 HU) but ≥4 cm non-functional lesions, the guideline suggests repeat imaging in 6-12 months 13, 15

Each lesion in bilateral adrenal incidentalomas should be separately characterized following the same protocol as unilateral masses, and consider measuring serum 17-hydroxyprogesterone to exclude congenital adrenal hyperplasia 13
Adrenal mass biopsy should not be performed routinely for the work-up of an adrenal incidentaloma, but only consider when diagnosis of metastatic disease from an extra-adrenal malignancy would be of value 14

Failing to consider a multidisciplinary approach when imaging is not consistent with a benign lesion, there is evidence of hormone hypersecretion, significant tumor growth, or when surgery is being considered 12, 16