What is the recommended approach for a hormonal workup in a patient with adrenal nodules?

Recommended Hormonal Workup for Adrenal Nodules

All patients with adrenal nodules should undergo a comprehensive hormonal evaluation including screening for cortisol excess, catecholamine excess, and in specific cases, aldosterone and androgen excess. 1

Initial Hormonal Assessment

Cortisol Evaluation

• All patients with adrenal incidentalomas must be screened for autonomous cortisol secretion regardless of clinical symptoms 1
• The preferred screening test is the 1 mg overnight dexamethasone suppression test (DST) with a cortisol cutoff value of ≤50 nmol/L (≤1.8 μg/dL) to rule out cortisol excess 1, 2
• Patients with serum cortisol >50 nmol/L (>1.8 μg/dL) after DST may have mild autonomous cortisol secretion (MACS) and should be evaluated for cortisol-related comorbidities such as hypertension and diabetes 2

Catecholamine Evaluation

• For all adrenal masses, pheochromocytoma must be systematically ruled out due to risk of life-threatening crises if not identified before interventions 1
• Recommended screening tests:
  • Plasma-free metanephrines OR urinary-fractionated metanephrines 1
  • Additional measurement of plasma methoxytyramine (where available) can help assess malignancy risk 1
• Exception: Screening for pheochromocytoma may be omitted in patients with unequivocal adrenocortical adenomas confirmed on unenhanced CT (HU <10) without signs/symptoms of adrenergic excess 1

Aldosterone Evaluation

• Patients with adrenal incidentalomas and hypertension and/or hypokalemia should be screened for primary aldosteronism 1
• The recommended screening test is the aldosterone-to-renin ratio 1
• If primary aldosteronism is confirmed, adrenal vein sampling is recommended before considering adrenalectomy 1

Androgen Evaluation

• Androgen testing should be performed in cases of:
  • Suspected adrenocortical carcinoma 1
  • Clinical signs of virilization 1
  • Testing should include serum DHEA-S, 17-OH-progesterone, androstenedione, and testosterone 1

Special Considerations

For Suspected Adrenocortical Carcinoma (ACC)

• An extensive steroid hormone workup is recommended, assessing 1:
  • Glucocorticoids (dexamethasone suppression test, 24h urinary free cortisol, basal cortisol, ACTH)
  • Mineralocorticoids (potassium, aldosterone/renin ratio)
  • Sex steroids and precursors (DHEA-S, 17-OH-progesterone, androstenedione, testosterone, estradiol in men and postmenopausal women)
  • 24-hour urine steroid metabolite examination (if available) 1

For Bilateral Adrenal Masses

• Complete hormonal evaluation as outlined above 3
• Additional assessment of adrenal function to rule out adrenal insufficiency 1, 3

Pitfalls and Caveats

• Hormone assays not only help diagnose functional tumors but also provide orientation to the nature of the adrenal mass and can help assess malignancy risk 1
• Abnormal hormone secretions serve as biological markers for patient follow-up 1
• False positive and negative results can occur in hormone testing, requiring careful interpretation 4
• Poor adherence to hormonal evaluation guidelines is common; standardized reporting with specific recommendations for hormonal evaluation significantly improves adherence 5
• Even initially non-functioning adrenal adenomas may develop subclinical hormone secretion during follow-up (approximately 6% in one study), supporting the need for hormonal surveillance 6

Follow-up Hormonal Evaluation

• For patients with non-functioning adrenal adenomas, repeat hormonal evaluation should be performed, typically annually 4
• The frequency and duration of follow-up should be individualized based on prior test results and presence of comorbidities potentially related to hormone excess 4
• For patients with resected adrenocortical carcinoma, regular monitoring of initially elevated steroids every 3 months is recommended 1

By following this comprehensive hormonal evaluation approach, clinicians can effectively identify functional adrenal tumors, assess malignancy risk, and determine appropriate management strategies for patients with adrenal nodules.