Latest Protocol for Workup of Adrenal Adenoma Cushing's Syndrome
The recommended protocol for workup of adrenal adenoma Cushing's syndrome involves a comprehensive hormonal evaluation with a 1 mg overnight dexamethasone suppression test as the initial screening test, followed by confirmatory testing and imaging studies to characterize the adrenal mass. 1, 2
Initial Screening and Diagnosis
- All patients with suspected adrenal adenoma Cushing's syndrome should undergo a 1 mg overnight dexamethasone suppression test, with serum cortisol measured at 8 AM the next morning after administering 1 mg dexamethasone at 11 PM 1
- Interpretation of dexamethasone suppression test results 1:
- Serum cortisol ≤50 nmol/L (1.8 μg/dL): excludes autonomous cortisol secretion
- Serum cortisol 51-138 nmol/L (1.9-5.0 μg/dL): possible autonomous cortisol secretion
- Serum cortisol >138 nmol/L (>5.0 μg/dL): evidence of autonomous cortisol secretion
- Plasma ACTH levels should be measured to differentiate between ACTH-dependent and ACTH-independent Cushing's syndrome; low or undetectable ACTH levels suggest an adrenal source 2, 3
- Additional confirmatory tests for cortisol excess may include 24-hour urinary free cortisol and late-night salivary cortisol 3
Imaging Evaluation
- Non-contrast CT is the first-line imaging modality to characterize adrenal masses 1, 4
- Benign features on imaging include 1, 4:
- Homogeneous, well-circumscribed appearance
- <10 Hounsfield Units (HU) on non-contrast CT
- Size <4 cm
- For indeterminate masses on non-contrast CT, second-line imaging should be performed 1:
- Washout CT protocol
- Chemical-shift MRI
Additional Hormonal Evaluation
- Even when cortisol excess is confirmed, comprehensive hormonal evaluation should include 1, 2:
- Aldosterone-to-renin ratio (particularly in patients with hypertension and/or hypokalemia)
- Plasma free metanephrines or 24-hour urinary metanephrines (especially for masses >10 HU on non-contrast CT or with symptoms of catecholamine excess)
- Serum androgen testing (DHEAS, testosterone) if there are signs of virilization or if adrenocortical carcinoma is suspected
Management Decision Algorithm
- Unilateral cortisol-secreting adrenal masses with clinically apparent Cushing's syndrome should undergo unilateral adrenalectomy 5
- For mild autonomous cortisol secretion (MACS, previously called subclinical Cushing's syndrome) 5:
- Consider adrenalectomy for younger patients with progressive metabolic comorbidities attributable to cortisol excess
- For patients not managed surgically, perform annual clinical screening for new or worsening associated comorbidities
- Minimally invasive surgery (laparoscopic/robotic adrenalectomy) should be performed when feasible 5
- For suspicious masses (>4 cm, inhomogeneous appearance, >20 HU, or growth >5 mm/year), surgical intervention should be considered after repeating functional workup 1
Perioperative Considerations
- Preoperative management must include treatment of comorbid conditions such as diabetes and hypertension 5
- Intraoperative planning should include special attention to prophylactic antibiotics 5
- Hydrocortisone supplementation during surgery and postoperatively is necessary to prevent adrenal crisis 6
Follow-up Protocol
- After resection of cortisol-secreting adenomas, patients should be monitored for 5:
- Resolution of hypercortisolism
- Improvement in comorbid conditions
- Potential recurrence (estimated at around 10% in the original adrenal gland and up to 30% in the contralateral gland)
- Lifelong monitoring is necessary due to the significant risk of recurrence 5
Important Pitfalls to Avoid
- Do not rely solely on radiological appearance to predict hormone secretion status 2
- Do not perform adrenal mass biopsy without excluding pheochromocytoma, as this can trigger life-threatening hypertensive crisis 2
- Do not skip hormone testing even in apparently non-functioning tumors, as subtle hormone production can impact surgical management and perioperative care 2
- Avoid unnecessary repeated imaging for small adrenal masses with benign characteristics 4