What is the diagnosis and treatment for a patient with elevated serum cortisol level, low Adrenocorticotropic hormone (ACTH) level, and an adrenal tumor?

Diagnosis and Management of Adrenal Tumor with Elevated Cortisol and Low ACTH

The clinical picture of elevated serum cortisol with low ACTH levels in the presence of an adrenal tumor is diagnostic of ACTH-independent Cushing syndrome, most likely due to a cortisol-producing adrenal adenoma. 1

Diagnostic Confirmation

• Biochemical profile:

  • Elevated serum cortisol
  • Suppressed ACTH levels
  • This pattern indicates autonomous cortisol production from the adrenal gland, bypassing normal pituitary regulation 1

• Additional confirmatory tests:

  • 24-hour urinary free cortisol (elevated in Cushing syndrome)
  • 1mg overnight dexamethasone suppression test (failure to suppress cortisol below 1.8 μg/dL) 1
  • Late-night salivary cortisol (elevated in Cushing syndrome)

• Imaging:

  • Non-contrast CT scan of adrenal glands (first-line imaging) 1
  • If Hounsfield units <10, likely benign adenoma
  • If Hounsfield units >10, proceed with contrast-enhanced CT with washout protocol or chemical-shift MRI 1
  • Assess for:
    • Size (>4cm raises suspicion for malignancy)
    • Homogeneity (heterogeneous appearance suggests malignancy)
    • Margins (irregular margins suggest malignancy)
    • Local invasion (suggests malignancy) 1

Differential Diagnosis

1. Cortisol-producing adrenal adenoma (most likely) 1, 2

   • Benign tumor with autonomous cortisol production
   • May present with subtle or overt Cushing syndrome

2. Adrenocortical carcinoma 1, 3

   • Consider if tumor >4cm, irregular margins, heterogeneous appearance
   • Often produces multiple hormones (cortisol and androgens)
   • More aggressive clinical course

3. Bilateral adrenal hyperplasia 1

   • Less likely given presence of a discrete tumor

Treatment Approach

1. Surgical Management:

   • Laparoscopic adrenalectomy is the treatment of choice for cortisol-producing adrenal adenomas 1
   • Open adrenalectomy should be considered if:
     • Tumor size >5-6cm
     • Imaging suggests malignancy (irregular margins, local invasion)
     • Concern for adrenocortical carcinoma 1

2. Perioperative Management:

   • Critical: Perioperative glucocorticoid coverage is mandatory 2, 4
     • The contralateral adrenal gland is typically suppressed due to chronic cortisol excess
     • Failure to provide glucocorticoid coverage can lead to life-threatening adrenal crisis 5, 2
   • Typical regimen: Hydrocortisone 100mg IV at induction, followed by stress-dose coverage

3. Postoperative Management:

   • Continue glucocorticoid replacement (typically hydrocortisone 15-20mg daily in divided doses) 6
   • Gradually taper dose over 6-12 months as HPA axis recovers
   • Monitor for signs of adrenal insufficiency during tapering
   • Regular assessment of morning cortisol levels to evaluate recovery of HPA axis 6, 2

Follow-up

• Monitor for resolution of hypercortisolism symptoms
• Regular assessment of cortisol levels
• For patients with adrenocortical carcinoma: more intensive surveillance with imaging every 3-6 months 1
• Monitor for improvement in metabolic parameters:
  • Blood pressure
  • Glucose tolerance
  • Potassium levels 2, 4

Common Pitfalls to Avoid

1. Failure to recognize subclinical Cushing syndrome - Even without overt cushingoid features, autonomous cortisol production can suppress the contralateral adrenal gland 2

2. Omitting perioperative glucocorticoid coverage - Can lead to life-threatening adrenal crisis 5

3. Premature discontinuation of postoperative glucocorticoid replacement - HPA axis recovery may take 6-12 months or longer 6

4. Missing co-secretion of other hormones - Some adrenal tumors can co-secrete aldosterone or catecholamines 7, 4

5. Inadequate radiological assessment - Failure to distinguish between benign adenoma and adrenocortical carcinoma 1

By following this approach, patients with cortisol-producing adrenal tumors can be effectively diagnosed and managed to minimize morbidity and mortality associated with both the disease and its treatment.