What is the management approach for a patient with hypercortisolism (high cortisol) and low Adrenocorticotropic hormone (ACTH) levels?

Management of High Cortisol with Low ACTH

The management of hypercortisolism with low ACTH levels requires surgical removal of the adrenal tumor as the first-line treatment, as this condition strongly indicates ACTH-independent Cushing's syndrome from an adrenal source. 1

Diagnostic Approach

When faced with high cortisol and low ACTH, the following diagnostic algorithm should be implemented:

1. Confirm hypercortisolism with at least two of these tests:

   • 24-hour urinary free cortisol (UFC) measurements (collect for 3 days)
   • Low-dose dexamethasone suppression test (LDDST)
   • Late-night salivary cortisol test 1

2. Confirm ACTH-independence:

   • Morning ACTH levels <5 ng/L (<1.1 pmol/L) with confirmed hypercortisolism indicates adrenal source 1
   • This pattern differentiates from pituitary or ectopic ACTH-dependent Cushing's syndrome

3. Localize the adrenal source:

   • Adrenal CT scan to identify adrenal tumor(s) 1
   • For bilateral adrenal nodules, adrenal vein sampling may be necessary to determine the source of cortisol production 2

Management Protocol

For Unilateral Adrenal Adenoma

1. Surgical intervention:

   • Laparoscopic adrenalectomy of the affected gland is the treatment of choice 1
   • Postoperative corticosteroid supplementation is required until recovery of the hypothalamic-pituitary-adrenal (HPA) axis 1

2. Perioperative management:

   • Prepare for potential adrenal crisis post-surgery
   • Administer stress-dose corticosteroids during and after surgery 1
   • Monitor for symptoms of adrenal insufficiency

3. Post-surgical follow-up:

   • Hydrocortisone replacement (typically 15-20 mg daily in divided doses) 1
   • Taper stress-dose corticosteroids to maintenance doses over 5-7 days 1
   • Test for HPA axis recovery after 3 months of maintenance therapy 1

For Bilateral Adrenal Disease

1. If asymmetric cortisol production is confirmed by adrenal vein sampling:

   • Unilateral adrenalectomy of the most active side 1
   • Postoperative corticosteroid supplementation

2. If symmetric cortisol production:

   • Medical management is indicated 1
   • Consider adrenostatic agents like ketoconazole (400-1200 mg/day) or mitotane 1

For Adrenal Carcinoma (if suspected)

1. Indicators of malignancy:

   • Tumor size >5 cm
   • Irregular morphology, inhomogeneous appearance
   • Local invasion or metastases 1

2. Treatment:

   • Open adrenalectomy rather than laparoscopic approach 1
   • Consider adjuvant therapy based on staging

Patient Education and Long-term Management

1. Steroid education:

   • Stress dosing instructions for illness or surgery
   • Emergency injectable corticosteroids
   • Medical alert bracelet for adrenal insufficiency 1

2. Follow-up monitoring:

   • Regular assessment of cortisol levels
   • Monitor for recurrence of hypercortisolism
   • Endocrine consultation prior to any surgical procedures 1

Common Pitfalls to Avoid

1. Failure to recognize adrenal insufficiency post-surgery, which can be life-threatening

   • Symptoms include hypotension, hyponatremia, hyperkalemia, and fatigue 1

2. Inadequate perioperative steroid coverage

   • Even with unilateral disease, the contralateral adrenal may be suppressed 3

3. Misdiagnosis of bilateral disease

   • Adrenal vein sampling may be necessary when imaging shows bilateral nodules 2

4. Overlooking subclinical Cushing's syndrome

   • Some patients may have autonomous cortisol production without full clinical manifestations 4

By following this structured approach, the management of hypercortisolism with low ACTH can be optimized to improve patient outcomes and reduce complications related to both the disease and its treatment.