What's the next step in managing a patient with hypercortisolism (elevated cortisol levels), inappropriately suppressed Adrenocorticotropic hormone (ACTH), hypogonadism (low Follicle-stimulating hormone (FSH)), and a partially empty sella with an intermediate gray nodule?

Management of Hypercortisolism with Low ACTH, Hypogonadism, and Partially Empty Sella

For a patient with hypercortisolism, suppressed ACTH, hypogonadism (low FSH), and a partially empty sella with an intermediate gray nodule, surgical resection of the adrenal gland is the recommended next step in management. 1

Diagnostic Interpretation

The clinical picture strongly suggests ACTH-independent Cushing syndrome originating from the adrenal gland:

• Elevated cortisol with suppressed ACTH indicates adrenal (not pituitary) source of hypercortisolism 1
• Hypogonadism with low FSH suggests secondary endocrine dysfunction from cortisol excess 1
• Partially empty sella with nodule is likely an incidental finding or result of previous pituitary damage 1, 2

Management Algorithm

1. Confirm adrenal source of hypercortisolism

   • Low/suppressed ACTH with elevated cortisol confirms ACTH-independent Cushing syndrome 1
   • This pattern indicates autonomous cortisol production from the adrenal gland rather than pituitary or ectopic ACTH production 1

2. Imaging of adrenal glands

   • CT or MRI of adrenal glands to identify adrenal adenoma or carcinoma 1
   • Evaluate for features suggesting malignancy: size >5cm, irregular margins, heterogeneous appearance, local invasion 1

3. Surgical management

   • For benign adrenal adenoma: laparoscopic adrenalectomy 1
   • For suspected malignant adrenal tumor: open adrenalectomy with lymph node removal 1
   • Postoperative corticosteroid supplementation will be required until HPA axis recovery 1

4. Follow-up management

   • Monitor for resolution of hypercortisolism 1
   • Assess pituitary function to determine if hypogonadism resolves after cortisol normalization 1
   • Further evaluation of partially empty sella if endocrine abnormalities persist 1

Important Considerations

• The combination of elevated cortisol with suppressed ACTH is diagnostic of adrenal Cushing syndrome, not pituitary Cushing disease 1
• Hypogonadism (low FSH) may be secondary to hypercortisolism and could improve after treatment of the primary condition 1
• The partially empty sella with nodule requires follow-up imaging after cortisol normalization to determine clinical significance 1
• Bilateral inferior petrosal sinus sampling is not indicated when ACTH is suppressed, as this confirms an adrenal source 1

Potential Pitfalls

• Mistaking this for Cushing disease (pituitary source) would lead to inappropriate pituitary surgery 3
• Failure to recognize adrenal source could delay appropriate treatment 1
• Inadequate preoperative imaging could miss adrenal malignancy requiring more aggressive surgical approach 1
• Postoperative adrenal insufficiency is expected and requires glucocorticoid replacement until HPA axis recovery 1

Medical Management Options

If surgery is contraindicated:

• Adrenostatic agents (ketoconazole 400-1200 mg/day) can be used to control hypercortisolism 1
• Mitotane is an alternative medical therapy for cortisol excess 1
• Treatment of comorbidities (hypertension, hyperglycemia, hypokalemia) may be required 1