What are the primary goals for cortisol and Adrenocorticotropic Hormone (ACTH) levels after macroadenoma resection?

From the Guidelines

The primary goals for cortisol and ACTH levels after macroadenoma resection are to achieve normal physiological levels while avoiding both hypocortisolism and persistent hypercortisolism, with morning cortisol levels between 5-25 μg/dL and ACTH levels between 10-60 pg/mL. After surgery, patients with Cushing's disease (ACTH-secreting adenomas) should have cortisol levels below 2 μg/dL in the immediate post-operative period, indicating complete tumor removal 1. These patients typically require glucocorticoid replacement (hydrocortisone 15-20 mg daily in divided doses) until their hypothalamic-pituitary-adrenal (HPA) axis recovers, which may take 6-18 months.

Key Considerations

• For non-functioning macroadenomas, the concern is hypocortisolism due to surgical manipulation of the normal pituitary, and patients need close monitoring of morning cortisol levels (target >10 μg/dL without replacement)
• Patients may require temporary hydrocortisone replacement if levels are low, and should be educated about adrenal insufficiency symptoms and carry emergency medical identification if on replacement therapy
• Regular follow-up testing every 3-6 months is essential to adjust replacement doses or discontinue therapy when the HPA axis recovers, as noted in recent guidelines on the management of Cushing's disease 1.

Monitoring and Management

• Morning cortisol measurements and ACTH stimulation tests are used to monitor recovery of the HPA axis
• The risk of adrenal insufficiency (AI) with overtreatment, and inappropriate GC over-replacement if blockade is incomplete, should be considered when treating patients with adrenal steroidogenesis inhibitors 1.
• Potential adverse events (AEs) related to drug-drug interactions are a key factor in treatment selection and use, and should be carefully managed to minimize risks to patients.

From the Research

Primary Goals for Cortisol and ACTH Levels

The primary goals for cortisol and Adrenocorticotropic Hormone (ACTH) levels after macroadenoma resection are:

• To achieve normal cortisol levels, indicating a successful treatment of Cushing's disease 2, 3, 4
• To restore normal ACTH levels and response to stimulation tests, such as the corticotropin-releasing hormone (CRH) test 2, 4
• To prevent long-term hormonal deficiencies, such as adrenal insufficiency 5, 6

Factors Affecting Outcome

Several factors can affect the outcome of macroadenoma resection, including:

• Tumor size and invasiveness: larger and more invasive tumors are associated with lower remission rates and higher recurrence rates 2, 3
• Baseline ACTH levels: higher baseline ACTH levels are associated with lower remission rates and higher recurrence rates 2, 4
• Response to stimulation tests: impaired response to CRH and high-dose dexamethasone suppression tests are associated with lower remission rates and higher recurrence rates 2, 4

Management Strategies

Management strategies for patients with macroadenomas include:

• Surgery: transsphenoidal adenomectomy (TSA) is the primary treatment for macroadenomas, with the goal of achieving complete tumor removal 2, 3, 6
• Radiotherapy: may be used as an adjunctive treatment for patients with residual or recurrent disease 2, 3
• Medical therapy: may be used to control cortisol levels in patients with residual or recurrent disease, or to prevent adrenal insufficiency 2, 5, 6