What is the treatment for elevated morning cortisol levels with normal Adrenocorticotropic Hormone (ACTH) levels?

From the Guidelines

The treatment for a morning cortisol level of 21.1 μg/dL with a normal ACTH typically involves addressing mild hypercortisolism, and initial management should focus on identifying and treating the underlying cause, which may be exogenous steroid use, adrenal adenoma, or stress-related elevation.

Key Considerations

• If an adrenal source is confirmed through additional testing (such as dexamethasone suppression test or imaging), medications like ketoconazole (starting at 200mg twice daily) or metyrapone (250-500mg every 6 hours) may be prescribed to reduce cortisol production, as suggested by 1.
• Lifestyle modifications are also important, including stress reduction techniques, regular exercise, and a balanced diet low in simple carbohydrates.
• Blood pressure and blood glucose should be monitored regularly, as hypercortisolism can affect both, and this is crucial for preventing long-term complications such as cardiovascular disease and diabetes, as implied by 1.
• The normal ACTH level suggests this is not pituitary-driven Cushing's disease but rather may be adrenal in origin or a non-pathological elevation.

Treatment Approach

• Follow-up testing is essential to confirm persistent hypercortisolism before initiating specific treatments, as single elevated morning cortisol readings can occur due to acute stress, sleep disturbances, or other temporary factors.
• For patients with severe disease, rapid normalization of cortisol is the most important goal, and medications like osilodrostat and metyrapone can achieve this within hours, as stated in 1.
• In cases where hypercortisolism is very severe and not responsive to optimized medical therapy, including combinations, bilateral adrenalectomy (BLA) should be considered to avoid worsening outcomes, as recommended by 1.

Monitoring and Adjustments

• Regular monitoring of cortisol levels, blood pressure, and blood glucose is necessary to adjust the treatment plan as needed.
• The choice of medication should be guided by factors such as the need for rapid normalization of cortisol, potential for tumor shrinkage, history of bipolar or impulse control disorder, and presence of comorbidities like type 2 diabetes and hypertension, as discussed in 1.

From the Research

Treatment for Morning Cortisol of 21.1 with Normal ACTH

• The provided studies do not directly address the treatment for a morning cortisol level of 21.1 with a normal ACTH level 2, 3, 4, 5, 6.
• However, the studies discuss the treatment of Cushing's syndrome, which is characterized by excess cortisol production.
• The treatment options mentioned in the studies include adrenal steroidogenesis inhibitors such as etomidate, ketoconazole, and metyrapone, which can help lower cortisol levels 2, 3, 4, 5, 6.
• Metyrapone is shown to be effective in controlling hypercortisolemia in patients with Cushing's syndrome, with significant improvements in biochemical parameters such as serum cortisol and 24-hour urinary free cortisol 4, 6.
• Combination therapy with mitotane, metyrapone, and ketoconazole is also shown to be effective in severe ACTH-dependent Cushing's syndrome, avoiding the need for emergency bilateral adrenalectomy 5.

Medications Used to Treat Cushing's Syndrome

• Etomidate: an adrenal steroidogenesis inhibitor that suppresses cortisol production primarily by inhibiting 11β-hydroxylase 2, 3.
• Ketoconazole: an antifungal agent that inhibits various enzymes along the cortisol biosynthetic pathway 2, 3, 5.
• Metyrapone: a steroidogenesis inhibitor that decreases serum cortisol levels and increases serum 11-desoxycortisol levels 4, 5, 6.
• Mitotane: a medication that is highly effective in the long-term management of Cushing's syndrome, but has a slow onset of action 5.
• Osilodrostat: a new drug that is a potential candidate for the treatment of Cushing's disease 2, 3.