Ketoconazole for Adrenal Incidentaloma

This trial aims to understand how cortisol levels differ between people with mild autonomous cortisol secretion (MACS), a condition that causes excess cortisol production, and healthy individuals. Researchers are testing whether ketoconazole, an antifungal medication that can also lower cortisol levels, can effectively reduce cortisol in people with MACS. The trial includes participants with MACS who have conditions like high blood pressure or diabetes, along with healthy volunteers for comparison. Participants with MACS will stay in the hospital for two nights for monitoring and treatment, while healthy volunteers will stay for one night. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to contribute to groundbreaking research.

Yes, you may need to stop certain medications before joining the trial. Specifically, you cannot take medications that affect cortisol production or action, certain heart medications, or drugs that interact with ketoconazole within two weeks before the trial. You also need to pause some acid-reducing medications for a short time.

Research has shown that ketoconazole is generally safe for most people. This medication often lowers cortisol levels and has helped patients with conditions like Mild Autonomous Cortisol Secretion (MACS), where the body produces too much cortisol.

In studies, most participants did not experience serious side effects from ketoconazole. Common issues might include nausea or changes in liver function, but these are usually mild. Ketoconazole has been used for a long time and has FDA approval for other conditions, which gives researchers confidence in its safety for this use.

Unlike the standard treatments for adrenal incidentaloma, which can include surgery or medications like metyrapone and mitotane, ketoconazole works by inhibiting cortisol synthesis, offering a potentially less invasive option. Researchers are particularly excited because ketoconazole could provide a more targeted approach to managing mild autonomous cortisol secretion (MACS), potentially reducing the risk of overtreatment associated with surgical interventions. Additionally, its ability to quickly adjust cortisol levels gives it an edge in managing this condition more dynamically compared to some existing therapies.

Research has shown that ketoconazole can effectively lower cortisol levels. One study brought cortisol levels in urine (a measure of cortisol in the body) back to normal in 79% of patients. Another study found that ketoconazole helped 85% of patients achieve normal or lower cortisol levels within 5 to 150 days of treatment. In this trial, participants with mild autonomous cortisol secretion (MACS) will receive a single dose of ketoconazole to assess its impact on cortisol levels. By lowering cortisol levels, ketoconazole could potentially reduce symptoms like high blood pressure, diabetes, and weight gain associated with MACS.⁶⁷⁸⁹¹⁰