From the Guidelines
To effectively lower cortisol levels, the most recent and highest quality study recommends using an adrenal steroidogenesis inhibitor, such as osilodrostat or metyrapone, which have the fastest action and are orally available. When selecting a medical therapy, several factors should be considered, including the need for rapid normalization of cortisol, the presence of residual tumor, and the potential for tumor shrinkage 1. For patients with severe disease, rapid normalization of cortisol is the most important goal, and osilodrostat and metyrapone have been shown to be effective in achieving this goal, with response typically seen within hours 1.
Some key points to consider when using these medications include:
- The need for regular monitoring of treatment efficacy, including measures of cortisol and patient symptoms and comorbidities 1
- The potential for drug-drug interactions and overlapping toxicities, particularly QTc prolongation 1
- The importance of counseling patients that cortisol cannot be used to monitor treatment response or AI when using certain medications, such as mifepristone 1
- The need to consider cost and estimated therapy duration, especially if definitive treatment is planned or while awaiting effects of radiotherapy 1
In terms of specific medications, osilodrostat has been shown to have the highest efficacy based on data from several prospective clinical trials, followed by metyrapone 1. Metyrapone has been shown to be effective in normalizing UFC levels in 71% of patients, with a median dose of 2127.5 mg/d and a mean follow-up of 8.7 months 1.
Overall, the goal of treatment should be to rapidly normalize cortisol levels, while also considering the potential risks and benefits of each medication, as well as the individual patient's needs and circumstances. By using an adrenal steroidogenesis inhibitor, such as osilodrostat or metyrapone, and carefully monitoring treatment efficacy and potential side effects, it is possible to effectively lower cortisol levels and improve patient outcomes.
From the FDA Drug Label
The pharmacological effect of Metopirone is to reduce cortisol and corticosterone production by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex.
Metyrapone can effectively lower cortisol levels by inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex, which reduces cortisol and corticosterone production. This is the mechanism of action of metyrapone. 2
From the Research
Effective Methods to Lower Cortisol Levels
- Medical therapy, including adrenal-blocking agents, neuromodulatory drugs, and glucocorticoid receptor antagonists, can be used to treat hypercortisolism 3, 4
- Stress management interventions, such as mindfulness, meditation, and relaxation, have been shown to positively influence cortisol levels 5
- Yoga-based lifestyle interventions can reduce stress and inflammation, including cortisol levels, in as little as 10 days 6
- Pharmacological treatments, including steroidogenesis enzyme inhibitors like ketoconazole, metyrapone, and etomidate, can be used to lower cortisol levels in patients with Cushing's syndrome 3, 7, 4
Pharmacological Treatments
- Ketoconazole is a commonly used adrenal-blocking agent that can suppress adrenal cortisol production 3, 7, 4
- Etomidate is a steroidogenesis enzyme inhibitor that can be used to rapidly reverse cortisol excess in patients with acute complications of hypercortisolism 3, 7
- Metyrapone is another adrenal-blocking agent that can be used to treat hypercortisolism, but it can have side effects like increased androgen and mineralocorticoid production 3, 4
Non-Pharmacological Interventions
- Mindfulness and meditation interventions have been shown to be effective in changing cortisol levels 5
- Relaxation interventions, such as yoga and deep breathing, can also help reduce cortisol levels 5
- Yoga-based lifestyle interventions can reduce stress and inflammation, including cortisol levels, in as little as 10 days 6