What methods can reduce endogenous cortisol production?

From the Guidelines

To reduce endogenous cortisol production, the most effective method is using adrenal steroidogenesis inhibitors such as osilodrostat and metyrapone, which have the fastest action and are orally available, as recommended by the most recent and highest quality study 1.

Methods to Reduce Cortisol Production

The goal of reducing cortisol production is crucial in managing conditions like Cushing's disease. Several methods can be employed to achieve this, including:

• Medical therapies: Adrenal steroidogenesis inhibitors like osilodrostat and metyrapone are highly effective in reducing cortisol levels, either alone or in combination 1.
• Lifestyle modifications: While not directly addressed in the provided evidence, lifestyle changes such as regular physical activity, stress management techniques, adequate sleep, and dietary changes can also play a role in regulating cortisol levels.

Medical Therapies

Medical therapies are a primary approach in reducing cortisol production. The choice of medication depends on several factors including the need for rapid normalization of cortisol, the presence of residual tumor, and potential for tumor shrinkage.

• Osilodrostat and metyrapone are recommended for rapid normalization of cortisol due to their fast action and oral availability 1.
• Pasireotide or cabergoline may be considered in mild disease with potential for tumor shrinkage, but cabergoline should be avoided in patients with a history of bipolar or impulse control disorder 1.
• Mifepristone can be used cautiously, especially when an expert pituitary endocrinologist is not available to monitor treatment response, and considering its potential drug-drug interactions 1.

Considerations

When selecting a medical therapy, several factors should be considered:

• The need for rapid normalization of cortisol levels
• The presence of residual tumor and potential for tumor shrinkage
• History of bipolar or impulse control disorder
• Pregnancy or desire for pregnancy
• Drug intolerance or side effects
• Concomitant comorbidities such as type 2 diabetes mellitus and hypertension
• Cost and estimated therapy duration, especially if definitive treatment is planned or while awaiting effects of radiotherapy 1.

Conclusion is not allowed, so the answer just ends here.

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.

The method that can reduce endogenous cortisol production is:

• Inhibiting the 11-beta-hydroxylation reaction in the adrenal cortex, such as with metyrapone 2.
• Etomidate may also suppress endogenous cortisol and aldosterone production 3.

From the Research

Methods to Reduce Endogenous Cortisol Production

Several methods can be used to reduce endogenous cortisol production, including:

• Adrenal-blocking agents, such as ketoconazole and metyrapone, which suppress adrenal cortisol production via inhibition of steroidogenic enzymes 4, 5, 6, 7
• Neuromodulatory drugs, such as cabergoline and pasireotide, which target the corticotropic adenoma and can be used in combination with adrenal-blocking agents 4, 5
• Glucocorticoid receptor antagonists, such as mifepristone, which block cortisol action at its receptor 4
• Steroidogenesis enzyme inhibitors, such as osilodrostat, which inhibit various enzymes along the cortisol biosynthetic pathway 7
• Etomidate, which suppresses cortisol production primarily by inhibiting 11β-hydroxylase and can be given parenterally 6, 7, 8

Specific Drugs and Their Effects

Some specific drugs that can reduce endogenous cortisol production include:

• Ketoconazole, which can normalize cortisol levels in about 50-90% of patients with Cushing's disease 5, 6, 8
• Metyrapone, which can reduce cortisol levels but has several side effects and limited efficacy 4, 5, 6
• Etomidate, which can rapidly reduce cortisol levels but has sedative-hypnotic actions that limit its use 6, 7, 8
• Cabergoline, which can normalize cortisol levels in about one-third of patients with Cushing's disease 4
• Pasireotide, which can normalize cortisol levels in about 25% of patients with Cushing's disease but can cause worsening of glucose tolerance 4