How to lower elevated cortisol levels?

From the Guidelines

To lower elevated cortisol levels, the most effective approach is to use an adrenal steroidogenesis inhibitor, such as osilodrostat or metyrapone, which can rapidly normalize cortisol levels, especially in severe cases. This recommendation is based on the most recent and highest quality study available, which suggests that these medications have the fastest action and are orally available 1. For patients with severe disease, rapid normalization of cortisol is the most important goal, and osilodrostat and metyrapone can achieve this within hours, while ketoconazole works within a few days 1.

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. In mild disease, pasireotide or cabergoline may be considered, especially if there is a potential for tumor shrinkage 1. However, cabergoline should be used with caution in patients with a history of bipolar or impulse control disorder 1.

In addition to medical therapy, lifestyle modifications can also help reduce cortisol levels. These include stress management techniques like deep breathing, meditation, and regular physical activity, as well as maintaining a balanced diet and getting adequate sleep. Supplements like ashwagandha, phosphatidylserine, and magnesium may also be helpful in reducing cortisol levels.

It is essential to note that the management of elevated cortisol levels should be individualized, taking into account the severity of the disease, the presence of comorbidities, and the potential for drug interactions. Therefore, it is crucial to work with a healthcare provider to determine the best course of treatment. The goal of treatment is to reduce cortisol levels to normal, which can help alleviate symptoms and improve quality of life.

Some key points to consider when managing elevated cortisol levels include:

• The need for rapid normalization of cortisol in severe cases
• The potential for tumor shrinkage with certain medications
• The importance of considering comorbidities and drug interactions
• The role of lifestyle modifications in reducing cortisol levels
• The need for individualized treatment plans.

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.

To lower elevated cortisol levels, Metyrapone can be used as it inhibits the production of cortisol and corticosterone by blocking the 11-beta-hydroxylation reaction in the adrenal cortex 2.

• The reduction of cortisol production is a direct result of metyrapone's mechanism of action.
• Metyrapone may also suppress biosynthesis of aldosterone, resulting in a mild natriuresis.
• It is essential to note that metyrapone is used as a diagnostic test, with urinary 17-OHCS measured as an index of pituitary ACTH responsiveness 2.

From the Research

Lowering Cortisol Levels

To lower elevated cortisol levels, several medical therapies can be employed. These therapies aim to inhibit the production of cortisol in the adrenal glands.

• Adrenally directed medical therapies, such as ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate, can be used to treat Cushing's syndrome, a condition characterized by excess cortisol secretion 3.
• Metyrapone, an inhibitor of 11β-hydroxylase, has been shown to decrease cortisol secretion in patients with Cushing's syndrome, with a median dose of 1000 mg for 9 months resulting in sustained urinary-free cortisol normalization up to 12 and 24 months in some patients 4.
• Etomidate, another inhibitor of 11β-hydroxylase, can be used to suppress cortisol production, but its sedative-hypnotic actions limit its use as an acute management option for Cushing's syndrome 5.
• Combination therapy with mitotane, metyrapone, and ketoconazole has been shown to be effective in severe ACTH-dependent Cushing's syndrome, avoiding the need for emergency bilateral adrenalectomy 6.
• Osilodrostat, a new drug, has been approved by the US Food and Drug Administration for the treatment of Cushing's disease and may be used to lower cortisol levels 5, 3, 7.

Treatment Options

The choice of treatment depends on the severity of the condition, the presence of comorbidities, and the patient's response to therapy.

• Adrenal steroidogenesis inhibitors, such as etomidate, ketoconazole, and metyrapone, are commonly used as first-line treatment for severe hypercortisolemia due to their rapid action and good efficacy and safety profile 7.
• Glucocorticoid receptor antagonists, such as mifepristone, may also be used, but their use is limited due to difficulties in monitoring efficacy and safety 7.
• Bilateral adrenalectomy may be indicated as a life-saving measure when medical therapies fail, are unavailable, or are contraindicated 7.