How to manage hypercortisolism (elevated cortisol levels)?

From the Guidelines

To manage hypercortisolism, the most effective approach is to use an adrenal steroidogenesis inhibitor, such as osilodrostat or metyrapone, which have the fastest action and are orally available, as recommended by the 2021 consensus on diagnosis and management of Cushing's disease 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 cases where rapid normalization of cortisol is necessary, osilodrostat and metyrapone are preferred due to their fast action.
• For mild disease with residual tumor, pasireotide or cabergoline may be considered, but cabergoline should be avoided in patients with a history of bipolar or impulse control disorder.
• Mifepristone can be used cautiously, but its use requires careful monitoring and consideration of drug-drug interactions.
• In pregnant women or those desiring pregnancy, cabergoline or metyrapone may be considered, although no medications are approved for use in pregnancy. The choice of medication should also take into account factors such as cost, estimated therapy duration, and the presence of concomitant comorbidities like type 2 diabetes and hypertension. It is essential to prioritize the patient's health and well-being, minimizing the risk of morbidity, mortality, and reducing the impact on quality of life. Lifestyle modifications, including regular exercise, adequate sleep, stress management, and a balanced diet, can also help support the body's natural cortisol rhythm, but these should be used in conjunction with medical therapy under the guidance of a healthcare provider. Ultimately, the management of hypercortisolism requires a personalized approach, taking into account the individual patient's needs and circumstances, and should be guided by the most recent and highest-quality evidence, such as the 2021 consensus on diagnosis and management of Cushing's disease 1.

From the FDA Drug Label

PRECAUTIONS General Precautions Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. The answer to managing hypercortisolism is not directly addressed in the provided drug label. Hypercortisolism management is not explicitly mentioned, and the label primarily discusses precautions for corticosteroid use.

• The label does discuss the potential for drug-induced secondary adrenocortical insufficiency, but this is not the same as managing hypercortisolism.
• It does not provide guidance on how to manage elevated cortisol levels. 2

From the Research

Managing Hypercortisolism

To manage hypercortisolism, or elevated cortisol levels, several strategies can be employed, including:

• Yoga: Studies have shown that yoga can reduce cortisol levels and have an antidepressant effect 3
• Meditation: Meditation interventions have been found to efficiently reduce cortisol levels, particularly in at-risk samples 4
• Ashwagandha: Ashwagandha root has been used to treat non-classical adrenal hyperplasia and has been shown to decrease serum cortisol levels 5
• Stress management interventions: A systematic review and meta-analysis found that stress management interventions, including mind body therapies, mindfulness, relaxation, and talking therapies, can positively influence cortisol levels 6
• Lifestyle modifications: Healthy lifestyle changes, such as dietary advice combined with aerobic exercise or high-intensity interval training, can improve cortisol levels and reduce hepatic steatosis in patients with MASLD 7

Effective Interventions

Some interventions have been found to be more effective than others in reducing cortisol levels, including:

• Mindfulness and meditation: These interventions have been shown to have a medium positive effect size in reducing cortisol levels 6
• Relaxation: Relaxation interventions have also been found to be effective in reducing cortisol levels 6
• High-intensity interval training (HIIT): HIIT combined with dietary advice has been shown to significantly decrease cortisol levels 7
• Aerobic exercise: Aerobic exercise combined with dietary advice has been found to reduce hepatic steatosis and decrease cortisol levels 7

Key Findings

Key findings from the studies include:

• Cortisol levels can be reduced through various interventions, including yoga, meditation, and stress management interventions 3, 4, 6
• Ashwagandha root can be used to treat non-classical adrenal hyperplasia and reduce serum cortisol levels 5
• Lifestyle modifications, such as dietary advice combined with exercise, can improve cortisol levels and reduce hepatic steatosis in patients with MASLD 7
• The effectiveness of interventions can depend on the population being studied, with at-risk samples showing larger effects of meditation interventions 4