From the Guidelines
High cortisol levels, particularly in the morning, can be a normal part of the body's circadian rhythm, but consistently elevated levels may indicate an underlying issue such as Cushing's syndrome, which requires medical attention. Cortisol typically peaks in the morning to help the body wake up and feel alert, as part of its natural stress hormone regulation system 1. If concerns about consistently elevated morning cortisol levels persist, lifestyle modifications such as regular sleep schedules, stress management techniques, regular exercise, and a balanced diet low in sugar and processed foods can be beneficial 1. It's also important to avoid excessive caffeine, especially in the morning when cortisol is naturally high.
Key Considerations
- If symptoms like fatigue, weight gain, mood changes, or sleep disturbances persist despite lifestyle changes, consulting a healthcare provider for a 24-hour cortisol test or salivary cortisol measurements may be necessary to properly assess cortisol levels throughout the day 1.
- Medical conditions like Cushing's syndrome, though rare, can cause pathologically high cortisol levels and require medical treatment, including potential medication adjustments or surgical interventions 1.
- The goal in managing cortisol levels is not to eliminate the natural morning peak but to ensure that cortisol levels are within healthy ranges to prevent potential morbidity and mortality associated with chronically elevated cortisol, such as increased risk of cardiovascular events and metabolic syndrome 1.
Management Approach
- For patients with Cushing's syndrome, regular monitoring of treatment efficacy, including measures of cortisol and patient symptoms, is crucial 1.
- Change in treatment should be considered if cortisol levels are persistently elevated after 2–3 months on maximum tolerated doses, and combination therapy or switching to a different therapy may be necessary in cases of treatment resistance 1.
- It's essential to monitor for potential overlapping toxicities and drug-drug interactions when using combination therapies, and to adjust treatment strategies based on patient response and side effect profiles 1.
From the Research
High AM Cortisol
- High morning cortisol levels can be an indicator of Cushing's syndrome, a condition caused by excess cortisol in the body 2, 3, 4.
- Cushing's syndrome can be caused by a variety of factors, including ACTH-dependent and ACTH-independent diseases, and can be treated with a range of medications, including steroidogenesis inhibitors and glucocorticoid receptor antagonists 3, 4, 5.
- Medical treatment of Cushing's disease has been shown to be effective in controlling cortisol levels and improving clinical outcomes, with medications such as pasireotide, cabergoline, ketoconazole, and metyrapone being commonly used 3, 4, 5, 6.
- The choice of medication and treatment approach will depend on the individual patient's needs and circumstances, and may involve a combination of medications and other therapies 2, 4, 5.
- It is essential to monitor cortisol levels and adjust treatment as needed to achieve optimal control and minimize adverse effects 3, 4, 5, 6.
Treatment Options
- Metyrapone has been shown to be effective in controlling cortisol levels in patients with Cushing's syndrome, with significant improvements in biochemical parameters and clinical outcomes 3.
- Combination therapy with mitotane, metyrapone, and ketoconazole has been used as an alternative to rescue adrenalectomy in patients with severe ACTH-dependent Cushing's syndrome, with good efficacy and safety profiles 5.
- Osilodrostat is a new medication that has been shown to be effective in controlling cortisol levels in patients with Cushing's disease, with a rapid onset of action and good safety profile 4, 6.
- Pasireotide and cabergoline have also been used to treat Cushing's disease, with variable efficacy and safety profiles 6.