From the Guidelines
Elevated cortisol levels, known as hypercortisolism or Cushing's syndrome, require prompt medical attention and a comprehensive treatment approach, with the most recent and highest quality study 1 suggesting that treatment depends on the underlying cause, with options including medication, surgery, radiation therapy, or a combination of these.
Treatment Options
- For cortisol-producing tumors, surgical removal is often the first-line treatment, such as transsphenoidal surgery for pituitary adenomas or adrenalectomy for adrenal tumors.
- When surgery isn't possible, medications like ketoconazole (400-1200 mg daily), metyrapone (250-750 mg every 4 hours), or mitotane (2-6 g daily in divided doses) can block cortisol production, as recommended by 1.
- Mifepristone (300-1200 mg daily) blocks cortisol receptors and may help manage glucose levels in Cushing's syndrome.
- For pituitary-dependent disease, pasireotide (0.6-0.9 mg twice daily by injection) may be effective, although its use is not recommended in children, as stated in 1.
Lifestyle Modifications
- Regular exercise, adequate sleep, stress management techniques, and a balanced diet low in simple carbohydrates are important lifestyle modifications.
- Untreated hypercortisolism can lead to serious complications including diabetes, hypertension, osteoporosis, increased infection risk, and psychological disturbances.
Monitoring and Follow-up
- Regular monitoring of cortisol levels and potential side effects is essential during treatment, as is addressing secondary health issues like bone loss, hypertension, and metabolic abnormalities, as emphasized in 1.
- Change in treatment should be considered if cortisol levels are persistently elevated after 2–3 months on maximum tolerated doses, and combination therapy can be considered if cortisol does not normalize but is reduced and/or there is some clinical improvement.
From the Research
Implications of Elevated Cortisol Levels
- Elevated cortisol levels can lead to substantial morbidity and mortality if left untreated 2
- Hypercortisolism can result in serious health complications, including increased blood pressure, kalaemia, and glycaemia 3
- Severe Cushing's syndrome can threaten life in the short term, making rapid control of cortisol levels crucial 3
Treatment Options for Elevated Cortisol Levels
- Adrenally directed medical therapies, such as ketoconazole, metyrapone, osilodrostat, mitotane, and etomidate, can inhibit adrenal steroidogenesis and reduce cortisol levels 2, 4
- Combination therapy with metyrapone and ketoconazole can provide rapid control of endocrine cancer-related life-threatening hypercortisolism 3
- Metyrapone treatment can normalize urinary-free cortisol (UFC) and late-night salivary cortisol (LNSC) levels in patients with Cushing's syndrome 5
- Mitotane, metyrapone, and ketoconazole combination therapy can be an effective alternative to rescue adrenalectomy for severe ACTH-dependent Cushing's syndrome 6
Monitoring and Management of Treatment
- Patients on adrenally directed medical therapies require careful dose titration and monitoring to ensure safety and effectiveness, while avoiding hypoadrenalism 2
- Regular measurement of UFC and LNSC levels can help assess the effectiveness of treatment and guide dose adjustments 5
- Patients should be instructed on the importance of close monitoring and potential side effects, such as hepatotoxicity and increased androgen and mineralocorticoid production 4