From the Guidelines
The protocol for managing hypercortisolism (Cushing's syndrome) involves rapid normalization of cortisol levels using medications such as osilodrostat, metyrapone, ketoconazole, or etomidate, with the goal of achieving response within hours or days 1.
Treatment Options
- Medical therapies: osilodrostat, metyrapone, and ketoconazole are effective in reducing cortisol levels, either alone or in combination, with response typically seen within hours or days 1.
- Dosing: metyrapone can be prescribed at a dose of 15 mg/kg every 4 h for 6 doses, alternatively 300 mg/m2 every 4 h, with a usual dose of 250–750 mg every 4 h, while ketoconazole can be initiated at 400–600 mg per day in 2–3 divided doses, increased to 800–1,200 mg per day until cortisol levels normalize 1.
- Bilateral adrenalectomy (BLA): reserved for patients with severe refractory Cushing disease or life-threatening emergencies, as it can lead to Nelson syndrome, a potentially life-threatening secondary consequence 1.
Special Considerations
- Pediatric patients: medical therapies should be used to normalize cortisol levels in preparation for surgery or while awaiting a biochemical response to radiotherapy, due to the limited role of long-term medical therapy in children 1.
- Surgical options: unilateral adrenalectomy is recommended for patients with unilateral cortisol-secreting adrenal masses and clinically apparent Cushing’s syndrome, with minimally-invasive surgery (MIS) preferred when feasible 1.
From the Research
Diagnostic Approach
- The recommended diagnostic approach for Cushing's syndrome includes appropriate screening, confirmation of hypercortisolism, and determination of etiology 2
- Screening patients with suspected Cushing's syndrome is recommended with 24-h urine cortisol, bedtime salivary cortisol and/or 1 mg dexamethasone suppression test 3
Treatment Options
- First-line treatment is surgical removal of the source of cortisol overproduction 2, 3
- Second-line therapies include steroidogenesis inhibitors for any cause of Cushing's syndrome, pituitary radiation (with or without steroidogenesis inhibitors) for Cushing's disease, and bilateral adrenalectomy for ACTH-dependent causes of Cushing's syndrome 3
- Medical therapy for Cushing's disease is primarily used to control hypercortisolism in patients whose disease persists or with recurrent disease after pituitary surgery, including those awaiting the salutary effects of radiation therapy 4
- Medical treatment is also often required while waiting for radiation effects to take place, or in cases of severe or life-threatening hypercortisolism 5
Medical Management
- Steroidogenesis inhibitors, centrally acting agents, and glucocorticoid receptor antagonists are currently available to treat hypercortisolism 4
- Novel agents, including new inhibitors for steroidogenic enzymes, pituitary-directed drugs, and glucocorticoid receptor antagonists, are in development 5
- Medical treatment has progressed from a few steroidogenesis inhibitors to three novel drug groups, with potential targets that may decrease adrenocorticotrophic hormone and/or cortisol excess 5
Post-Therapy Monitoring
- Lifelong posttherapy monitoring is required to treat comorbidities and detect recurrence 2