Next-line protocol
Severe Cushing's Disease: Managing Hypercortisolism When Rapid Monotherapy Fails to Normalize Cortisol
Clinical scenario
This protocol applies to patients with severe Cushing's disease and severe hypercortisolism involving potentially life-threatening metabolic, psychiatric, infectious, or cardiovascular/thromboembolic complications — in whom an initial rapid-acting single-agent approach has not achieved adequate cortisol control.
Previous step — and why it was not enough
The initial approach used a rapid-acting adrenal steroidogenesis inhibitor as a single agent to quickly lower cortisol. Agents used in this setting may include:
osilodrostat
metyrapone
ketoconazole
etomidate (IV)
Goal not reached: rapid normalization of cortisol levels. This protocol describes the next step taken when that target is not met.
Treatment goal
Aggressive normalization of cortisol levels to reduce the risk of life-threatening complications in this severe clinical context.
Approach — partial overview
When a single steroidogenesis inhibitor proves insufficient, a combination of adrenal steroidogenesis inhibitors may be required to achieve cortisol control in severe hypercortisolism.
Full agent selection, sequencing, and monitoring details are available in the complete structured protocol below.
References
DOI: 10.1016/S2213-8587(21)00235-7
- For patients with severe disease, rapid normalization of cortisol is the most important goal.
- Patients with severe CD who have potentially life-threatening metabolic, psychiatric, infectious, or cardiovascular/thromboembolic complications also may benefit from preoperative medical therapy in select cases.
- For patients with severe hypercortisolism, combinations of steroidogenesis inhibitors may be necessary.
- In patients with severe disease, the primary goal is to treat aggressively to normalize cortisol levels (or cortisol action if using mifepristone).
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