Executive summary of the consensus document for the management of severe Cushing's syndrome: Consensus document of the Neuroendocrinology Focus Group of the Spanish Society of Endocrinology and Nutrition (SEEN).

Severe Cushing's syndrome (SCS) is usually defined as a CS with urinary free cortisol (UFC) levels above five times the upper limit of normal or associated with severe complications of hypercortisolism. Combination therapy with ketoconazole and metyrapone is a useful option for these patients. Osilodrostat is the most potent and effective oral drug in monotherapy for the treatment of SCS. For cases with very severe hypercortisolism and/or oral intolerance, etomidate is the most effective and rapid drug for reducing cortisol levels. Bilateral adrenalectomy may be indicated in cases of life-threatening severe hypercortisolism, but UFC should be reduced before surgery to reduce the perioperative morbimortality. Prompt treatment of comorbidities and thrombo- and infection prophylaxis are recommended. In conclusion, a rapid control of hypercortisolism is vital in SCS, and for this purpose combination therapy or potent drugs with a rapid onset of action such as etomidate or osilodrostat are indicated.