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Journal Article
Review
Therapeutic Strategies for the Treatment of Severe Cushing's Syndrome.
Drugs 2016 March
Severe Cushing's syndrome presents an acute emergency and is defined by massively elevated random serum cortisol [more than 36 μg/dL (1000 nmol/L)] at any time or a 24-h urinary free cortisol more than fourfold the upper limit of normal and/or severe hypokalaemia (<3.0 mmol/L), along with the recent onset of one or more of the following: sepsis, opportunistic infection, intractable hypokalaemia, uncontrolled hypertension, heart failure, gastrointestinal haemorrhage, glucocorticoid-induced acute psychosis, progressive debilitating myopathy, thromboembolism or uncontrolled hyperglycaemia and ketocacidosis. Treatment focuses on the management of the severe metabolic disturbances followed by rapid resolution of the hypercortisolaemia, and subsequent confirmation of the cause. Emergency lowering of the elevated serum cortisol is most rapidly achieved with oral metyrapone and/or ketoconazole; if parenteral therapy is required then intravenous etomidate is rapidly effective in almost all cases, but all measures require careful supervision. The optimal order and combination of drugs to treat severe hypercortisolaemia-mostly in the context of ectopic ACTH-secreting syndrome, adrenocortical carcinoma or an ACTH-secreting pituitary adenoma (mainly macroadenomas)-is not yet established. Combination therapy may be useful not only to rapidly control cortisol excess but also to lower individual drug dosages and consequently the possibility of adverse effects. If medical treatments fail, bilateral adrenalectomy should be performed in the shortest possible time span to prevent the debilitating complications of uncontrolled hypercortisolaemia.
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