Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 S17.3 | DOI: 10.1530/endoabs.35.S17.3

ECE2014 Symposia Cushings syndrome (3 abstracts)

Medical therapy for endogenous hypercortisolism

James Findling


Medical College of Wisconsin, Milwaukee, Wisconsin, USA.


The initial therapy for endogenous hypercortisolism (EH) or Cushing’s syndrome (CS) is almost always surgery. However, persistence or recurrence of EH is common and medical therapy may be needed to control the clinical and metabolic derangements associated with EH. Pituitary directed therapies include: Cabergoline, simple and well tolerated, cortisol (F) is normalized in 25-40% of patients but the effect is usually not enduring and Pasireotide, a somatostatin analog, reduces F in most patients with pituitary CS but normalizes F in only 25% with significant hyperglycemia in most patients. Adrenal-directed therapies include: ketoconazole which normalizes F in 50% of patients but may be associated with significant hepatotoxicity. Metyrapone, also not widely available, is often used to attenuate F secretion but there are no convincing studies showing sustained efficacy. Mitotane, adrenostatic and adrenolytic agent with significant GI/neurotoxicity, is usually reserved for patients with adrenocortical carcinoma but has also shown efficacy in other causes of EH. A new adrenostatic agent (LCI699) has also shown promise in phase II clinical trials. Etomidate, a parenterally administered hypnotic agent, is ideal for controlling EH in critically ill patients. Finally, a glucocorticoid receptor antagonist, mifepristone, has also been shown to improve clinical and metabolic consequences of EH but may cause hypokalemia, pituitary tumor enlargement, and endometrial thickening without any biochemical markers available to monitor the adequacy or inadequacy of its effect. Early detection of recurrent EH with late night salivary cortisol is important and medical, surgical, or radiotherapy should be considered long before there are any elevations of urine cortisol. The complexities and nuances of managing EH require careful individualization of therapy by an experienced endocrinologist.

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