Category: Pituitary Disorders/Neuroendocrinology
Objective : Proximal muscle weakness and neuropsychiatric manifestations are common presentations of hypercortisolism. We present a case of improvement in muscle strength and psychiatric symptoms in a patient with persistent Cushing disease (CD) treated with mifepristone (Korlym®, Corcept Therapeutics), a competitive glucocorticoid receptor antagonist, after unsuccessful transsphenoidal surgery (TSS) and previous treatment with cabergoline and ketoconazole.
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Case Presentation: A 51-year old female patient with persistent CD post-TSS, who was previously treated with cabergoline and ketoconazole, presented in January 2017 for evaluation for weight gain. Her disease had progressed, and she experienced an 80-pound weight gain within a few months of discontinuing ketoconazole. In May 2017, she also developed type 2 diabetes (HbA1c 6.6%), obstructive sleep apnea, severe muscle weakness, and was discovered immobilized and urinating and defecating on couch. She had also attempted suicide in June 2015 and had a history of bipolar disorder with manic episodes. She was treated with 7 medications, including antipsychotics, anxiolytics, and antidepressants.
Mifepristone was initiated in May 2017; by month 5 of treatment, the patient had experienced complete resolution of her muscle weakness and improvement in psychiatric symptoms and moved out of her rehabilitation facility. Patient had discontinued 5 of 7 psychiatric medications by month 6, and, as of September 2018, had experienced a 56-lb weight loss, improvement in HbA1c to 5.6%, resolution of sleep apnea. She now takes 1 psychiatric medication (sertraline). She continues to demonstrate increased socialization with her family, self-sufficiency with daily activity, and lives independently without need for nursing care.
Mood disorders and anxiety are common psychiatric diseases associated with hypercortisolism. High levels of cortisol can cause significant changes to the structure and function of the hippocampus, amygdala, and prefrontal cortex resulting in neuropsychiatric disorders. This case highlights that treatment with mifepristone can be effective following unsuccessful TSS in improving muscle strength and psychiatric manifestations associated with hypercortisolism.