Mifepristone as Bridge or Adjunct Therapy in the Management of Challenging Cushing Disease Cases.

Establishing a definitive diagnosis of Cushing disease (CD), given its clinical and biochemical heterogeneity, initiating effective treatment to control the effects of hypercortisolism, and managing recurrence are challenging disease aspects to address. Mifepristone is a competitive glucocorticoid receptor antagonist that is approved in the US by the Food and Drug Administration to control hyperglycemia secondary to endogenous hypercortisolism (Cushing syndrome) in patients who have glucose intolerance or type 2 diabetes mellitus and have failed surgery or are not candidates for surgery. Herein, we describe 6 patients with CD who received mifepristone as adjunct/bridge therapy in the following clinical settings: to assess clinical benefits of treatment for suspected recurrent disease, to control hypercortisolism preoperatively for severe disease, to control hypercortisolism during the COVID-19 pandemic, and to provide adjunctive treatment to radiation therapy. The patients were treated at multiple medical practice settings. Mifepristone treatment in each of the described cases was associated with clinical improvements, including improvements in overall glycemia, hypertension, and weight loss. In addition, in one case where biochemical and radiological evidence of disease recurrence was uncertain, clinical improvement with mifepristone pointed toward likely disease recurrence. Adverse events associated with mifepristone reported in the 6 cases were consistent with those previously reported in the pivotal trial and included cortisol withdrawal symptoms, antiprogesterone effects (vaginal bleeding), hypothyroidism (treated with levothyroxine), and hypokalemia (treated with spironolactone). These cases show how mifepristone can potentially be utilized as a therapeutic trial in equivocal cases of CD recurrence; as a presurgical treatment strategy, particularly during the COVID-19 pandemic; and as bridge therapy, while awaiting the effects of radiation.

Growth hormone replacement in patients with a history of malignancy: a review of the literature and best practice for offering treatment.

Previous studies have implicated the growth hormone (GH)/IGF-I axis as an important mediator of cancer risk in humans and animals. Evidence supporting this notion is derived from animal studies, epidemiological observations, patients with acromegaly and from therapeutic manipulation of GH and IGF-I actions. Therefore, the use of GH therapy in patients with a history of malignancy raises hypothetical safety concerns. Reassuringly, GH therapy in childhood cancer survivors has not been confirmed to increase the cancer risk. Conversely, the risk of occurrence of a second neoplasm may be increased, with meningiomas being the most common tumor. In light of these findings, we propose considering GH therapy to be based on each individual's circumstance and commenced at least 2 years after cancer remission is achieved with close monitoring during therapy. More long-term data are needed on the safety of GH replacement therapy in GH-deficient adults with a history of malignancy.