Mifepristone for management of Cushing's syndrome.

Cushing's syndrome is a debilitating endocrine disorder caused by elevated circulating glucocorticoid levels. Although uncommon, Cushing's syndrome is associated with significant morbidity necessitating rapid reversal of hypercortisolemia. Primary therapy for most patients with Cushing's syndrome is surgical, but many patients will require additional treatments with radiation or drugs. Although several options for drug therapy exist, few are readily available and all have dose-limiting adverse effects. Mifepristone (RU 486), a first-in-class glucocorticoid receptor antagonist, was approved by the United States Food and Drug Administration in 2012 for use in Cushing's syndrome to control hyperglycemia in patients who are not surgical candidates or have not achieved remission from surgery. The drug is approved for oral once-daily administration. In its pivotal trial, 60% of patients responded to mifepristone with significant improvements in glycemic control and 38% had a reduction in diastolic blood pressure. The most common adverse events were nausea, fatigue, headache, endometrial hyperplasia, and hypokalemia. Adrenal insufficiency occurred in fewer than 5% of patients. The recommended starting dosage of mifepristone is 300 mg/day. The dosage may be increased every 2-4 weeks up to a maximum of 1200 mg/day, although it should not exceed 20 mg/kg/day. Significant drug-drug interactions exist due to mifepristone's effects on a number of cytochrome P450 enzymes. Despite its limitations, mifepristone is a welcome addition and an appropriate alternative to the available drug therapy for Cushing's syndrome.

Molecular markers in thyroid cytology: diagnostic and prognostic implications.

The discovery of thyroid nodules in the general population has risen markedly with the greater use of ultrasound resulting in increasing use of ultrasound-guided fine needle aspiration (FNA) biopsy. Although FNA can identify the majority of nodules as either benign or malignant, one-third of aspirates demonstrate indeterminate cytologic characteristics. Though most of these nodules will be pathologically benign, thyroid surgery has usually been needed to make an accurate diagnosis, and the extent of surgery needed (lobectomy versus total thyroidectomy) is difficult to predict in advance. New molecular techniques are being investigated and used clinically to improve decision making in patients with thyroid nodules with indeterminate cytology. These molecular markers have the potential to help clinicians decide which patients may be monitored without thyroid surgery, and also the optimal strategy when surgery is felt to be necessary.