Metyrapone for Long-Term Medical Management of Cushing’s Syndrome

Cushing’s syndrome is characterized by any cause of excess cortisol in the blood and produces many physiologic consequences. Left untreated, Cushing’s is associated with significant morbidity and mortality. Seventy percent of endogenous cases of Cushing’s syndrome are secondary to a pituitary tumor; because of this, the primary mode of management is surgical resection of the tumor. Should hypercortisolism persist following surgical resection, further treatment options are limited. Metyrapone is an orphan medication that is often used in the diagnosis of the disease and occasionally for short-term treatment prior to surgery. Long-term treatment with metyrapone is usually discouraged due to the contradictory increase in ACTH production, acne, hirsutism, hyperkalemia, edema, and other mineralocorticoid effects. We present a patient with refractory Cushing’s syndrome successfully treated for nearly 6 years with metyrapone with minimal adverse effects. This orphan medication may be a viable long-term treatment option for this difficult disease. 1. Introduction Cushing’s syndrome is characterized by any cause of excess cortisol in the blood. Cortisol is a glucocorticoid that is responsible for the regulation of carbohydrate, protein, and lipid metabolism, it has anti-inflammatory properties, and its secretion is acutely increased during times of anxiety or stress. Cushing’s syndrome causes many physiologic consequences including centripetal obesity, impaired immune response, generalized muscle weakness, menstrual irregularities, hypertension, and premature death secondary to cardiovascular disease, infection, or suicide [1, 2]. Iatrogenic Cushing’s syndrome caused by exogenous glucocorticoid administration is the most common cause of excess cortisol levels. Of patients with endogenous causes of Cushing’s syndrome, 70% are secondary to a pituitary tumor; because of this, the primary mode of management is surgery to remove the tumor. Transsphenoidal surgery has up to an 80% remission rate for microadenomas and 50% for macroadenoma removal [3–5]. Should hypercortisolism persist following surgical resection, further treatment options are limited; a second attempt at transsphenoidal surgery, pituitary irradiation, adrenalectomy, steroidogenic inhibitors, or a combination of strategies is all that remains. The available steroidogenic inhibitors are difficult to use secondary to poor tolerability and lack of data regarding long-term efficacy. As a result, pharmacological treatment is often reserved for refractory Cushing’s, failed surgical cases, or patients who