Mifepristone Use in Hypercortisolism from an Unknown Source: A Case Study

The diagnosis of Cushing syndrome (CS) can be challenging because clinical features overlap with numerous common disorders, the sensitivity and specificity of diagnostic tests are imperfect, and discordant biochemical findings are often obtained. Diagnosis and management are further complicated if a source of hypercortisolism is not readily apparent. We describe the medical management of a patient with suspected CS, whose initial evaluation did not reveal a source.

Case Description:

A 76-year-old man presented with metabolic disorders progressing during the previous 5 years, including 23 lbs of central weight gain, worsening diabetes mellitus type 2, and resistant hypertension. CS was suspected because 1) control of fasting glucose and HbA1c levels required 4 antidiabetic medications, 2) despite control of fasting glucose, postprandial glucose levels were uncontrolled, and 3) control of blood pressure required 5 antihypertensive medications plus a diuretic. The patient was evaluated for CS even though, except for central obesity, he lacked the typical physical features. Baseline biochemical findings included two overnight 1 mg dexamethasone suppression tests showing non-suppressed total cortisol and adequate dexamethasone levels, low DHEA-sulfate, and low-normal ACTH levels. Late-night salivary cortisol and urine free cortisol levels were normal. Evaluations of aldosterone, renin, and catecholamines were unremarkable. Although biochemical findings were consistent with primary adrenal hypercortisolism, a non-contrast adrenal CT scan report described the adrenal glands as normal in size and appearance. The patient was prescribed cortisol-directed therapy with mifepristone (Korlym®, Corcept Therapeutics; 300 mg q.d. titrated to 600 mg q.d.) and within 5 weeks of starting treatment, 3 of the 4 antidiabetic and 3 of the 5 antihypertensive medications were discontinued. After 79 weeks of treatment, HbA1c decreased from 6.8% to 5.6%, postprandial glucose normalized, blood pressure was controlled, and weight decreased by 29 lbs. Reinterpretation of the original CT scan by an adrenal expert after the favorable response to treatment confirmed the diagnosis of bilateral adrenal hyperplasia.

Discussion:

Patients with severe diabetes, resistant hypertension, obesity, and other metabolic disorders, who are outliers in terms of disease management complexity, should be viewed with a high index of suspicion for CS even in the absence of classical physical features. This case demonstrates that medical therapy should not be delayed if CS is suspected but a source is not identified. Mifepristone was an effective treatment while the search for the source continued.