A High-Dose Cortisol Receptor Antagonist for the Management of Severe Hyperglycemia in a Patient With an Adrenocortical Carcinoma

摘要

The management of functional adrenocortical carcinoma (ACC) is challenging as it involves treating the underlying endocrinological abnormalities such as hypercortisolism. Competitive glucocorticoid receptor antagonist such as mifepristone (Korlym®) can be used to treat dysglycemia secondary to hypercortisolism. A 59-year-old male was admitted for dizziness and lightheadedness. Past medical history was significant for hypertension, and obesity. During evaluation, patient was found to have a random blood glucose of 663 mg/dL and a hemoglobin A1c of 14.4% with a previous of 5.8%. After admission, patient required 62.9 units of IV insulin over 9 hours to stabilize blood glucose. Due to the high insulin requirement and clinical presentation, a concern for hypercortisolism was considered and workup revealed an 8am cortisol level of 28.3 mcg/dL, and dexamethasone suppression test with cortisol of 50.4 mcg/dL, dexamethasone level 209 ng/dL and ACTH of <5 pg/mL. Patient was discharged on glargine 40 units SC BID and aspart 10 units SC TID AC. Seventeen days after discharge, patient was admitted with hyperglycemia (233 mg/dL), hypokalemia (2.5 mg/dL), abdominal pain, nausea, and vomiting. CT of abdomen revealed a 9.3 x 10.8 x 9 cm retroperitoneal mass arising from the left adrenal. Patient was started on mifepristone (Korlym®) 600mg PO daily while inpatient as his acute hyperglycemia was insufficiently controlled for consideration to open adrenalectomy. Within 24 hours of starting therapy, patient’s insulin requirement was de-escalated, and euglycemia was maintained for 20 days until surgery. Postoperative pathology demonstrated a 12.1cm resected tumor consistent with adrenocortical carcinoma. No clinical signs of adrenal insufficiency occurred postoperatively despite not stopping mifepristone (Korlym®) prior to surgery. Discussion: Adrenocortical carcinomas (ACC) are rare malignancies with an annual incidence of 0.7–2 cases per million population. They carry a poor prognosis with 5-year survival between 16–47%. The clinical presentation varies on the functional activity of these tumors and approximately 60% of them are cortisol secreting. The management of functioning-ACCs is challenging. Our patient presented with hyperglycemia secondary to hypercortisolism that was recurrent and difficult to control. He was started on mifepristone (Korlym®), a FDA approved potent competitive glucocorticoid receptor antagonist for the treatment of dysglycemia secondary to all forms of Cushing disease. In our patient, mifepristone provided a significant and rapid glycemic control, requiring to decrease the dose of insulin. Conclusion: This case demonstrates a safe and acute use of mifepristone (Korlym®) without initial titration in an inpatient monitored setting making this medication a viable option for management and optimization of hyperglycemia secondary to hypercortisolism.