Medically Refractory Cushing's Syndrome as a Paraneoplastic Manifestation of Esthesioneuroblastoma

Background: Esthesioneuroblastoma or olfactory neuroblastoma (ONB) is a rare malignancy of the sinonasal cavity derived from the olfactory epithelium. There are scattered reports of ectopic or paraneoplastic hormone secretion from these tumors.

Objectives: To report a case of medically uncontrollable ectopic Cushing's Syndrome necessitating prompt surgical management and a review of the literature surrounding this unique diagnosis and management.

Methods: This report describes a case of esthesioneuroblastoma presenting with acute hyperglycemia and electrolyte abnormalities. A review of the literature (PubMed and Medline) was performed with an emphasis on tumors with ectopic adrenocorticotropic hormone (ACTH) and management.

Results: A 52-year-old male presented with acute altered vision and new onset hyperglycemia. A head CT discovered an erosive skull base mass. Endoscopic biopsy revealed esthesioneuroblastoma and the patient was discharged pending further workup. Prior to tumor board evaluation and other consultations, the patient returned to the hospital with profound weakness, edema, and severe electrolyte abnormalities. Further workup revealed blood glucose of 342 mg/dL and ACTH of 344 pg/mL. The patient was aggressively medically managed for presumed paraneoplastic Cushing's syndrome. He ultimately failed medical management, necessitating surgical resection. Following surgery, the patient progressed well and was able to achieve resolution and medical control of his Cushing syndrome, with undetectable postoperative ACTH levels. The patient underwent adjuvant treatment with combined radiation and chemotherapy and recovered endocrine function. 5 year follow up demonstrated no evidence of disease.

A review of the current literature demonstrates fewer than 20 cases describing esthesioneuroblastoma with ectopic ACTH production. We present a unique case of acute onset Cushing's syndrome in a patient without typical Cushingoid features refractory to medical management. Ultimately surgical resection lead to resolution of endocrine symptoms related to excess ACTH.

Conclusion: Esthesioneuroblastomas are rare skull base tumor that can present with acute paraneoplastic secretion of ACTH. Treatment consists of medical management and surgical resection if indicated.

Fig. 1 Computerized tomography demonstrating cribriform erosion and skull base extension.

Fig. 2 Magnetic resonance imaging showing skull base erosion and intracranial extension.