SUN-071 - Olfactory Neuroblastoma: An Uncommon Source of Ectopic ACTH-Dependent Cushing Syndrome

Background: Cushing syndrome results from excess glucocorticoid exposure and is most commonly due to exogenous steroid use or tumors within the hypothalamic–pituitary–adrenal axis. Ectopic adrenocorticotropic hormone (ACTH) production from nonendocrine malignancies is rare. Olfactory neuroblastoma is an exceptionally uncommon source, with fewer than twenty cases reported in the literature.

Case: A 41-year-old man with hypertension and ADHD presented with severe epistaxis requiring nasal tamponade. Sinonasal endoscopy revealed a mass extending into the nasopharynx. MRI demonstrated an 8x6x7 cm contrast-enhancing lesion with extensive bony erosion, mass effect on the optic nerves, frontal lobes, and lateral ventricles, along with vasogenic edema, midline shift, and exophthalmos. Biopsy confirmed olfactory neuroblastoma. Surgical resection was precluded by unfavorable anatomy, and PET CT showed no metastatic disease. Chemotherapy was initiated.

He was subsequently hospitalized after one cycle with new-onset diabetic ketoacidosis (HbA1c 10.6%). He had positive glutamic acid decarboxylase antibodies and was started on basal bolus insulin with metformin. Weeks later, he re-presented after a fall without head trauma and was found to have acute bilateral frontal intraparenchymal hemorrhages in the setting of severe hypertension (up to 220/110 mmHg). Laboratory evaluation was notable for hypernatremia (149 mmol/L), hypokalemia (2.4 mmol/L), leukocytosis (12 K/µL), anemia (8 g/dL), severe thrombocytopenia (23 K/µL), and suppressed TSH (0.034 µIU/mL). Blood cultures grew Staphylococcus aureus and Cryptococcus species for which he was started on antibiotic and antifungal therapy. Transthoracic echocardiography revealed an ejection fraction of 40% with features of stress cardiomyopathy.

Endocrine evaluation demonstrated markedly elevated serum cortisol (134 µg/dL) and ACTH (365 pg/mL) without suppression after 4 mg of dexamethasone, 24-hour urine cortisol (> 4,768 mcg), and midnight salivary cortisol (> 1.000 mcg/dL). CT scan showed bilateral adrenal thickening, and pituitary MRI was unremarkable, consistent with ectopic ACTH production. Medical adrenal blockade with continuous etomidate infusion and ketoconazole resulted in rapid cortisol reduction and improvement in blood pressure, glycemic control, electrolyte abnormalities, cytopenias, and thyroid function. Bilateral adrenalectomy was deferred given the patient’s guarded prognosis from his primary malignancy even if he had definitive treatment for ectopic Cushing’s.

Conclusion: This case illustrates a rare cause of ectopic ACTH–dependent Cushing syndrome from olfactory neuroblastoma, presenting with multisystem decompensation. It highlights the profound systemic consequences of uncontrolled hypercortisolism and underscores the role of medical steroidogenesis blockade.

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