MON-508 - Successful Use of Osilodrostat as Monotherapy Strategy for Severe Ectopic Cushing'S Syndrome: A Case Report

Introduction:
Ectopic adrenocorticotropic hormone secretion (EAS) is a rare subset of endogenous Cushing’s syndrome (CS) in which non-pituitary tumors secrete Adenocorticotropic Hormone (ACTH), which leads to rapid development of hypercortisolism and subsequent metabolic derangements. This can be life-threatening and can make treatment challenging. Osilodrostat is a newer and potent oral steroidogenesis inhibitor of 11β-hydroxylase that has shown to effectively inhibit cortisol production in cases of CS; however, there is limited literature on its use for EAS.

Case:
A 68-year-old female presented to the hospital due to chest pain and right-sided hip pain. On physical exam, she had a BP of 245/115 mmHg, generalized edema, thin skin, and diffuse ecchymosis. Initial laboratory findings showed hypokalemia (2.2 mmol/L, n 3.5-5.1 mmol/L). Imaging demonstrated a pathologic fracture at the right iliac bone and a mass in the left upper lung. Further laboratory workup revealed AM cortisol of 61.1 ug/dL (3.7-19.4ug/dL) and ACTH level at 305 pg/mL (6.0-50 pg/mL). Cortisol after 1mg-DST and 8mg-DST failed to suppress, LNSC of 6.15 mcg/dL (<= 0.09mcg/dL), and 24hr-UFC 3461.5 mcg/24 hr (4.0-50.0mcg/24h). CT abdomen showed a pathologic fracture at the right iliac bone, no adrenal lesion. CT Chest revealed a mass in the left upper lobe with metastatic lesions to the ribs and lymphadenopathy. Imaging of the brain was negative for sellar mass. Pathology of the right iliac bone biopsy was consistent with metastatic poorly differentiated carcinoma. These confirmed ACTH-dependent hypercortisolism secondary to ectopic ACTH production.

She was initiated on ketoconazole (KC) 200 mg BID. Initially, BP improved; however, she still required high doses of KCl and AM cortisol at 72.7 ug/dL; therefore, KC was increased to 300 mg TID. The patient was not a candidate for bilateral adrenalectomy. Follow-up labs with AM cortisol 44.6 ug/dL but persistent hypokalemia despite KC, five HTN agents, and KCl 180 mEq/day. She was then started on Osilodrostat 2 mg BID in addition to KC. However, a few days later, KC had to be discontinued due to elevated liver enzymes. She continued Osilodrostat monotherapy at 4 mg BID. A few weeks into treatment, her cortisol levels improved to 20.8 µg/dL, accompanied by normalization of BP and serum potassium (4.4 mmol/L). She has completed one cycle of chemotherapy and is scheduled to initiate immunotherapy. In addition, she is undergoing palliative radiotherapy for symptomatic bone metastases.

Conclusions
- Osilodrostat is effective as monotherapy in the treatment of severe EAS by providing effective control of hypercortisolism, resulting in rapid improvement of cortisol-driven metabolic complications.
- Osilodorstat should be considered when rapid biochemical control is required, when other steroidogenesis inhibitors are not tolerated, or when patients are poor surgical candidates.

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