THU520 Successful Treatment Of Ectopic ACTH From Metastatic Gastrinoma With Temozolomide Monotherapy

Disclosure: A. Syeda: None. A. Khan: None. D. Larosa: None. P. Kunz: None. B. Esayag-Tendler: None. Background: Temozolomide is a promising therapeutic agent for the treatment of refractory ACTH-secreting pituitary tumors. However, its role in the management of ectopic ACTH secretion due to neuro endocrine tumors (NETs) has not been well elucidated. Case: A 46-year-old man with a refractory functional pancreatic NET/ high grade metastatic gastrinoma, post distal pancreatectomy and splenectomy, briefly on everolimus therapy, presented with altered mentation and worsening edema. Clinically he had proximal muscle weakness, anasarca and hypokalemia with a potassium of 2.8mmol/L (n:3.6-5.1 mmol/L). Further work up revealed AM cortisol 79.6 ug/dL (n:7-23 ug/dL), 24-hour urine cortisol was 1820 ug/d (n: < 60 ug/d), ACTH 807 pg/mL (n:7.2-63.3 pg/mL) and gastrin level >10,000 pg/mL (n:0-100 pg/mL). Imaging studies of the brain, chest, abdomen, and pelvis were unremarkable. Octreotide infusion at 100 mg/hour was started with a goal to decrease gastrin and ectopic ACTH production. There was no response to Octreotide even after 5 days of continuous infusion, hence it was switched to subcutaneous injection form to control diarrhea. Lutathera/Peptide receptor radionuclide therapy was considered but held off due to the patient's delirium. As hypercortisolism is associated with multiple risks including thromboembolic events, rapid reduction of cortisol biosynthesis was achieved with Ketoconazole. Other options to inhibit steroidogenesis were available; the goal was to decrease both ACTH and Gastrin levels and for this reason Temozolomide was started. It crosses the blood-brain-barrier and hence was a preferred agent in this patient as he was noted to have atypical cells in the CSF. He received Temozolomide 150 mg/m² for 5 days of a 28-day cycle. Subsequently, AM cortisol decreased to 3.4 ug/dL, ACTH and gastrin started to trend down to 144 pg/mL and 3505 pg/mL respectively. Thereafter, the patient was given steroids and ketoconazole as part of a block and replace strategy to avoid adrenal insufficiency and hypercortisolism respectively. Temozolomide was very well tolerated; there were different reasons to hold Capecitabine including severe thrombocytopenia. Bilateral adrenalectomy was discussed but deferred as the ACTH levels decreased. Clinically, the patient reported improved muscle strength, edema and weight decreased significantly. The hospital stay was complicated by several other comorbidities which were managed appropriately by a multidisciplinary approach. Conclusion: Temozolomide should be considered in ACTH producing NETs refractory to conventional treatment strategies. Presentation: Thursday, June 15, 2023