MON-318 Selective ACTH Sampling in Localizing Source of ACTH in Von Hippel Lindau Disease with Pancreatic Neuroendocrine Tumour and Renal Cell Carcinoma

Background: Cushing’s syndrome (CS) in a patient with VHL has been attributed to a number of possible causes; pancreatic NET and renal cell carcinoma. The precise location of ectopic ACTH aid enormously in the management of VHL. Clinical case: A 31-year-old woman with Type 2 diabetes and family history of VHL presented with florid features of CS in her second trimester of pregnancy. A diagnosis of ACTH dependent CS was made based on elevated 24h urinary cortisol (1122 and 2448nmol/24hr, n<150-800), midnight cortisol (1322nmol/L, n<220nmol/L) and a detectable ACTH level (18.8pg/mL, n<10pg/mL). She underwent emergency caesarean section due to pre-eclampsia at 28 week gestation. Post-delivery, her morning cortisol was 2823nmol/L (n:171-536nmol/L). MRI pituitary was reported as normal. CT abdomen showed an enlarged pancreas which was almost completely cystic and a right renal mass (3.7 X 2.6 X 4cm). Serum chromogranin A was elevated (530.2ng/mL, n:27-94). 24h urinary free metanephrine was normal. Selective ACTH sampling was done together with bilateral inferior petrosal sinus sampling to elicit source of ACTH. Increased gradient of ACTH level compared to the periphery (138.9pg/mL vs. samples from IVC:115.1 pg/mL, renal vein:100.2 pg/mL) was detected from the hepatic vein that drains the pancreas via the portal venous system. Ketoconazole and metyrapone were given to control the cortisol level close to 600nmol/L prior to surgery. Preoperatively, IV hydrocortisone 100mg was administered, with additional 50mg given every 4 hours intraoperatively. Total pancreatectomy and right nephrectomy were performed. Inotropic support was required five hours into the surgery. Hydrocortisone was tapered down to a maintenance dose of 10mg, 5mg and 2.5mg TDS over 7 days. A week after surgery, am cortisol was 103nmol/L suggesting successful removal of ectopic ACTH source. Histopathological examination identified a solid tumour (18X12X12 mm) at the pancreatic tail which stained positive to Chromogranin A, synaptophysin and weakly positive to CD56. The mitoses was 0-1/10hpf with a Ki67 index of 2%. ACTH staining was positive. The renal mass was a Grade 1 clear cell renal cell carcinoma with equivocal ACTH staining. Two months later, there was resolution of cushingoid features. DOTATE and FDG/PET scans along with close surveillance using serum Chromogranin A and 6 monthly abdominal imaging were planned. Conclusion: When managing VHL with CS, there is always a possibility of more than one source of ACTH production. In delineating the cause of CS the use of selective ACTH sampling may be considered where functional imaging (DOTATATE) is unavailable. Reference : (1) Tamura K, Nishimori I, Ito T, Yamasaki I, Igarashi H, Shuin T. Diagnosis and management of pancreatic neuroendocrine tumor in von hippel-lindau disease. World J Gastroenterol. 2010;16(36):4515-4518. doi:10.3748/wjg.v16.i36.4515