Endocrine Abstracts

Introduction: Neuroendocrine tumors (NETs) are rare and their clinical behavior and prognosis correlates with mitotic rate and Ki-67 index. Most patients with advanced NET have liver metastases unresectable and somatostatin analogues are the initial therapy of choice but when disease progresses despite treatment and there are positive somatostatin receptors, peptide receptor radioligand therapy (PRRT), using lutetium-177, is a therapeutic option.

Clinical case: A 42-year-old male with episodes of fasting hypoglycemia was diagnosed with a well-differentiated low-grade NET G1 Insulin secretor, located in the pancreas body, with multiple liver metastases, after performing a 72-hour fasting test, abdominal magnetic resonance (MR) and fine needle aspiration by echoendoscopy. Biochemical data to highlight: chromogranin 592 ng/ml (≤ 100), gastrin 409 pg/ml (13–115), GOT 77 IU/l, GPT 87 IU/l, GGT 170 IU/l. Abdominal MR revealed multiple focal lesions distributed throughout the hepatic parenchyma, 5–30 mm in size and 2.5 × 1.7 cm pancreatic mass located in the distal body. 111-In-pentetreotide SPECT-CT showed multiple deposits of intense uptake and variable size in hepatic parenchyma with high expression of somatostatin receptors (SSTRs) and small deposit of discrete uptake in the pancreas body. Hypoglycemia, not controlled with diazoxide, disappeared with sandostatin LAR. Distal spleno-pancreatectomy was performed in June 2017 and the histological report confirmed a pancreatic NET G1 with numerous perineural infiltrations and vascular embolisms, free circumferential borders, and metastases in 4 of 21 isolated nodes. Post-surgery markers: chromogranin 737.4 ng/ml, gastrin >1,000 pg/ml. In SPECT-CT there were no significant changes in liver metastases, so PRRT with 177Lu-DOTATATE combined with Sandostatin LAR 30 mg IM/month was scheduled. Temozolomide-capecitabine chemotherapy was administered prior to 4 lutetium cycles initiated in June 2018 and completed in January 2019. After 2 cycles, chromogranin was 108.9 ng/ml and gastrin 32 pg/ml. The markers are negative since February 2019 and liver function progressively improved. Since October 2018, successive CT scans report a decrease in the size and uptake of hepatic focal lesions with an increase in central necrosis compatible with a partial response to treatment, and pentetreotide scintigraphy in March 2019 demonstrates a significant improvement in liver involvement.

Discussion: Pancreatic NETs are more aggressive but respond better to systemic agents. The benefit of conventional chemotherapy in malignant insulinoma is limited and PRRT with lutetium-177 have proven its efficacy and low toxicity so could be a suitable systemic therapy in selected patients.