The Role of Glucagon-Like Peptide 1 Receptor PET/CT With Ga-68-NODAGA-exendin in Localising an Insulinoma: Lessons From a Clinical Case

We present a clinical case highlighting the diagnostic challenges in a patient with an insulinoma. A 57-year-old lady initially presented with sweating on waking. Investigation documented a fasting blood glucose of 2 mmol/L (3.9-5.4) and the presence of anti-endomysial antibodies. On the basis of a diagnosis of Coeliac disease, the patient was commenced on a gluten free diet with apparent resolution of symptoms for 9 years. Subsequently, she re-presented with recurrent episodes of confusion which resolved with a ‘sugary’ drink. Consequently, she underwent a prolonged supervised fast: glucose 1.9 mmol/L (neuroglycopaenic symptoms), insulin 76 pmol/L (<20), c-peptide 763 nmol/L (<200) and β-hydroxybutyrate (BHB) 131 μmol/L (<2700). A diagnosis of endogenous hyperinsulinaemic hypoglycaemia resulted in radiological investigation (CT thorax/ abdomen/pelvis, MRI pancreas and endoscopic ultrasound [EUS] of pancreas) with no tumor identified. Due to persisting symptoms, in addition to dietary changes, diazoxide and octreotide were commenced. She was referred for a second opinion where a repeat 72-hour fast (at the time of hypoglycaemia symptoms) showed: glucose 2.3 mmol/L, Insulin 51 pmol/L, C-Peptide 513 pmol/L, BHB 1580 μmol/L and proinsulin 31 pmol/L (<10). Insulin antibody and sulphonylurea screens were negative. Her symptoms resolved after carbohydrate ingestion. Further imaging including a Ga-68-DOTATATE PET/CT, selective arterial calcium stimulation and hepatic venous sampling failed to localise an insulinoma. Despite pharmacological treatment hypoglycaemia continued to impede the patient’s quality of life and both octreotide and diazoxide were stopped due to side effects and minimal benefit. A glucagon-like peptide 1 receptor (GLP-1R) PET/CT scan with Ga-68-NODAGA-exendin-4 was performed and revealed uptake in a lesion in the ventral pancreatic body, suggestive of an insulinoma. A further EUS showed a corresponding 10 mm calcified area in the pancreatic body. The surgeon was unable to identify the tumor intra-operatively (macroscopically and ultrasound guided) and therefore performed a distal pancreatectomy which encompassed a 13 mm tumor. Histopathology demonstrated a 13 mm well differentiated, Grade 1 pancreatic neuroendocrine tumor (Ki67 1%) staining positively for AE1/AE3, synaptophysin, chromogranin and insulin (GLP-1R and pro-insulin staining awaited). Post-operatively, there was complete resolution of hypoglycaemia. In summary the learning points are the 9-year interval between initial presentation and confirmation of the diagnosis and the challenge of tumor localisation. There is no published evidence about gluten free diets reducing hypoglycaemia in insulinomas, but our patient described symptomatic improvement. GLP-1R are expressed in >90% of insulinomas and this case underlines the utility of GLP-1R PET/CT in insulinoma localisation.