Background: Benign insulinomas are the most prevalent cause of endogenous hyperinsulinaemic hypoglycaemia (EHH) in adults and due to their small size difficult to localise. Until now, the most sensitive test to localize the area of the potential insulinoma was the intra-arterial calcium stimulation test, an invasive procedure with its associated risk. In contrast to the other neuroendocrine tumors, benign insulinomas do not exhibit upregulated somatostatin receptors sutype 2 (sst2) but present with an increase in GLP-1 receptors (GLP-1R). GLP-1Rs can be targeted with GLP-1 analogues such as exendin-4. We aimed at prospectively comparing the accuracy of 111In-DOTA-exendin-4 SPECT/CT, 68Ga-DOTA-exendin-4 PET/CT, standardised 3-Tesla contrast-enhanced MRI (ceMRI), and non-standardised baseline imaging (ceCT/ceMRI) in patients with EHH.
Methods: We prospectively enrolled > 80 patients with neuroglycopenic symptoms due to EHH and no evidence for metastatic disease on conventional imaging using 111In-DOTA-exendin-4 SPECT/CT, 68Ga-DOTA-exendin-4 PET/CT and compared the sensitivity of the GLP-1R imaging to conventional imaging procedures (ceMRI and ceCT). The reference standard was surgery with histology and normalisation of blood glucose levels.
Findings: Patients were referred from whole Switzerland, Europa and USA. Baseline not standardised conventional imaging identified suspicious lesions in ca. 40% of the patients. Accuracy for PET/CT, SPECT/CT and standardised MRI, was 93·9%, 67·5% and 67·6%, respectively. GLP-1R imaging was useful in EHH in the context of benign sporadic insulinomas, in adult nesidioblastosis (68Ga-DOTA-exendin-4 PET/CT) and in patients with multiple endocrine neoplasia type 1 with multiple pancreatic lesions on conventional imaging. The size of the detected lesions was 425 mm.
Conclusion: GLP-1R PET/CT performed significantly better than SPECT/CT and conventional imaging and should be the diagnostic tool of choice in patients where localization fails with conventional imaging. Intra-arterial calcium stimulation test may only be indicated when GLP-1R PET/CT fails to localize the suspected lesion.
18 - 21 May 2019
European Society of Endocrinology