Ruth Therese Casey, Deborah Saunders, Benjamin George Challis, Deborah Pitfield, Heok Cheow, Ashley Shaw and Helen Lisa Simpson
Multiple endocrine neoplasia type 1 (MEN1) is a hereditary condition characterised by the predisposition to hyperplasia/tumours of endocrine glands. MEN1-related disease, moreover, malignancy related to MEN1, is increasingly responsible for death in up to two-thirds of patients. Although patients undergo radiological and biochemical surveillance, current recommendations for radiological monitoring are based on non-prospective data with little consensus or evidence demonstrating improved outcome from this approach. Here, we sought to determine whether cumulative radiation exposure as part of the recommended radiological screening programme posed a distinct risk in a cohort of patients with MEN1.
Patients and study design
A retrospective review of 43 patients with MEN1 attending our institution between 2007 and 2015 was performed. Demographic and clinical information including phenotype was obtained for all patients. We also obtained details regarding all radiological procedures performed as part of MEN1 surveillance or disease localisation. An estimated effective radiation dose (ED) for each individual patient was calculated.
The mean ED for the total patient cohort was 121 mSv, and the estimated mean lifetime risk of cancer secondary to radiation exposure was 0.49%. Patients with malignant neuroendocrine tumours (NETS) had significantly higher ED levels compared to patients without metastatic disease (P < 0.0022).
In MEN1, radiological surveillance is associated with clinically significant exposure to ionising radiation. In patients with MEN1, multi-modality imaging strategies designed to minimise this exposure should be considered.
Benjamin G Challis, Andrew S Powlson, Ruth T Casey, Carla Pearson, Brian Y Lam, Marcella Ma, Deborah Pitfield, Giles S H Yeo, Edmund Godfrey, Heok K Cheow, V Krishna Chatterjee, Nicholas R Carroll, Ashley Shaw, John R Buscombe and Helen L Simpson
In adults with hyperinsulinaemic hypoglycaemia (HH), in particular those with insulinoma, the optimal diagnostic and management strategies remain uncertain. Here, we sought to characterise the biochemical and radiological assessment, and clinical management of adults with HH at a tertiary centre over a thirteen-year period.
Clinical, biochemical, radiological and histological data were reviewed from all confirmed cases of adult-onset hyperinsulinaemic hypoglycaemia at our centre between 2003 and 2016. In a subset of patients with stage I insulinoma, whole-exome sequencing of tumour DNA was performed.
Twenty-nine patients were identified (27 insulinoma, including 6 subjects with metastatic disease; 1 pro-insulin/GLP-1 co-secreting tumour; 1 activating glucokinase mutation). In all cases, hypoglycaemia (glucose ≤2.2 mmol/L) was achieved within 48 h of a supervised fast. At fast termination, subjects with stage IV insulinoma had significantly higher insulin, C-peptide and pro-insulin compared to those with insulinoma staged I–IIIB. Preoperative localisation of insulinoma was most successfully achieved with EUS. In two patients with inoperable, metastatic insulinoma, peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE rapidly restored euglycaemia and lowered fasting insulin. Finally, in a subset of stage I insulinoma, whole-exome sequencing of tumour DNA identified the pathogenic Ying Yang-1 (YY1) somatic mutation (c.C1115G/p.T372R) in one tumour, with all tumours exhibiting a low somatic mutation burden.
Our study highlights, in particular, the utility of the 48-h fast in the diagnosis of insulinoma, EUS for tumour localisation and the value of PRRT therapy in the treatment of metastatic disease.