Background: Cross-sectional imaging (e.g. CT/MRI) can not always reliably identify the site of ACTH secretion in Cushings disease (CD) or the ectopic ACTH syndrome (EAS). We report our experience of localising the source of ACTH-dependent Cushings syndrome, using functional imaging with 11C-methionine positron emission tomography (Met-PET).
Methods: Forty consecutive patients with: (i) de novo Cushings disease (n=18), (ii) residual or recurrent Cushings disease following previous pituitary surgery and/or radiotherapy (n=15) or (iii) ectopic Cushings syndrome (n=7) were imaged between 2011 and 2017. Patients underwent Met-PET and 3D gradient echo MRI of the sella. Co-registration of PETCT with MR images was performed to yield Met-PET/MRI. Detailed mapping of 11C -methionine uptake across the sella in three planes (coronal, sagittal and axial) was performed to allow correlation of functional data obtained from Met-PET with structural/anatomical data obtained from MRI. For those with EAS, additional Met-PET/CT studies of the neck, thorax and upper abdomen were performed.
Results: Eleven patients (60%) with de novo Cushings disease and 10 patients (67%) with recurrent/residual Cushings disease, but equivocal or negative cross-sectional imaging, had tumour successfully localized using Met-PET/MRI. In four patients (57%) with EAS, Met-PET/CT revealed sites of primary or metastatic disease, including in one patient with repeatedly negative cross-sectional imaging. Of the three remaining patients with EAS but negative Met-PET/CT, two also had negative cross-sectional and other functional (18F-FDG and/or 68Ga-PET-CT) imaging studies; in one patient, 68Ga-PET-CT identified a small pancreatic primary tumour.
Conclusions: We report findings in the largest cohort of patients with ACTH-dependent Cushings syndrome who have undergone functional imaging with Met-PET. Although this technique does not localize the site of ACTH-secretion in all cases, it is a useful adjunctive imaging modality for patients with negative/inconclusive findings from conventional imaging studies, especially in those with persistent/recurrent disease.