Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography

Sammanfattning: Adrenal tumours, discovered en passant in patients undergoing radiological examinations for non-adrenal disease, so-called adrenal incidentalomas, have increased dramatically in the recent era of more sophisticated diagnostic modalities such as high resolution multidetector computed tomography (CT) and magnetic resonance imaging (MRI). Furthermore, primary aldosteronism (PA) has been documented in several screening studies as being far more common than previously believed among hypertensive patients.In this thesis, a long-term follow-up cohort of patients who had undergone surgery for PA revealed that there was an excellent effect on blood-pressure, reduction of anti-hypertensive medication and hypokalaemia after surgery, even though the majority of these patients still required some anti-hypertensive medication. This was also true, in the higher than expected number of dominant nodular hyperplasia (nIHA) found in the study, but was slightly less pronounced than in aldosterone producing adenomas (APA).  Surgery was thus effective in lateralized PA.Metomidate positron emission tomography (MTO-PET) was explored in relation to histopathology in post-operative patients and found to be highly specific and sensitive in categorizing adrenocortical disease. Also, a higher standardized uptake value (SUV) ratio between tumours and normal adrenal cortex was found in hormonally hypersecreting adenomas as well as in adrenocortical cancer (ACC). The resolution limited the diagnosis of small tumours (<1-1.5 cm).MTO-PET was compared to standard radiological modalities (CT and MRI) in the diagnostic work-up of adrenal incidentalomas. All three modalities categorized and characterized the lesions well, with MTO-PET showing the highest sensitivity and specificity.  However this method is currently recommended to be used as complementary to the others in unclear cases, due to high costs and less availability.The resolution of MTO-PET was improved with respect to less noise and better delineation of small tumours when applying masked volume-wise principal component analysis (MVW-PCA), which will possibly enable future detection of small tumours in PA patients.Dexamethasone suppression treatment prior to MTO-PET examinations in PA patients decreased SUV in normal adrenal cortex but could not be shown to increase the SUV ratio between adenoma and normal cortex enabling better detection of small tumours, even though all the tumours were readily categorized in the study. Heterogenic SUV reactions to dexamethasone treatment indicate a need for further studies and refinement of the suppression method.In conclusion, long-term results of surgery for lateralized PA are good. MTO-PET is a highly sensitive and specific method for categorizing adrenocortical disease. Modulation of the method, e.g. by using MVW-PCA and refined dexamethasone suppression treatment, may improve the resolution of the method in delineating small tumours in PA, thus making MTO-PET a non-invasive and non-operator dependent future alternative to the currently recommended adrenal venous sampling (AVS) for lateralization diagnosis prior to surgery for PA.