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Clinical Studies on Adrenocortical Tumours using  [11C]-metomidate Positron Emission Tomography
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper. (Endokrinkirurgi/Hellman)
2009 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Uppsala: Acta Universitatis Upsaliensis , 2009. , s. 33
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 486
HSV kategori
Forskningsprogram
kirurgi
Identifikatorer
URN: urn:nbn:se:uu:diva-108797ISBN: 978-91-554-7618-2 (tryckt)OAI: oai:DiVA.org:uu-108797DiVA, id: diva2:241074
Disputas
2009-11-14, Auditorium Minus, Museum Gustavianum, Uppsala, 09:15 (svensk)
Opponent
Veileder
Tilgjengelig fra: 2009-10-23 Laget: 2009-09-29 Sist oppdatert: 2009-10-23bibliografisk kontrollert
Delarbeid
1. Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas
Åpne denne publikasjonen i ny fane eller vindu >>Computed tomography, magnetic resonance imaging and 11C-metomidate positron emission tomography for evaluation of adrenal incidentalomas
2009 (engelsk)Inngår i: European Journal of Radiology, ISSN 0720-048X, E-ISSN 1872-7727, Vol. 69, nr 2, s. 314-23Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: Given the higher sensitivity of modern computed tomography (CT) scanners, adrenal incidentalomas are being discovered increasingly often. This implies a growing quantitative diagnostic and clinical problem. CT and/or magnetic resonance imaging (MRI) and usually thorough hormonal testing are routinely used to determine the origin of these lesions. Recently, positron emission tomography (PET) using the tracer (11)C-metomidate (MTO) has been established as an alternative diagnostic method with high sensitivity for identifying adrenocortical lesions. The aim of this study was to evaluate the clinical use and value of MTO-PET compared to CT and MRI in the characterisation and work-up of adrenal incidentalomas. METHODS: Initially, we retrospectively evaluated 20 adrenal incidentalomas in patients who had undergone CT, MRI and MTO-PET and from whom we had either histopathological diagnosis or clinical follow-up data. After this analysis we conducted a prospective study in order to compare the imaging modalities. In the latter study, 24 incidentalomas were imaged by CT, MRI and MTO-PET and the results were correlated to those from histopathology (n=8) and clinical diagnosis after follow-up (n=16). RESULTS: In the retrospective analysis, MRI and especially MTO-PET, correlated well to histopathology and clinical diagnosis after follow-up, whereas specificity with CT was low. This was possibly due to the presence of several haematomas/fibrosis which were misdiagnosed as adrenocortical adenomas. In the prospective cohort, sensitivity and specificity with CT were 0.71 and 1.0, respectively, and further characterisation by MRI increased these values to 0.86 and 1.0, whereas maximum sensitivity and specificity were reached when MTO-PET was added. CONCLUSION: The diagnosis of an adrenocortical adenoma may be established by CT in most patients and by MRI in an additional number. For the few remaining patients needing further characterisation, MTO-PET is advantageous as an additional imaging modality.

Emneord
adrenal, incidentalomas, metomidate, PET, MRI, CT
HSV kategori
Forskningsprogram
Diagnostisk radiologi
Identifikatorer
urn:nbn:se:uu:diva-104627 (URN)10.1016/j.ejrad.2007.10.024 (DOI)000264220600017 ()18082990 (PubMedID)
Tilgjengelig fra: 2009-05-29 Laget: 2009-05-29 Sist oppdatert: 2017-12-13bibliografisk kontrollert
2. Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism
Åpne denne publikasjonen i ny fane eller vindu >>Long-term effects of surgical correction of adrenal hyperplasia and adenoma causing primary aldosteronism
Vise andre…
2010 (engelsk)Inngår i: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, nr 2, s. 133-137Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

PURPOSE: The purpose of this is to study long-time results of surgery for primary aldosteronism. MATERIALS AND METHODS: Thirty patients operated on for primary aldosteronism were followed for an average of 7 years. All but five required potassium substitution. Systolic as well as diastolic hypertension (mean 157/93 mmHg) was present necessitating one to five antihypertensive drugs daily (mean 2.33). Preoperative indications for surgery included presumed adenoma (aldosterone-producing adenoma (APA)) or in one case unilateral dominance of hyperplasia. RESULTS: Histopathology was classified into adenoma (n = 9), dominant nodule (n = 16), and general hyperplasia without dominating nodules (n = 5), demonstrating a higher frequency of hyperplasia than anticipated. Long-term results revealed well-controlled blood pressure (BP; mean 134/80 mmHg). Antihypertensive medication was reduced (average of 1.78 per day), but only 36% of the patients were taken off these drugs completely. S-Aldosterone was normalized. All but one (a recurrence) were normokalemic without potassium substitution at follow-up. The APA group needed less medication (median 0.5 vs. 1.5 and 2 per day) and more patients in this group were totally medication free (50%). Two recurrences occurred in the group with general hyperplasia without dominating nodules. CONCLUSION: Nodular hyperplasia is more common than anticipated. Hypersecretion of aldosterone may be released from a large nodule identified as an adenoma, as well as from a generally hyperplastic gland that has not been identified as such. Nevertheless, surgery for lateralized disease results in good long-term control of BP with less antihypertensive medication. However, patients with dominant nodule or general hyperplasia without dominating nodules need more postoperative treatment than patients with APA. The majority of patients do not achieve normotension without medications, but they do become normokalemic.

Emneord
Primary aldosteronism, Long-time follow-up, Surgery, Nodular hyperplasia
HSV kategori
Forskningsprogram
Kirurgi
Identifikatorer
urn:nbn:se:uu:diva-104657 (URN)10.1007/s00423-009-0498-4 (DOI)000274652000006 ()19418066 (PubMedID)
Tilgjengelig fra: 2009-05-29 Laget: 2009-05-29 Sist oppdatert: 2017-12-13bibliografisk kontrollert
3. [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings
Åpne denne publikasjonen i ny fane eller vindu >>[11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings
Vise andre…
2006 (engelsk)Inngår i: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 91, nr 4, s. 1410-4Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

CONTEXT: Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging. OBJECTIVE: We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal tumors. DESIGN: Seventy-five histopathological examinations from 73 patients were retrospectively analyzed. SETTING: All examinations were performed at a referral center. PATIENTS: Patients who were operated or biopsied due to adrenal tumors had histopathological diagnoses of adrenocortical adenoma (n = 26), adrenocortical cancer (ACC; n = 13), adrenocortical hyperplasia (n = 8), pheochromocytoma (n = 6), metastasis (n = 3), and tumors of nonadrenal origin (n = 19). MAIN OUTCOME MEASURES: The main outcome measures were statistical analyses and findings while scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection. RESULTS: Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from normal adrenocortical tissue. SUV was higher in aldosterone-hypersecreting adenomas, and the SUV ratio between the tumor and the contralateral gland was significantly higher in all hormonally hypersecreting adenomas as well as in ACC. CONCLUSION: MTO-PET is a specific and sensitive method for diagnosing adrenocortical tumors. MTO-PET is useful in the imaging work-up of adrenal incidentalomas and may be beneficial for the examination of patients with primary aldosteronism or ACC.

Emneord
Adrenal Cortex Neoplasms/*pathology/*radionuclide imaging, Aged, Antineoplastic Agents/*diagnostic use, Data Interpretation; Statistical, Ethics, Etomidate/*analogs & derivatives/diagnostic use, Female, Humans, Image Processing; Computer-Assisted, Male, Middle Aged, Positron-Emission Tomography, Radiopharmaceuticals/diagnostic use
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-17464 (URN)10.1210/jc.2005-2273 (DOI)16403816 (PubMedID)
Tilgjengelig fra: 2008-06-24 Laget: 2009-01-30 Sist oppdatert: 2017-12-08bibliografisk kontrollert
4. Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography
Åpne denne publikasjonen i ny fane eller vindu >>Masked volume wise Principal Component Analysis of small adrenocortical tumours in dynamic [11C]-metomidate Positron Emission Tomography
Vise andre…
2009 (engelsk)Inngår i: BMC Medical Imaging, ISSN 1471-2342, E-ISSN 1471-2342, Vol. 9:6Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND: In previous clinical Positron Emission Tomography (PET) studies novel approaches for application of Principal Component Analysis (PCA) on dynamic PET images such as Masked Volume Wise PCA (MVW-PCA) have been introduced. MVW-PCA was shown to be a feasible multivariate analysis technique, which, without modeling assumptions, could extract and separate organs and tissues with different kinetic behaviors into different principal components (MVW-PCs) and improve the image quality. METHODS: In this study, MVW-PCA was applied to 14 dynamic 11C-metomidate-PET (MTO-PET) examinations of 7 patients with small adrenocortical tumours. MTO-PET was performed before and 3 days after starting per oral cortisone treatment. The whole dataset, reconstructed by filtered back projection (FBP) 0-45 minutes after the tracer injection, was used to study the tracer pharmacokinetics. RESULTS: Early, intermediate and late pharmacokinetic phases could be isolated in this manner. The MVW-PC1 images correlated well to the conventionally summed image data (15-45 minutes) but the image noise in the former was considerably lower. PET measurements performed by defining "hot spot" regions of interest (ROIs) comprising 4 contiguous pixels with the highest radioactivity concentration showed a trend towards higher SUVs when the ROIs were outlined in the MVW-PC1 component than in the summed images. Time activity curves derived from "50% cut-off" ROIs based on an isocontour function whereby the pixels with SUVs between 50 to 100% of the highest radioactivity concentration were delineated, showed a significant decrease of the SUVs in normal adrenal glands and in adrenocortical adenomas after cortisone treatment. CONCLUSION: In addition to the clear decrease in image noise and the improved contrast between different structures with MVW-PCA, the results indicate that the definition of ROIs may be more accurate and precise in MVW-PC1 images than in conventional summed images. This might improve the precision of PET measurements, for instance in therapy monitoring as well as for delineation of the tumour in radiation therapy planning.

HSV kategori
Forskningsprogram
Datoriserad bildanalys
Identifikatorer
urn:nbn:se:uu:diva-104646 (URN)10.1186/1471-2342-9-6 (DOI)19386097 (PubMedID)
Tilgjengelig fra: 2009-04-22 Laget: 2009-05-29 Sist oppdatert: 2017-12-13bibliografisk kontrollert
5. 11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism
Åpne denne publikasjonen i ny fane eller vindu >>11C-metomidate positron emission tomography after dexamethasone suppression for detection of small adrenocortical adenomas in primary aldosteronism
2010 (engelsk)Inngår i: Langenbeck's archives of surgery (Print), ISSN 1435-2443, E-ISSN 1435-2451, Vol. 395, nr 7, s. 963-967Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Purpose: To evaluate whether dexamethasone suppression treatment can improve 11 C-metomidate positron emission tomography (MTO-PET) detection of small adrenocortical adenomas in primary aldosteronism (PA).

Materials and Methods: Eleven patients with proven PA and two patients with non-hyperfunctioning adrenocortical incidentalomas and small adrenocortical tumours observed on CT underwent MTO-PET before and 3 days after administration of oral dexamethasone suppression treatment. Small “hot-spot” regions of interest (ROIs) comprising 4-pixels (SUVhs) and 1-pixel  (SUVmax) were placed in the tumour area with the highest radioactivity concentration and their respective standardised uptake values (SUV) were recorded.

Results: All tumours were detected and categorised as adrenocortical by MTO-PET. SUVhs as well as SUVmax were higher in PA compared to non-functional adenomas. Normal adrenal cortex was suppressed after dexamethasone (p<0.05) but tumour SUV was not significantly decreased after suppression in either PA or non-functional tumours (p>0.05).  However, these changes caused no significant increase in the tumour-to-normal adrenal ratio (p>0.05).

Conclusion: MTO-PET is a highly sensitive method for detecting and categorising even small adrenocortical tumours in PA. In this series dexamethasone-suppressed MTO-PET was ubable to increase the tumour-to-normal-adrenal ratio to further facilitate detection of small adenomas in PA as an alternative to adrenal venous sampling.

Emneord
Metomidate, PET, Primary aldosteronism, Dexamethasone, Adrenal, Suppression
HSV kategori
Identifikatorer
urn:nbn:se:uu:diva-108798 (URN)10.1007/s00423-010-0681-7 (DOI)000283474100020 ()20644954 (PubMedID)
Tilgjengelig fra: 2009-09-29 Laget: 2009-09-29 Sist oppdatert: 2017-12-13bibliografisk kontrollert

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