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      The role of 68Ga-DOTA derivatives PET-CT in patients with ectopic ACTH syndrome

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          Abstract

          Introduction and aim

          Ectopic ACTH secretion (EAS) is mostly secondary to thoracic/abdominal neuroendocrine tumours (NETs) or small cell-lung carcinoma (SCLC). We studied the diagnostic accuracy of CT with 68Ga-Dota derivatives ( 68Ga-SSTR) PET in localizing ACTH-secreting tumor in patients with EAS.

          Materials and methods

          68Ga-SSTR-PET/CT was performed and compared with the nearest enhanced CT in 18 cases (16 primary and 2 recurrent neoplasms). Unspecific, indeterminate and false-positive uptakes were assessed using conventional imaging, follow-up or histology.

          Results

          We diagnosed 13 thoracic (9 primary and 2 recurrent bronchial carcinoids, 2 SCLCs) and 1 abdominal (pancreatic NET) tumors. Eight ACTH-secreting tumors were promptly identified at EAS diagnosis (’overt’, four pulmonary carcinoids with two recurrences and two SCLC); six EAS have been discovered during the subsequent follow-up (’covert’, five bronchial carcinoids and one pancreatic NET). At the time of EAS diagnosis, imaging was able to correctly detect the ACTH-secreting tumour in 8/18 cases (6 new diagnosis and 2 recurrences). During the follow-up, six out of initially ten ‘occult’ cases became ‘covert’. At last available follow-up, CT and 68Ga-SSTR-PET/CT were able to diagnose 11/18 and 12/18 ACTH-secreting tumours, respectively (11/14 and 12/14 considering only overt and covert cases, respectively). Four cases have never been localized by conventional or nuclear imaging (’occult EAS’), despite an average follow-up of 5 years.

          Conclusion

          The 68Ga-SSTR-PET/CT is useful in localizing EAS, especially to enhance positive prediction of the suggestive CT lesions and to detect occult neoplasms.

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          Most cited references26

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          Treatment of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline.

          The objective is to formulate clinical practice guidelines for treating Cushing's syndrome.
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            Somatostatin receptor imaging with 68Ga DOTATATE PET/CT: clinical utility, normal patterns, pearls, and pitfalls in interpretation.

            Gallium 68 ((68)Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotate (DOTATATE, GaTate) positron emission tomography (PET)/computed tomography (CT) is an imaging technique for detecting and characterizing neuroendocrine tumors (NETs). GaTate, a somatostatin analog, has recently been accorded orphan drug status by the U.S. Food and Drug Administration, thereby increasing interest in and availability of this radiotracer. GaTate PET/CT allows whole-body imaging of cell surface expression of somatostatin receptors (SSTRs) and is rapidly evolving as the new imaging standard of reference for the detection and characterization of NETs. The authors discuss the normal appearance at GaTate PET/CT and the utility of this modality in a variety of these tumors, including gastrointestinal, pancreatic, and bronchial NETs as well as pheochromocytoma, paraganglioma, meningioma, and oncogenic osteomalacia. In addition, they discuss potential causes of false-positive findings, including pancreatic uncinate process activity, inflammation, osteoblastic activity, and splenosis. They also highlight the complementary role of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) PET/CT, including the advantages of using both GaTate PET/CT and FDG PET/CT to evaluate sites of well- and poorly differentiated disease. The use of GaTate PET/CT together with FDG PET/CT allows identification of tumor heterogeneity, which provides prognostic information and can be pivotal in guiding biopsy. It also allows optimal patient management, including theranostic application of peptide receptor radionuclide therapy, and the restaging of patients following therapy.
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              Approach to the patient with possible Cushing's syndrome.

              Clinical decision making for patients with suspect hypercortisolism involves a complex diagnostic assessment. Cushing's syndrome remains one of the most challenging endocrine pathologies. Most clinical features overlap with those of common diseases found in the general population, and some patients have an atypical clinical presentation with only isolated symptoms. Recently, several studies have suggested that the prevalence of Cushing's syndrome is higher than previously thought. Therefore, efficient screening tests are needed to identify the few uncovered patients also among unselected high-risk ambulatory patients with disorders potentially related to cortisol excess. The recommended diagnostic tests are 24-h urinary free cortisol, 1-mg overnight dexamethasone suppression test, and late-night salivary cortisol. Once the diagnosis of Cushing's syndrome is established, the next step is the measurement of plasma ACTH. Then, dynamic test and appropriate imaging procedures are the most useful noninvasive investigations for the differential diagnosis. Patients with Cushing's disease are generally responsive to the CRH test and to high-dose glucocorticoid feedback. Bilateral inferior petrosal sinus sampling is considered the gold standard for establishing the origin of ACTH secretion, and it is recommended in patients with ACTH-dependent Cushing's syndrome whose clinical, biochemical, or radiological studies are discordant or equivocal. The present clinical case shows that even if rare, the ectopic ACTH secretion should be considered also in those cases where the pretest probability is low. The management of Cushing's syndrome depends on the exact knowledge of its various causes, paying attention to the many potential diagnostic pitfalls. The choice of test, the modality of specimen collection (blood, urine, and saliva), the quality of measurement (assay methodology and standardization), and close dialogue among endocrinologists, chemical pathologists, and neuroradiologists are key factors for optimal care of patients.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                April 2020
                26 March 2020
                : 9
                : 4
                : 337-345
                Affiliations
                [1 ]Endocrinology Unit , Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy
                [2 ]Department of Neuroscience DNS , University of Padova, Padova, Italy
                [3 ]Nuclear Medicine Unit , Department of Medicine – DIMED, University-Hospital of Padova, Padova, Italy
                [4 ]Padova Neuroscience Center PNC , University of Padova, Padova, Italy
                [5 ]Nuclear Medicine Unit , Castelfranco Veneto, Italy
                [6 ]Department of Mathematics ‘Tullio Levi-Civita’ DM , University of Padova, Padova, Italy
                [7 ]Radiology Unit , Department of Medicine DIMED, University-Hospital of Padova, Padova, Italy
                [8 ]Nuclear Medicine Unit , Reggio Emilia, Italy
                [9 ]Radiology Department , University-Hospital of Padova, Padova, Italy
                [10 ]Thoracic Surgery Unit , Department of Cardiac, Thoracic and Vascular Sciences, University Hospital of Padova, Padova, Italy
                Author notes
                Correspondence should be addressed to F Ceccato: filippo.ceccato@ 123456unipd.it
                Article
                EC-20-0089
                10.1530/EC-20-0089
                7219142
                32213660
                e033df37-c898-4e9c-93e6-55217bb4bff8
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 13 March 2020
                : 26 March 2020
                Categories
                Research

                ectopic cushing’s syndrome,diagnosis,computed tomography,68ga-sstr-pet/ct

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