Elena Varlamov1,2,3, José Miguel Hinojosa-Amaya2,3,4, Madeleine Stack3, Maria Fleseriu5,6,7. 1. Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, L607, Portland, OR, USA. 2. Department of Neurological Surgery, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA. 3. Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA. 4. Endocrinology Division, Department of Medicine, Hospital Universitario "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico. 5. Department of Medicine, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health & Science University, 3181 S.W. Sam Jackson Park Road, L607, Portland, OR, USA. fleseriu@ohsu.edu. 6. Department of Neurological Surgery, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA. fleseriu@ohsu.edu. 7. Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, USA. fleseriu@ohsu.edu.
Abstract
PURPOSE: Tumors causing ectopic Cushing's syndrome (ECS) are often not visible with conventional imaging. Gallium-68-DOTATATE, DOTATOC, and DOTANOC positron emission tomography/computed tomography (68Ga-SSTR PET/CT) reportedly exhibits greater sensitivity in identifying an ECS source, however, evidence is limited to mainly case reports and a few small retrospective studies. Previous systematic ECS imaging review has shown 68Ga-SSTR PET/CT sensitivity is similar to CT (81.8%) in histologically-proven cases and is 100% in covert-cases, however, the number of patients was small and no occult cases were reported. METHODS: We performed a systematic literature review of 68Ga-SSTR PET/CT use in ECS patients. We also report 6 consecutive patients with confirmed active and occult ECS who underwent 68Ga-DOTATATE PET/CT and were followed at our institution between 2014 and 2019. RESULTS: We identified 33 articles (23 case-reports, 4 case-series, 5 retrospective studies and 1 prospective study) detailing 68Ga-SSTR PET/CT in 69 ECS patients. Overall 68Ga-SSTR PET/CT sensitivity was 64.0%, while in histologically confirmed cases (67 lesions), sensitivity was 76.1%. There were two false-positives cases, both in the adrenal glands. In covert cases, 68Ga-SSTR PET/CT identified 50% of lesions. There were ten occult cases where all imaging failed to identify an adrenocorticotropic hormone source; source remains unknown. In our case series, 68Ga-DOTATATE PET/CT showed decreased uptake in pancreatic neuroendocrine tumor in one patient and did not help identify an ECS source in 5 patients. CONCLUSION: Both this systematic literature review, the largest to date, and our single- center experience demonstrate a lower than previously reported 68Ga-SSTR PET/CT sensitivity for ECS, especially in occult lesions. We suggest that the data on 68Ga-SSTR PET/CT in ECS is subject to publication bias, and false-negatives are likely underreported; it's diagnostic value for ECS needs further study.
PURPOSE:Tumors causing ectopic Cushing's syndrome (ECS) are often not visible with conventional imaging. Gallium-68-DOTATATE, DOTATOC, and DOTANOC positron emission tomography/computed tomography (68Ga-SSTR PET/CT) reportedly exhibits greater sensitivity in identifying an ECS source, however, evidence is limited to mainly case reports and a few small retrospective studies. Previous systematic ECS imaging review has shown 68Ga-SSTR PET/CT sensitivity is similar to CT (81.8%) in histologically-proven cases and is 100% in covert-cases, however, the number of patients was small and no occult cases were reported. METHODS: We performed a systematic literature review of 68Ga-SSTR PET/CT use in ECS patients. We also report 6 consecutive patients with confirmed active and occult ECS who underwent 68Ga-DOTATATE PET/CT and were followed at our institution between 2014 and 2019. RESULTS: We identified 33 articles (23 case-reports, 4 case-series, 5 retrospective studies and 1 prospective study) detailing 68Ga-SSTR PET/CT in 69 ECS patients. Overall 68Ga-SSTR PET/CT sensitivity was 64.0%, while in histologically confirmed cases (67 lesions), sensitivity was 76.1%. There were two false-positives cases, both in the adrenal glands. In covert cases, 68Ga-SSTR PET/CT identified 50% of lesions. There were ten occult cases where all imaging failed to identify an adrenocorticotropic hormone source; source remains unknown. In our case series, 68Ga-DOTATATE PET/CT showed decreased uptake in pancreatic neuroendocrine tumor in one patient and did not help identify an ECS source in 5 patients. CONCLUSION: Both this systematic literature review, the largest to date, and our single- center experience demonstrate a lower than previously reported 68Ga-SSTR PET/CT sensitivity for ECS, especially in occult lesions. We suggest that the data on 68Ga-SSTR PET/CT in ECS is subject to publication bias, and false-negatives are likely underreported; it's diagnostic value for ECS needs further study.
Authors: Andrea M Isidori; Gregory A Kaltsas; Carlotta Pozza; Vanni Frajese; John Newell-Price; Rodney H Reznek; Paul J Jenkins; John P Monson; Ashley B Grossman; G Michael Besser Journal: J Clin Endocrinol Metab Date: 2005-11-22 Impact factor: 5.958
Authors: Shamim Ejaz; Rena Vassilopoulou-Sellin; Naifa L Busaidy; Mimi I Hu; Steven G Waguespack; Camilo Jimenez; Anita K Ying; Maria Cabanillas; Maher Abbara; Mouhammed Amir Habra Journal: Cancer Date: 2011-03-15 Impact factor: 6.860
Authors: Ioannis Ilias; David J Torpy; Karel Pacak; Nancy Mullen; Robert A Wesley; Lynnette K Nieman Journal: J Clin Endocrinol Metab Date: 2005-05-24 Impact factor: 5.958
Authors: C de Bruin; R A Feelders; A M Waaijers; P M van Koetsveld; D M Sprij-Mooij; S W J Lamberts; L J Hofland Journal: J Mol Endocrinol Date: 2008-10-13 Impact factor: 5.098
Authors: Brooke Swearingen; Laurence Katznelson; Karen Miller; Steven Grinspoon; Arthur Waltman; David J Dorer; Anne Klibanski; Beverly M K Biller Journal: J Clin Endocrinol Metab Date: 2004-08 Impact factor: 5.958
Authors: Maria Fleseriu; Richard Auchus; Irina Bancos; Anat Ben-Shlomo; Jerome Bertherat; Nienke R Biermasz; Cesar L Boguszewski; Marcello D Bronstein; Michael Buchfelder; John D Carmichael; Felipe F Casanueva; Frederic Castinetti; Philippe Chanson; James Findling; Mônica Gadelha; Eliza B Geer; Andrea Giustina; Ashley Grossman; Mark Gurnell; Ken Ho; Adriana G Ioachimescu; Ursula B Kaiser; Niki Karavitaki; Laurence Katznelson; Daniel F Kelly; André Lacroix; Ann McCormack; Shlomo Melmed; Mark Molitch; Pietro Mortini; John Newell-Price; Lynnette Nieman; Alberto M Pereira; Stephan Petersenn; Rosario Pivonello; Hershel Raff; Martin Reincke; Roberto Salvatori; Carla Scaroni; Ilan Shimon; Constantine A Stratakis; Brooke Swearingen; Antoine Tabarin; Yutaka Takahashi; Marily Theodoropoulou; Stylianos Tsagarakis; Elena Valassi; Elena V Varlamov; Greisa Vila; John Wass; Susan M Webb; Maria C Zatelli; Beverly M K Biller Journal: Lancet Diabetes Endocrinol Date: 2021-10-20 Impact factor: 32.069