Sanna Toivanen1,2, Helena Leijon3, Aura Arola4, Minna Soinio4, Päivi O Hämäläinen5, Saara Metso5, Otto Knutar6, Minna Koivikko7, Tapani Ebeling7, Leena Moilanen8, Leena Norvio2, Marjo Tamminen9, Päivi Rautiainen10, Satu Vehkavaara1, Eeva Ryhänen1, Tuula Pekkarinen1, Niina Matikainen1, Timo Sane1, Camilla Schalin-Jäntti11. 1. Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. 2. Divison of Endocrinology, Helsinki University Hospital, Hyvinkää, Finland. 3. Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland. 4. Department of Endocrinology, Turku University Hospital and University of Turku, Turku, Finland. 5. Department of Internal Medicine and Tampere University, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere, Finland. 6. Department of Internal Medicine, Vaasa Central Hospital, Vaasa, Finland. 7. Department of Internal Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland. 8. Department of Medicine, Kuopio University Hospital, Kuopio, Finland. 9. Department of Internal Medicine, Central Hospital of Kymenlaakso, Kotka, Finland. 10. Department of Internal Medicine, Joint Muncipal Authority for North Karelia Social and Health Services (Siun sote), Joensuu, Finland. 11. Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland. camilla.schalin-jantti@hus.fi.
Abstract
PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.
PURPOSE: Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs. METHODS: The Finnish national EAS cohort includes 60 patients diagnosed in 1997-2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC). RESULTS: The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0-249). Annual incidence (0.20-0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1-24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2-12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival. CONCLUSIONS: NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.
Authors: German Rubinstein; Andrea Osswald; Eva Hoster; Marco Losa; Atanaska Elenkova; Sabina Zacharieva; Márcio Carlos Machado; Felicia Alexandra Hanzu; Stephanie Zopp; Katrin Ritzel; Anna Riester; Leah Theresa Braun; Ilonka Kreitschmann-Andermahr; Helen L Storr; Prachi Bansal; María-José Barahona; Elisa Cosaro; Sema Ciftci Dogansen; Philip C Johnston; Ricardo Santos de Oliveira; Christian Raftopoulos; Carla Scaroni; Elena Valassi; Steven J A van der Werff; Jochen Schopohl; Felix Beuschlein; Martin Reincke Journal: J Clin Endocrinol Metab Date: 2020-03-01 Impact factor: 5.958