TY - JOUR
T1 - Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing’s syndrome
AU - Lase, Ieva
AU - Strele, Ieva
AU - Grönberg, Malin
AU - Kozlovacki, Gordana
AU - Welin, Staffan
AU - Janson, Eva Tiensuu
N1 - Funding Information:
Open access funding provided by Uppsala University. This study was funded by the Swedish Cancer Society (grant number CAN 2017/348 [Eva Tiensuu Janson]), the Lions Foundation for Cancer Research at Uppsala University Hospital, and the Selander Foundation and Söderbergs Foundation at Uppsala University.
Publisher Copyright:
© 2020, The Author(s).
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/16
Y1 - 2020/1/16
N2 - Purpose: Ectopic Cushing’s syndrome (ECS) caused by an ACTH secreting neuroendocrine neoplasm (NEN) is a rare and challenging condition. We aimed to detect predictive and prognostic parameters for ECS patients identified from a retrospective, comprehensive cohort of NENs treated at a tertiary referral center. Methods: Medical records of 886 patients with NENs were reviewed. We identified 51 patients with ECS (33 females/18 men); mean age 52 ± 15 years (SD). Clinical parameters including symptoms, biochemical markers, and survival were extracted and further analyzed. Results: The primary tumor was located in the thorax (n = 28) or pancreas (n = 15) or was of unknown primary origin (n = 8). In 30 patients, tumor and ECS were diagnosed simultaneously. In 12 patients, the NEN diagnosis preceded ECS development, with a median time of 43.5 months (range: 9–96), and 10 of these showed radiological tumor progression at ECS diagnosis. Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p = 0.012 (HR 2.4 (95% CI 1.2–4.9)), as did high morning cortisol, p = 0.037 (HR 2.3 (1.0–5.2)), higher tumor grade, p = 0.044 (HR 2.3 (1.0–5.1)), and diabetes, p = 0.050 (HR 2.4 (1.0–6.0)). Conclusions: Multiple hormone secretion, high morning cortisol, higher tumor grade, and diabetes were correlated with shorter OS. Development of ECS in patients with a non-functioning NEN may indicate tumor progression. Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management.
AB - Purpose: Ectopic Cushing’s syndrome (ECS) caused by an ACTH secreting neuroendocrine neoplasm (NEN) is a rare and challenging condition. We aimed to detect predictive and prognostic parameters for ECS patients identified from a retrospective, comprehensive cohort of NENs treated at a tertiary referral center. Methods: Medical records of 886 patients with NENs were reviewed. We identified 51 patients with ECS (33 females/18 men); mean age 52 ± 15 years (SD). Clinical parameters including symptoms, biochemical markers, and survival were extracted and further analyzed. Results: The primary tumor was located in the thorax (n = 28) or pancreas (n = 15) or was of unknown primary origin (n = 8). In 30 patients, tumor and ECS were diagnosed simultaneously. In 12 patients, the NEN diagnosis preceded ECS development, with a median time of 43.5 months (range: 9–96), and 10 of these showed radiological tumor progression at ECS diagnosis. Twenty-one patients had multiple hormone secretion, which correlated with shorter overall survival (OS), p = 0.012 (HR 2.4 (95% CI 1.2–4.9)), as did high morning cortisol, p = 0.037 (HR 2.3 (1.0–5.2)), higher tumor grade, p = 0.044 (HR 2.3 (1.0–5.1)), and diabetes, p = 0.050 (HR 2.4 (1.0–6.0)). Conclusions: Multiple hormone secretion, high morning cortisol, higher tumor grade, and diabetes were correlated with shorter OS. Development of ECS in patients with a non-functioning NEN may indicate tumor progression. Multiple hormone secretion should be considered as a bad prognostic sign in ECS patients and should lead to intensified clinical management.
KW - ACTH
KW - Ectopic Cushing’s syndrome
KW - Hypercortisolism
KW - Hypokalemia
KW - Multiple hormone secretion
KW - Neuroendocrine
UR - http://www.scopus.com/inward/record.url?scp=85078587049&partnerID=8YFLogxK
U2 - 10.1007/s42000-019-00163-z
DO - 10.1007/s42000-019-00163-z
M3 - Article
C2 - 31950464
AN - SCOPUS:85078587049
SN - 1109-3099
VL - 19
SP - 351
EP - 360
JO - Hormones
JF - Hormones
IS - 3
ER -