Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing’s syndrome

Abstract

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.

Cushing’s syndrome due to adrenocorticotropic hormone-secreting metastatic neuroendocrine tumor of unknown primary origin: a case report and literature review

“…The female to male ratio of the 23 patients with available data was 13:10, and the age range of 10 of these patients was 30-55 years [18][19][20][21]25]. The metastases were in the liver and abdominal cavity in the six cases whose metastatic sites were mentioned [4,18,19,25]. However, in our case, the lesions confirming the diagnosis of NEN were in the mediastinal lymph nodes and bones.…”

“…In the 18 FDG-PET/ CT scan, the highest 18 FDG uptake was detected in the right paratra-cheal (SUVmax: 10.69) (d), right hilar and subcarinal lymph nodes (SUVmax: 9.52) (e), and L5 vertebra (black arrow) (SUVmax: 6.11) (f). SUVmax, maximum standardized uptake value of NENs, and the tumor is often localized in the lung or thyroid in cases with ECS [4][5][6]. In UPO NENs, which constitute 13% of metastatic NENs, the most common cause of the functional syndrome is carcinoid syndrome; ACTH secretion can also be seen occasionally [3,7].…”

“…In the literature review, 35 cases of UPO NEN secreting ACTH have been previously reported [4,[18][19][20][21][22][23][24][25][26]. The female to male ratio of the 23 patients with available data was 13:10, and the age range of 10 of these patients was 30-55 years [18][19][20][21]25].…”

Clinical and laboratory characteristics and results of treatment of patients with ACTH-producing neuroendocrine tumors of various localization

“…Сходные данные по соотношению полов получены и в ряде других исследований, однако возраст диагностики заболевания значительно варьировал, составляя [14], 52±15 года по данным I. Lase и соавт. [15] и 56,6±16,3 года в работе J. Paleń-Tytko и соавт. [16].…”

“…Второе место по частоте составили карциноиды тимуса -6,9%. В то время как частота НЭО тимуса в целом совпадает с мировыми данными, где новообразования тимуса с эктопической продукцией АКТГ в среднем встречаются в 4,1-8% случаев [15,16] и в единичных работах в 12,5 [14] и 16% случаев [19], частота НЭО бронхолегочной локализации в нашем исследовании самая высокая среди всех представленных в литературе данных.…”