Multiple hormone secretion may indicate worse prognosis in patients with ectopic Cushing\u2019s syndrome

Ieva Lase,Gordana Kozlovacki,Eva Tiensuu Janson,Ieva Strele,Staffan Welin,Malin Grönberg

doi:10.1007/s42000-019-00163-z

Ieva Lase, Gordana Kozlovacki + Show 4 more

Open Access

https://doi.org/10.1007/s42000-019-00163-z

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Abstract

PurposeEctopic 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.MethodsMedical 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.ResultsThe 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)).ConclusionsMultiple 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.

Highlights

High levels of plasma cortisol may be due to several different medical disorders but they almost always lead to a severe health condition in the patient
There were no patients with Ectopic Cushing’s syndrome (ECS) due to medullary thyroid carcinoma identified in our cohort
Among the eight patients with ECS and neuroendocrine neoplasm (NEN) of unknown primary origin, three patients had liver metastases at diagnosis, but the primary tumor was never found, while in five patients, a tumor could not be found despite extensive workup, including octreotide scintigraphy and/or positron emission tomography

Summary

Introduction

High levels of plasma cortisol may be due to several different medical disorders but they almost always lead to a severe health condition in the patient. The clinical picture of ectopic Cushing’s syndrome (ECS) can be the same as in Cushing’ s disease, but the rapid onset, severity, and progress of symptoms may suggest an ectopic source [2]. The clinical signs and symptoms include hypertension, high levels of blood glucose (often manifest diabetes mellitus), hypokalemia and metabolic alkalosis, and psychopathology and neurocognitive disorders, among many other manifestations. The most well-known tumor responsible for ectopic ACTH production is small cell lung carcinoma (SCLC), and among SCLCs, 3.5–50% is reported to produce ACTH [2]. The reported prevalence range of ECS in patients with SCLC is very wide and probably depends on referral patterns of the patients to specialized clinics as well as small cohort sizes

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