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.

中文翻译：

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多激素分泌可能表明异位库欣综合症患者的预后较差。

目的

由分泌ACTH的神经内分泌肿瘤（NEN）引起的异位库欣综合症（ECS）是一种罕见且具有挑战性的疾病。我们的目的是为从三级转诊中心接受治疗的NEN回顾性综合队列中确定的ECS患者检测预测和预后参数。

方法

审查了886名NEN患者的病历。我们确定了51名ECS患者（33名女性/ 18名男性）；平均年龄52±15岁（SD）。提取并进一步分析包括症状，生化标志物和生存期在内的临床参数。

结果

原发肿瘤位于胸部（n  = 28）或胰腺（n  = 15）或原发灶未知（n  = 8）。在30例患者中，肿瘤和ECS同时被诊断。在12例患者中，NEN诊断先于ECS发展，中位时间为43.5个月（范围：9–96），其中10例在ECS诊断时显示出放射性肿瘤进展。21名患者具有多种激素分泌，这与较短的总生存期（OS）相关，p  = 0.012（HR 2.4（95％CI 1.2–4.9）），早晨皮质醇水平较高，p  = 0.037（HR 2.3（1.0–9） 5.2）），较高的肿瘤等级（p  = 0.044（HR 2.3（1.0–5.1））和糖尿病，p  = 0.050（HR 2.4（1.0–6.0））。

结论

多种激素分泌，早上皮质醇升高，肿瘤等级较高和糖尿病与较短的OS相关。NEN无效的患者出现ECS可能表明肿瘤进展。多种激素分泌应被视为ECS患者的不良预后体征，并应导致加强临床管理。