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. 2025 Sep 22;14(9):e250411.
doi: 10.1530/EC-25-0411. Print 2025 Sep 1.

Long-term outcomes and survival predictors in patients with ectopic ACTH syndrome: data from a retrospective cohort study

Zhanna Belaya  1 , Liudmila Rozhinskaya  1 , Olga Golounina  1 , Alexander Solodovnikov  2 , Evgeniya Marova  1 , Svetlana Arapova  1 , Michail Pikunov  3 , Alla Markovich  4 , Elizaveta Mamedova  1 , Elena Przhialkovskaya  1 , Ekaterina Pigarova  1 , Valentin Fadeev  5 , Nikolay Kuznetsov  1 , Ivan Sitkin  1 , Larisa Dzeranova  1 , Alexander Lutsenko  1 , Natalia Mokrysheva  1 , Ivan Dedov  1 , Galina Melnichenko  1
Affiliations

Long-term outcomes and survival predictors in patients with ectopic ACTH syndrome: data from a retrospective cohort study

Zhanna Belaya et al. Endocr Connect. .

Abstract

Background: Ectopic ACTH syndrome (EAS) is caused by non-pituitary neuroendocrine tumor (NET) that produces adrenocorticotropic hormone (ACTH).

Objective: To identify survival predictors and to analyze long-term outcomes in patients with EAS.

Methods: Medical records of patients with verified EAS between 1990 and 2024 were analyzed to obtain the initial clinical and biochemical data along with subsequent interventions and survival outcomes.

Results: The study included 173 patients (107 women and 66 men), with a median (Q25-Q75) age of 42 years (29; 55). The median follow-up period was 54 months (16; 99) with a maximum of 402 months. Over the observation period, death was registered in 50 (28.9%) cases. The overall 3- and 5-year survival rates were 77 and 70%, respectively. Multivariable analysis revealed the following negative predictive factors for survival: age at diagnosis ≥51 years (hazard ratio (HR) 3.53; 95% confidence interval (CI): 1.67-7.5; P = 0.001), presence of metastases (HR 2.93; 95% CI: 1.35-6.32; P = 0.006), and active hypercortisolism (HR 5.58; 95% CI 1.62-19.24; P = 0.006) along with late night salivary cortisol levels (LNSC) above 130 nmol/L (HR 2.81; 95% CI: 1.30-6.07; P = 0.009).

Conclusion: Active hypercortisolism, high LNSC, distant metastases and older age at diagnosis are factors associated with mortality in EAS. As severity of hypercortisolism is the main targetable factors, it should be the focus of intervention and further studies aimed at improving outcomes.

Keywords: ectopic ACTH syndrome; hypercortisolism; mortality; neuroendocrine tumor; survival analyses.

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Conflict of interest statement

The authors declare that the work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Overall survival by patient age upon diagnosis. Survival probabilities were estimated employing the Kaplan–Meier method. Survival curves were compared employing the log-rank test.
Figure 2
Figure 2
Overall survival by the presence of metastases. Survival probabilities were estimated using the Kaplan–Meier method. Survival curves were compared employing the log-rank test.
Figure 3
Figure 3
Overall survival by active hypercortisolism and late-night salivary cortisol levels. (A) Hypercortisolism and (B) late-night salivary cortisol. Survival probabilities were estimated employing the Kaplan–Meier method. Survival curves were compared employing the log-rank test.
See this image and copyright information in PMC

References

    1. Lacroix A, Feelders RA, Stratakis CA, et al. Cushing syndrome. Lancet 2015. 386 913–927. ( 10.1016/S0140-6736(14)61375-1) - DOI - PubMed
    1. Feelders R, Sharma S & Nieman L. Cushing syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015. 7 281. ( 10.2147/CLEP.S44336) - DOI - PMC - PubMed
    1. Toivanen S, Leijon H, Arola A, et al. Characteristics and outcomes of the finnish ectopic ACTH syndrome cohort. Endocrine 2021. 74 387–395. ( 10.1007/s12020-021-02768-0) - DOI - PubMed
    1. Brown WH. A case of pluriglandular syndrome: “diabetes of bearded women.”. Lancet 1928. 212 1022–1023. ( 10.1016/S0140-6736(00)84800-X) - DOI
    1. Ma Y, Aitelli C, Dobson RW, et al. Ectopic adrenocorticotropic hormone syndrome: a diagnostic challenge and review of the literature. Baylor Univ Med Cent Proc 2010. 23 426–428. ( 10.1080/08998280.2010.11928663) - DOI - PMC - PubMed

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