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Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort

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Abstract

Purpose

Ectopic ACTH syndrome (EAS) is rare. We established a national cohort to increase awareness and address unmet needs.

Methods

The Finnish national EAS cohort includes 60 patients diagnosed in 1997–2016. We assessed clinical features, diagnostic work-ups, treatments, incidence, and outcomes of subgroups occult tumor (OT), well-differentiated neuroendocrine tumor G1/G2 (NETG1/G2) and NET G3/neuroendocrine carcinoma (NETG3/NEC).

Results

The distribution of OT, NETG1/G2, and NETG3/NEC was 10 (17%), 20 (33%), and 30 (50%), respectively; and median follow-up 22 months (0–249). Annual incidence (0.20–0.93 per million inhabitants) and tumor subgroups (OT vs. NEC) varied across the country. The longest diagnostic delay from EAS onset to radiological tumor identification was 48 months. In NET/NEC, 6/50 (12%) were diagnosed 1–24 years before EAS onset. Osteoporotic fractures (32%) and severe infections (55%) were common. The CRH stimulation test accurately diagnosed EAS in 25/31 (81%). Metyrapone (≤6 g daily, prescribed in 88%) was well tolerated. In NETG1/G2, 13/20 (65%) underwent curative resection of the primary tumor; four experienced recurrence within 2–12 years. In OT, 70% underwent bilateral adrenalectomy. Five-year overall survival in OT, NETG1/G2, and NETG3/NEC was 90%, 55%, and 0%, respectively (P < 0.001). Morning cortisol, hypokalemia, infections, metastatic disease, and acute onset were negative, whereas resection of the primary tumor and bilateral adrenalectomy were positive predictors of survival.

Conclusions

NET/NEC may precede EAS onset by several years. In NETG1/G2, recurrences may occur > 10 years after successful primary surgery. Tumor subgroup (OT, NETG1/G2, NEC) was an independent predictor of survival.

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Acknowledgements

This study was supported by grants from the Helsinki University Hospital Research Funds (TYH2018223, TYH2019254) and Finska Läkaresällskapet (not numbered) (to C.S.-J.).

Author information

Authors and Affiliations

  1. Endocrinology, Abdominal Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

    Sanna Toivanen, Satu Vehkavaara, Eeva Ryhänen, Tuula Pekkarinen, Niina Matikainen, Timo Sane & Camilla Schalin-Jäntti

  2. Divison of Endocrinology, Helsinki University Hospital, Hyvinkää, Finland

    Sanna Toivanen & Leena Norvio

  3. Department of Pathology, University of Helsinki and HUSLAB, Helsinki University Hospital, Helsinki, Finland

    Helena Leijon

  4. Department of Endocrinology, Turku University Hospital and University of Turku, Turku, Finland

    Aura Arola & Minna Soinio

  5. Department of Internal Medicine and Tampere University, Faculty of Medicine and Health Technology, Tampere University Hospital, Tampere, Finland

    Päivi O. Hämäläinen & Saara Metso

  6. Department of Internal Medicine, Vaasa Central Hospital, Vaasa, Finland

    Otto Knutar

  7. Department of Internal Medicine, Oulu University Hospital and University of Oulu, Oulu, Finland

    Minna Koivikko & Tapani Ebeling

  8. Department of Medicine, Kuopio University Hospital, Kuopio, Finland

    Leena Moilanen

  9. Department of Internal Medicine, Central Hospital of Kymenlaakso, Kotka, Finland

    Marjo Tamminen

  10. Department of Internal Medicine, Joint Muncipal Authority for North Karelia Social and Health Services (Siun sote), Joensuu, Finland

    Päivi Rautiainen

Authors
  1. Sanna Toivanen
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  2. Helena Leijon
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  3. Aura Arola
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  4. Minna Soinio
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  14. Satu Vehkavaara
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  15. Eeva Ryhänen
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  16. Tuula Pekkarinen
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  17. Niina Matikainen
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  18. Timo Sane
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  19. Camilla Schalin-Jäntti
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Contributions

All authors contributed sufficiently (data collection, approving final manuscript as the minimum) to be listed as authors.

Corresponding author

Correspondence to Camilla Schalin-Jäntti.

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Conflict of interest

The authors declare no conflicts of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study was conducted in accordance with the Declaration of Helsinki. Authorization to perform this study without individual consent was granted by the Ethical Committee of the Helsinki University Central Hospital (HUS 2024/2016) and the Review Boards of the individual hospitals.

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Toivanen, S., Leijon, H., Arola, A. et al. Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort. Endocrine 74, 387–395 (2021). https://doi.org/10.1007/s12020-021-02768-0

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