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. 2021 Nov;74(2):387-395.
doi: 10.1007/s12020-021-02768-0. Epub 2021 May 25.

Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort

Sanna Toivanen  1   2 , Helena Leijon  3 , Aura Arola  4 , Minna Soinio  4 , Päivi O Hämäläinen  5 , Saara Metso  5 , Otto Knutar  6 , Minna Koivikko  7 , Tapani Ebeling  7 , Leena Moilanen  8 , Leena Norvio  2 , Marjo Tamminen  9 , Päivi Rautiainen  10 , Satu Vehkavaara  1 , Eeva Ryhänen  1 , Tuula Pekkarinen  1 , Niina Matikainen  1 , Timo Sane  1 , Camilla Schalin-Jäntti  11
Affiliations

Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort

Sanna Toivanen et al. Endocrine. 2021 Nov.

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.

Keywords: Cushing’s syndrome; Ectopic ACTH syndrome; Hypercortisolism; Neuroendocrine carcinoma; Neuroendocrine tumor.

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