Keywords
How to Cite
Abstract
The ectopic ACTH syndrome (EAS) remains one of the most difficult for differential diagnosis in endocrinology. EAS is the result of unregulated expression and secretion of ACTH predominantly by neuroendocrine tumors (NETs) of various degrees of histological differentiation, which causes significant cortisol secretion from the adrenal cortex and the specific manifestations of Cushing's syndrome (CS). To analyze data on this issue, publications were searched in PubMed, Scopus, Web of Science, Google, and Google Scholar (2000-2023). During this period, more than 300 publications were identified on ACTH-secreting tumors of various localization, accompanied by SC. At the end of the last century, when researchers paid attention to the sudden onset of clinical signs of severe hypercorticism, associated with the presence of aggressive malignant neoplasms, the latter were predominantly represented by small cell lung cancer. Thanks to the improvement in imaging techniques, the spectrum of ACTH-secreting tumors has expanded over time. There are some difficulties in differentiating EAS from Cushing's disease, since ACTH-secreting NETs are oftenмsmall, and difficult to detect, and the classic symptoms andмbiochemical characteristics of hypercorticism are similar or evenмidentical to those of corticotrophic pituitary tumors. That is why EASмis considered an endocrine emergency that requiresм an emergency response both in terms of diagnosis and treatment. They emphasize the importance of conducting a thorough examination of patients, taking into account even minor clinical manifestations of the disease, the results of biochemical tests in dynamics, and evaluating the results of multimodal imaging when searching for the localization of a neoplasm with a deep understanding of the existing caveats regarding each method. Despite the achievement of diagnosis, up to 20% of tumors remain undiagnosed, which is a challenge for the clinical endocrinologist, as in some cases the tumor cannot be detected after long-term observation or even during autopsy. The article discusses the epidemiology of EAS, possible mechanisms of ACTH expression by tumor cells, the complexity of diagnosis and characteristic features of EAS depending on the localization and nature of ectopic sources of ACTH, as well as a description of the
clinical case.
References
2. Toivanen S, Leijon H, Arola A, Soinio M, Hämäläinen PO, Metso S, et al. Characteristics and outcomes of the Finnish ectopic ACTH syndrome cohort. Endocrine. 2021;74(2):387-95. doi: 10.1007/s12020-021-02768-0.
3. Isidori AM, Kaltsas GA, Pozza C, Frajese V, Newell-Price J, Reznek RH, et al. The ectopic adrenocorticotropin syndrome: clinical features, diagnosis, management, and long-term follow-up. J Clin Endocrinol Metab. 2006;91(2):371-7. doi: 10.1210/jc.2005-1542.
4. Attri B, Goyal A, Kalaivani M, Kandasamy D, Gupta Y, Agarwal S, et al. Clinical profile and treatment outcomes of patients with ectopic ACTH syndrome compared to Cushing disease: a single-center experience. Endocrine. 2023;80(2):408-18. doi: 10.1007/s12020-022-03298-z.
5. Walia R, Dutta A, Gupta N, Bhansali A, Pivonello R, Ahuja CK, et al. Etiology, sex-, and tumor size-based differences in adrenocorticotropin-dependent Cushing syndrome. Endocr Pract. 2021;27(5):471-7. doi: 10.1016/j.eprac.2020.11.014.
6. Espinosa-de-Los-Monteros AL, Ramírez-Rentería C, Mercado M. Clinical heterogeneity of ectopic ACTH syndrome: a longterm follow-up study. Endocr Pract. 2020;26(12):1435-41. doi: 10.4158/EP-2020-0368.
7. La Rosa S, Volante M, Uccella S, Maragliano R, Rapa I, Rotolo N, et al. ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature. Virchows Arch. 2019;475(5):587-97. doi: 10.1007/s00428-019-02612-x.
8. Landry JP, Clemente-Gutierrez U, Pieterman CRC, Chiang YJ, Waguespack SG, Jimenez C, et al. Management of adrenocorticotropic hormone-secreting neuroendocrine tumors and the role of bilateral adrenalectomy in ectopic Cushing syndrome. Surgery. 2022;172(2):559-66. doi: 10.1016/j.surg.2022.03.014.
9. Paleń-Tytko JE, Przybylik-Mazurek EM, Rzepka EJ, Pach DM, Sowa-Staszczak AS, Gilis-Januszewska A, et al. Ectopic ACTH syndrome of different origin-Diagnostic approach and clinical outcome. Experience of one Clinical Centre. PLoS One. 2020;15(11):e0242679. doi: 10.1371/journal.pone.0242679.
10. Zhou X, Hang J, Che J, Chen Z, Qiu W, Ren J, et al. Surgical treatment of ectopic adrenocorticotropic hormone syndrome with intra-thoracic tumor. J Thorac Dis. 2016;8(5):888-93. doi: 10.21037/jtd.2016.03.54.
11. Aniszewski JP, Young WF Jr, Thompson GB, Grant CS, van Heerden JA. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion. World J Surg. 2001;25(7):934-40. doi: 10.1007/s00268-001-0032-5.
12. Davi’s MV, Cosaro E, Piacentini S, Reimondo G, Albiger N, Arnaldi G, et al. Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study. Eur J Endocrinol. 2017;176(4):453-61. doi: 10.1530/EJE-16-0809.
13. Doi M, Sugiyama T, Izumiyama H, Yoshimoto T, Hirata Y. Clinical features and management of ectopic ACTH syndrome at a single institute in Japan. Endocr J. 2010;57(12):1061-9. doi: 10.1507/endocrj.k10e-265.
14. Araujo Castro M, Palacios García N, Aller Pardo J, Izquierdo Alvarez C, Armengod Grao L, Estrada García J. Ectopic Cushing syndrome: report of 9 cases. Endocrinol Diabetes Nutr (Engl Ed). 2018;65(5):255-64. English, Spanish. doi: 10.1016/j.endinu.2018.02.001.
15. Karageorgiadis AS, Papadakis GZ, Biro J, Keil MF, Lyssikatos C, Quezado MM, et al. Ectopic adrenocorticotropic hormone and corticotropin-releasing hormone co-secreting tumors in children and adolescents causing cushing syndrome: a diagnostic dilemma and how to solve it. J Clin Endocrinol Metab. 2015;100(1):141-8. doi: 10.1210/jc.2014-2945.