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MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome due to ectopic ACTH secretion: an expert operational opinion
Abstract
Ectopic ACTH syndrome (EAS) is rare but is frequently a severe condition because of the intensity of the hypercortisolism that may be dissociated from the tumoral condition. EAS should often be considered as an endocrine emergency requiring an emergency response both in terms of diagnostic procedures and therapeutic interventions. Patient management is complex and necessitates dual skills, in the diagnosis and treatment of CS and in the specific management of neuroendocrine tumors (NET). Therefore, initial management should be performed ideally by experienced endocrinology teams in collaboration with specialized hormonal laboratory, modern imaging platforms and intensive care units. Diagnostic procedures vary according to the endocrine and tumoral contexts but should be reduced to a minimum in intense hypercortisolism. Preventive and curative treatments of cortisol-induced comorbidities, non-specific management of hypercortisolism and etiological treatments should be considered simultaneously. Therapeutic strategies vary according to (1.) the intensity of hypercortisolism, the general condition of the patient and associated comorbidities and (2.) the tumoral status, ranging from resectable ACTH secreting tumors to non-resectable metastatic endocrine tumors or occult tumors. The ideal treatment is complete excision of the ACTH-secreting tumor that can be performed rapidly or after preoperative preparation using cortisol-lowering drugs. When this is not possible, the therapeutic strategy should be discussed by a multidisciplinary experienced team in a personalized perspective and include variable combinations of pharmacological agents, bilateral adrenalectomy and non-specific tumoral interventions. Here we discuss the diagnosis and therapeutic strategies including the modern, currently available tools and emphasize on the operational effectiveness of care.
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“Second-line tests include functional imaging using 68Ga-PET/CT or 18FDG PET/CT scans, which can be used to detect occult tumors, reinforce tumors seen on CT scan as being neuroendocrine, or contribute to the workup of metastatic tumors (9, 81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“Desmopressin testing can also be used because type 2 vasopressin receptors, which are generally absent in normal pituitary corticotrophs, have found to be expressed in corticotroph adenomas.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“Therefore, an increase in plasma ACTH and cortisol can be observed after injection of desmopressin in patients with Cushing disease (81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“Dynamic testing with high-dose DST, CRH test, and desmopressin testing can also be used to help differentiate between Cushing disease and EAS (9, 81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“On the other hand, an absence of both ACTH and cortisol is expected in patients with EAS, although false-positive results can be seen as EAS tumors may express type 3 vasopressin receptors (9, 74, 81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“Patients with EAS are typically unresponsive although some tumors, in particular bronchial carcinoids can express CRH receptors (9, 74, 81, 82).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“The CRH test is useful because corticotroph pituitary adenomas express CRH receptors and associated downstream cell-signaling pathway molecules, thereby responding to CRH by releasing excess ACTH compared with ectopic ACTH-secreting tumors (81).”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
In the citing paper
“Therefore, most but not all patients with Cushing disease will have an increase in plasma ACTH by more than 50% and cortisol concentrations by more than 20% after CRH stimulation.”
From Approach to the Patient: Diagnosis of Cushing Syndrome (2022) · cites this paper as [81]
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García, C. J., Sirera, P. S., Quesada, M. E. T., Bueno, V. G., & Guerra, R. A. (2022) · Advances in Laboratory Medicine / Avances en Medicina de Laboratorio · doi:10.1515/almed-2022-0081
Relevance of inferior petrosal sinus sampling in the diagnosis of Cushing’s syndrome: a case report
García, C. J., Sirera, P. S., Quesada, M. E. T., Bueno, V. G., & Guerra, R. A. (2022) · Advances in Laboratory Medicine / Avances en Medicina de Laboratorio · doi:10.1515/almed-2022-0104
ACTH-Producing Pancreatic Tumor
Uccella, S. (2022) · Encyclopedia of pathology · doi:10.1007/978-3-030-62345-6_5296
Furnica, R. M., NACHIT, M., Collard, A., Cornélis, F., Alexopoulou, O., & Maiter, D. M. (2023) · Research Square · doi:10.21203/rs.3.rs-2674724/v1
A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz
Fernandes, A. P., Falcão, L., & Raimundo, M. R. (2023) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2022.11.005
Hydrosaline Alterations in Cushing Disease
Alcubierre, D. D., Sbardella, E., & Isidori, A. M. (2023) · Endocrinology · doi:10.1007/978-3-030-44628-4_15-1
A clinical case of ectopic ACTH syndrome: diagnostic difficulties
Kholupko, N. V., Kholupko, E. N., Navmenova, Y. L., Wisham, M., Филюстин, А. Е., Коротаев, А. В., Kholupko, E. N., Zhuravlev, V. A., & Русаленко, М. Г. (2023) · Medical and Biological Problems of Life Activity · doi:10.58708/2074-2088.2023-1(29)-99-104
Ohba, D., Okamoto, Y., Miyamoto, U., Takeda, Y., Terazaki, Y., & Hiratsuka, M. (2023) · Haigan · doi:10.2482/haigan.63.182
Estado hiperglucémico hiperosmolar secundario a síndrome de Cushing paraneoplásico
Jiménez-García, N., Guardabrazo, C. F., & del Pino, J. L. (2023) · Medicina Clínica · doi:10.1016/j.medcli.2023.06.018
Lee, K., Kaltsas, G., & Mukherjee, J. J. (2023) · Wiley eBooks · doi:10.1002/9781119876007.ch103
Ashraf, S., Parveen, S., Ashraf, S., Batool, U., Sultana, M., Ishaque, U., Shafqat, Z., Shabbir, S., Riaz, Z., & Faiz, Z. (2023) · BioScientific Review · doi:10.32350/bsr.52.04
Ectopic Adrenocorticotropic Hormone-Producing Metastatic Gastrinoma: A Case Report
Tamhane, S. U., Menon, L., Edem, D., Sharma, P., & Maradana, J. (2023) · Cureus · doi:10.7759/cureus.45329
Espinosa-Cárdenas, E., García-Sáenz, M. R., Espinosa-de-los-Monteros, A. L., & Sosa, E. (2023) · Archives of Medical Research · doi:10.1016/j.arcmed.2023.102882
Hyperglycemic hyperosmolar state secondary to paraneoplastic Cushing's syndrome
Jiménez-García, N., Guardabrazo, C. F., & del Pino, J. L. (2023) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2023.06.023
Синдром ектопічної АКТГ (огляд літератури та випадок із прак тики)
Guda, B. B., Tarashchenko, Y. М., Komisarenko, І. І., & Оstafiichuk, M. V. (2023) · Endokrynologia · doi:10.31793/1680-1466.2023.28-4.363
Geçgel, E., Alp, A., Kılıçarslan, E., Genek, D. G., & Huddam, B. (2023) · Ukrainian Journal of Nephrology and Dialysis · doi:10.31450/ukrjnd.1(81).2024.01
Saifi, S. A., Druce, I., Vickers, M. M., & Dennis, K. E. B. (2024) · Cureus · doi:10.7759/cureus.57852
AN ECTOPIC ACTH-SECRETING TUMOUR AFTER ADRENALECTOMY FOR PRIMARY ALDOSTERONISM
NELAJ, E., Kecaj, I., Feracaku, J., Asqeri, D., Gjata, A., Gradica, F., Ylli, A., & Tase, M. (2024) · Archives of the Balkan Medical Union · doi:10.31688/abmu.2024.59.1.15
A Cadaveric Case of Bilateral Adrenal Hyperplasia With Lung Cancer: A Paraneoplastic Syndrome?
Velayudham, G., Saqlain, M. S., Phillips, I., Saloway, J., & Katti, K. (2024) · Cureus · doi:10.7759/cureus.59443
Bel-Ange, A., & Grozinsky‐Glasberg, S. (2024) · Endocrinology · doi:10.1007/978-3-030-67823-4_10-1
COVID-19 ve Güncel Endokrinolojik Yaklaşımlar
Demirbaş, A., Aydemir, M., CANDAN, B. F., Ateş, C., Haytaoğlu, M. G., Demirtaş, L., Altuntaş, S. Ç., Genç, S., Tazegül, G., Kılıç, A. F., et al. (2022) · Akademisyen Kitabevi eBooks · doi:10.37609/akya.975
Fulminant hypercorticism due to ACTG producing pheochromocytoma
Useinova, Z. T., Pigarova, E. A., Beltsevich, D. G., Chevais, A., Dzeranova, L. K., Sitkin, I. I., Tarbaeva, N. V., Khairieva, А. V., Degtyarev, M. V., Platonova, N. M., et al. (2023) · Problems of Endocrinology · doi:10.14341/probl13374
Marsalisi, C., Zhang, Y., SOUSOU, J. M., Lam, L., Burstiner, L. S., Ferreira, J., & Najjar, N. (2024) · Cureus · doi:10.7759/cureus.69193
Ragnarsson, Ó., & Falhammar, H. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00114-x
Metadata
- Authors
- Young, J., Haissaguerre, M., Viera-Pinto, O., Chabre, O., Baudin, E., & Tabarin, A.
- Affiliations
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Cardiologique du Haut-Lévêque (FR)
- 1Department of Endocrinology, Paris-Sud University and Paris Saclay University, Assistance Publique Hôpitaux de Paris, Bicêtre Hospital, Le Kremlin-Bicêtre, France
- Université Joseph Fourier (FR)
- 4Endocrine Oncology and Nuclear Medicine Department, Gustave Roussy Cancer Institute, Paris-Sud University and Paris-Saclay University, Villejuif, France
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2020-04
- Volume
- 182
- Issue
- 4
- Pages
- R29-R58
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W3003251208
- Cited by
- 232
- References
- 189
- Citations by year
- 2026: 25 · 2025: 45 · 2024: 37 · 2023: 45 · 2022: 43 · 2021: 29 · 2020: 8
- FWCI
- 23.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Oncology › Neuroendocrine Tumor Research Advances
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- ectopic ACTH syndrome, Cushing's syndrome, hypercortisolism, neuroendocrine tumors, ACTH-secreting tumor, bilateral adrenalectomy, tumor resection, multidisciplinary management, endocrine emergencies
- MeSH terms
- ACTH Syndrome, Ectopic, Cushing Syndrome, Endocrinology, Humans, Treatment Outcome, Neuroendocrine Tumors
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