The Ectopic Adrenocorticotropin Syndrome: Clinical Features, Diagnosis, Management, and Long-Term Follow-Up

Isidori, Andrea M.; Kaltsas, Gregory; Pozza, Carlotta; Frajese, Vanni; Newell‐Price, John; Reznek, Rodney H.; Jenkins, Paul J.; Monson, John P.; Grossman, Ashley; Besser, G. M.

doi:10.1210/jc.2005-1542

Cited by 451 publications

(509 citation statements)

References 36 publications

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“…We decided not to follow this approach, because we believe that 100% specificity is difficult to obtain with the CRH test. It has been well documented that a small number of patients with ECS show a clear cortisol and ACTH response to CRH, especially patients with carcinoids (13,14,15,16,17,18,19). Presetting specificity to 100% will always lead to a pronounced reduction in sensitivity.…”

Section: Discussionmentioning

confidence: 99%

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

Ritzel

Beuschlein

Berr

et al. 2015

European Journal of Endocrinology

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Objective: The aim of the present study was to validate criteria of corticotropin-releasing hormone (CRH) stimulation and 8 mg dexamethasone suppression (high-dose dexamethasone suppression, HDDS) to distinguish the etiology of ACTH-dependent Cushing's syndrome. Subjects and methods: We retrospectively analyzed cortisol and ACTH after the injection of 100 mg human CRH in confirmed Cushing's disease (CD, nZ78) and confirmed ectopic Cushing's syndrome (ECS, nZ18). Cortisol and ACTH increase (in percentage above basal (% B )) at each time point, maximal increase (Dmax % B ), and area under the curve (AUC % B ) were analyzed using receiver operator characteristics (ROC) curve analyses. Cortisol suppression (% B ) after 8 mg of dexamethasone was evaluated as a supplementary criterion. Results: An increase in ACTH of R43% B at 15 min after CRH was the strongest predictor of CD, with a positive likelihood ratio of 14.0, a sensitivity of 83%, a specificity of 94%, a positive predictive value of 98% and a negative predictive value of 58%. All of the other criteria of stimulated ACTH and cortisol levels were not superior in predicting CD in response to CRH injection. The addition of cortisol suppression by dexamethasone did not increase the discriminatory power. However, the combination of a positive ACTH response at 15 min and a positive HDDS test excluded ECS in all cases. Conclusion: The present findings support the use of plasma ACTH levels 15 min after the injection of human CRH as a response criterion for distinguishing between CD and ECS. The addition of the HDDS test is helpful for excluding ECS when both tests are positive.

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Section: Discussionmentioning

confidence: 99%

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

Ritzel

Beuschlein

Berr

et al. 2015

European Journal of Endocrinology

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“…in metastatic disease or in the case of occult tumors). Tumor-directed therapy involves an individualized approach, and can include somatostatin analogues, systemic chemotherapy, interferon-α, chemoembolization, radiofrequency ablation, and radiation therapy (21)(22)(23)(24). In the present case, surgery for tumor resection was attempted three times, but the tumor was locally invasive since diagnosis.…”

Section: Treatment and Managementmentioning

confidence: 86%

A rare case of Cushing syndrome by cyclic ectopic-ACTH

Farage

Costa²,

Godoy-Matos

2012

Arq Bras Endocrinol Metab

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SUMMARYACTH-dependent Cushing syndrome (CS) due to ectopic ACTH production is most times difficult to manage. The identification of the source of ACTH may take many years. Surgery or chemotherapy for the primary tumor is not always possible. Control of Cushing symptoms is many times achieved using medication, or bilateral adrenalectomy in refractory cases. This case presents a Brazilian male who showed severe hypertension, mood changes, muscle weakness, darkening of skin, and increased abdominal fat. An investigation for Cushing syndrome was carried out and, after a four-year follow-up, a carotid glomus tumor (chemodectoma) was confirmed, a rare ectopic ACTH-producing tumor. Besides, the patient presented cyclic Cushing syndrome that was exacerbated by diverticulitis episodes. This case presents interesting pitfalls on diagnosis and management of ACTH-dependent CS. This is the only report of a chemodectoma that produced ACTH in the literature. Arq Bras Endocrinol Metab. 2012;56(5):324-30 SUMÁRIO A síndrome de Cushing ACTH-dependente causada por produção ectópica de ACTH é, muitas vezes, difícil de diagnosticar e conduzir. A identificação da fonte produtora de ACTH pode demorar muitos anos. A cirurgia ou quimioterapia para o tumor primário nem sempre é possível, sendo o controle do hipercortisolismo alcançado com uso de fármacos ou adrenalectomia bilateral, nos casos refratários. Este caso apresenta um homem com hipertensão grave, mudança de humor, fraqueza proximal, escurecimento da pele e aumento de gordura abdominal. A investigação para síndrome de Cushing foi feita e, após quatro anos de acompanhamento, confirmou--se um tumor de glomus carotídeo (quemodectoma), causa rara de tumor secretor de ACTH. Nesse período, o paciente apresentou síndrome de Cushing cíclica, exacerbada por crises de diverticulite. O caso ilustra pontos importantes no diagnóstico, no acompanhamento e na condução da síndrome de Cushing ACTH-dependente, sendo este o único caso de tumor de glomus de carótida produzindo ACTH descrito na literatura médica. Arq Bras Endocrinol Metab. 2012;56(5):324-30

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“…Less commonly, paraneoplastic CS (PN-CS) may develop from neuroendocrine cells of the thymus, MTC, pancreas or chromaffin cell tumours (phaeochromocytomas, paragangliomas and neuroblastomas) (Ilias et al 2005, Isidori et al 2006. In a recent study performed by Kamp and coworkers looking at a large cohort of patients with thoracic and GEP-NETs, the reported prevalence of PN-CS was 3.2% (Kamp et al 2016).…”

Section: Cushing's Syndrome (Cs)mentioning

confidence: 99%

“…Endocrine and neuroendocrine tumours producing PN-CS are in the majority of low malignant potential although this may change during the course of the disease (Ilias et al 2005, Isidori et al 2006, Li et al 2016. Well differential lung NETs (typical and atypical carcinoids) account for the majority of PN-CS, approximately 36-46%, producing a clinical and biochemical syndrome resembling pituitary dependent CS (Li et al 2016, Zhang & Zhao 2016.…”

Section: Cushing's Syndrome (Cs)mentioning

confidence: 99%

Paraneoplastic endocrine syndromes

Dimitriadis

Angelousi

Weickert

et al. 2017

Endocrine-Related Cancer

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The majority of neoplasms are responsible for symptoms caused by mass effects to surrounding tissues and/or through the development of metastases. However, occasionally neoplasms, with or without endocrine differentiation, acquire the ability to secrete a variety of bioactive substances or induce immune cross-reactivity with the normal tissues that can lead to the development of characteristic clinical syndromes. These syndromes are named endocrine paraneoplastic syndromes when the specific secretory components (hormones, peptides or cytokines) are unrelated to the anticipated tissue or organ of origin. Endocrine paraneoplastic syndromes can complicate the patient's clinical course, response to treatment, impact prognosis and even be confused as metastatic spread. These syndromes can precede, occur concomitantly or present at a later stage of tumour development, and along with the secreted substances constitute the biological 'fingerprint' of the tumour. Their detection can facilitate early diagnosis of the underlying neoplasia, monitor response to treatment and/or detect early recurrences following successful initial management. Although when associated with tumours of low malignant potential they usually do not affect long-term outcome, in cases of highly malignant tumours, endocrine paraneoplastic syndromes are usually associated with poorer survival outcomes. Recent medical advances have not only improved our understanding of paraneoplastic syndrome pathogenesis in general but also enhanced their diagnosis and treatment. Yet, given the rarity of endocrine paraneoplastic syndromes, there is a paucity of prospective clinical trials to guide management. The development of well-designed prospective multicentre trials remains a priority in the field in order to fully characterise these syndromes and provide evidence-based diagnostic and therapeutic protocols.

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The Ectopic Adrenocorticotropin Syndrome: Clinical Features, Diagnosis, Management, and Long-Term Follow-Up

Abstract: A variety of tests and imaging studies are necessary for the correct diagnosis of the EAS, but even then, up to 20% of cases present a covert or occult EAS syndrome. These cases require a prolonged follow-up, review, and repetition of diagnostic tests and scans.

Cited by 451 publications

References 36 publications

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

ACTH after 15 min distinguishes between Cushing's disease and ectopic Cushing's syndrome: a proposal for a short and simple CRH test

A rare case of Cushing syndrome by cyclic ectopic-ACTH

Paraneoplastic endocrine syndromes

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