Distinct clinical course of neuroendocrine tumors presenting ectopic ACTH tissue expression and secretion

2020 ◽  
Author(s):  
Michalina Oszywa ◽  
Martyna Borowczyk ◽  
Ewelina Szczepanek-Parulska ◽  
Paweł Gut ◽  
Marek Ruchała
Keyword(s):  
Neuroendocrine Tumors ◽  
Clinical Course ◽  
Tissue Expression ◽  
Ectopic Acth

scholarly journals Ectopic ACTH syndrome of different origin—Diagnostic approach and clinical outcome. Experience of one Clinical Centre

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242679
Author(s):  
Joanna Ewelina Paleń-Tytko ◽  
Elwira Maria Przybylik-Mazurek ◽  
Ewelina Joanna Rzepka ◽  
Dorota Magdalena Pach ◽  
Anna Stanisława Sowa-Staszczak ◽  
...  
Keyword(s):  
Weight Loss ◽  
Neuroendocrine Tumors ◽  
Muscle Weakness ◽  
Clinical Course ◽  
Cushing Syndrome ◽  
Ectopic Acth Syndrome ◽  
High Dose ◽  
Ectopic Acth ◽  
Clinical Centre ◽  
Cortisol Levels

Purpose Ectopic Cushing Syndrome (EAS) is a rare condition responsible for about 5–20% of all Cushing syndrome cases. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The aim of this study is to present a 20-year experience in the diagnosis and clinical course of patients with EAS in a single Clinical Centre in Southern Poland as well as a comparison of clinical course and outcomes depending on the source of ectopic ACTH production–especially neuroendocrine tumors with other neoplasms. Methods Twenty-four patients were involved in the clinical study with EAS diagnosed at the Department of Endocrinology between years 2000 and 2018. The diagnosis of EAS was based on the clinical presentation, hypercortisolemia with high ACTH levels, high dose dexamethasone suppression test and/or corticotropin-releasing hormone tests. To find the source of ACTH various imaging studies were performed. Results Half of the patients were diagnosed with neuroendocrine tumors, whereby muscle weakness was the leading symptom. Typical cushingoid appearance was seen in merely a few patients, and weight loss was more common than weight gain. Patients with neuroendocrine tumors had significantly higher midnight cortisol levels than the rest of the group. Among patients with infections, we observed a significantly higher concentrations of cortisol 2400 levels in gastroenteropancreatic neuroendocrine tumors. Chromogranin A correlated significantly with potassium in patients with neuroendocrine tumors and there was a significant correlation between ACTH level and severity of hypokalemia. Conclusion EAS is not common, but if it occurs it increases the mortality of patients; therefore, it should be taken into consideration in the case of coexistence of severe hypokalemia with hypertension and muscle weakness, especially when weight loss occurs. Because the diagnosis of gastroenteropancreatic neuroendocrine tumor worsens the prognosis-special attention should be paid to these patients.

Peritoneal carcinomatosis from small intestinal neuroendocrine tumors: Clinical course and genetic profiling

Surgery ◽  
2014 ◽  
Vol 156 (6) ◽  
pp. 1512-1522 ◽  
Author(s):  
Olov Norlén ◽  
Katarina Edfeldt ◽  
Goran Akerstrom ◽  
Gunnar Westin ◽  
Per Hellman ◽  
...  
Keyword(s):  
Peritoneal Carcinomatosis ◽  
Neuroendocrine Tumors ◽  
Clinical Course ◽  
Genetic Profiling ◽  
Small Intestinal

Clinical Course of Neuroendocrine Tumors With Different Origins (the Pancreas, Gastrointestinal Tract, and Lung)

2012 ◽  
Vol 35 (6) ◽  
pp. 549-556 ◽  
Author(s):  
Su-Jung Kim ◽  
Jin Won Kim ◽  
Do-Youn Oh ◽  
Sae-Won Han ◽  
Se-Hoon Lee ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Neuroendocrine Tumors ◽  
Clinical Course ◽  
Different Origins

scholarly journals A rare case of duodenal carcinoid presenting as ectopic Cushing’s syndrome

2019 ◽  
Vol 6 (3) ◽  
pp. 959
Author(s):  
Siddharth Pugalendhi ◽  
Tarun Kumar Dutta ◽  
Dhivya . ◽  
Kiran Yadav
Keyword(s):  
Neuroendocrine Tumors ◽  
Cushing’S Syndrome ◽  
Cushing Syndrome ◽  
Somatostatin Analogues ◽  
Cushing's Syndrome ◽  
High Dose ◽  
Ectopic Acth ◽  
High Dose Dexamethasone ◽  
Ectopic Acth Production ◽  
Duodenal Carcinoid

ACTH-dependent Cushing syndrome (CS) due to an ectopic source is responsible for approximately 10-15% cases of Cushing’s syndrome. It is associated with various tumors such as small cell lung cancer and well-differentiated bronchial or gastrointestinal neuroendocrine tumors. Many a times ectopic ACTH production is difficult to manage, and identification of the source may take many years.  Hormonal diagnostics include assessments in basic conditions as well as dynamic tests, such as the high-dose dexamethasone suppression test and corticotrophin releasing hormone (CRH) stimulation test. Treatment selection depends on the type of tumor and its extent. In the case of neuroendocrine tumors, the main treatments are surgery and administration of somatostatin analogues or bilateral adrenalectomy in refractory cases and if the source remains unidentified. Here, we report a case who presented with features of Cushing’s syndrome which eventually through workup led us to a diagnosis of duodenal carcinoid producing ectopic ACTH which is extremely rare and was successfully treated.

The Clinical Features and Molecular Mechanisms of ACTH-secreting Pancreatic Neuroendocrine Tumors

2020 ◽  
Vol 105 (11) ◽  
Author(s):  
Cui Zhang ◽  
Jiabin Jin ◽  
Jing Xie ◽  
Lei Ye ◽  
Tingwei Su ◽  
...  
Keyword(s):  
Clinical Features ◽  
Neuroendocrine Tumors ◽  
Molecular Mechanisms ◽  
Transarterial Embolization ◽  
Cpg Methylation ◽  
Pancreatic Neuroendocrine Tumors ◽  
Ectopic Acth ◽  
Primary Tumors ◽  
Free Cortisol ◽  
Acth Secreting

Abstract Objective Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis. Methods Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation. Results All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas. Conclusions ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs.

scholarly journals Ectopic adrenocorticotropic hormone syndrome associated with olfactory neuroblastoma: acquirement of adrenocorticotropic hormone expression during disease course as shown by serial immunohistochemistry examinations

2018 ◽  
Vol 46 (11) ◽  
pp. 4760-4768 ◽  
Author(s):  
Manabu Kadoya ◽  
Masafumi Kurajoh ◽  
Akio Miyoshi ◽  
Takuhito Shoji ◽  
Tomonori Terada ◽  
...  
Keyword(s):  
Adrenocorticotropic Hormone ◽  
Clinical Course ◽  
Elevated Serum ◽  
Malignant Neoplasm ◽  
Olfactory Neuroblastoma ◽  
Serum Levels ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
First Case ◽  
Ectopic Adrenocorticotropic Hormone

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a condition of endogenous hypercortisolism sustained by an extrapituitary ACTH-secreting tumor. Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the sinonasal tract and is derived from the olfactory epithelium. Because the paranasal sinus is not a common site of EAS, the development of ONB in patients with EAS is rare. We herein report the first known case of ONB with acquirement of ACTH production during the clinical course as proven by immunohistochemistry. A 50-year-old man diagnosed with ONB was referred to our department in July 2015 because of hypokalemia, hyperglycemia, decreased eosinophil and granulocyte counts, and elevated serum levels of ACTH and cortisol. Although two previous ONB biopsy specimens (2011 and 2014) showed no ACTH immunoreactivity, a newly obtained specimen in August 2015 clearly showed ACTH immunoreactivity. This is the first case of ectopic ACTH syndrome associated with an ONB that acquired the ability to express ACTH during its clinical course as shown by serial immunohistochemical examinations.

scholarly journals Prognostic factors in ectopic Cushing’s syndrome due to neuroendocrine tumors: a multicenter study

2017 ◽  
Vol 176 (4) ◽  
pp. 453-461 ◽  
Author(s):  
Maria Vittoria Davi’ ◽  
Elisa Cosaro ◽  
Serena Piacentini ◽  
Giuseppe Reimondo ◽  
Nora Albiger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Prognostic Factors ◽  
Neuroendocrine Tumors ◽  
Cushing’S Syndrome ◽  
Distant Metastases ◽  
Cushing's Syndrome ◽  
Primary Role ◽  
Ectopic Acth ◽  
Term Survival ◽  
Ectopic Cushing’S Syndrome

Objective Evidence is limited regarding outcome of patients with ectopic Cushing’s syndrome (ECS) due to neuroendocrine tumors (NETs). Design We assessed the prognostic factors affecting the survival of patients with NETs and ECS. Methods Retrospective analysis of clinicopathological features, severity of hormonal syndrome, treatments from a large cohort of patients with NETs and ECS collected from 17 Italian centers. Results Our series included 110 patients, 58.2% female, with mean (±s.d.) age at diagnosis of 49.5 ± 15.9 years. The main sources of ectopic ACTH were bronchial carcinoids (BC) (40.9%), occult tumors (22.7%) and pancreatic (p)NETs (15.5%). Curative surgery was performed in 56.7% (70.2% of BC, 11% of pNETs). Overall survival was significantly higher in BC compared with pNETs and occult tumors (P = 0.033) and in G1-NETs compared with G2 and G3 (P = 0.007). Negative predictive factors for survival were severity of hypercortisolism (P < 0.02), hypokalemia (P = 0.001), diabetes mellitus (P = 0.0146) and distant metastases (P < 0.001). Improved survival was observed in patients who underwent NET removal (P < 0.001). Adrenalectomy improved short-term survival. Conclusions Multiple factors affect prognosis of ECS patients: type of NET, grading, distant metastases, severity of hypercortisolism, hypokalemia and diabetes mellitus. BCs have the highest curative surgical rate and better survival compared with occult tumors and pNETs. Hypercortisolism plays a primary role in affecting outcome and quality of life; therefore, prompt and vigorous treatment of hormonal excess by NET surgery and medical therapy should be a key therapeutic goal. In refractory cases, adrenalectomy should be considered as it affects outcome positively at least in the first 2 years.

scholarly journals Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors

2016 ◽  
Vol 174 (3) ◽  
pp. 271-280 ◽  
Author(s):  
K Kamp ◽  
R A Alwani ◽  
E Korpershoek ◽  
G J H Franssen ◽  
W W de Herder ◽  
...  
Keyword(s):  
Neuroendocrine Tumors ◽  
Small Cell Lung Carcinoma ◽  
Large Cohort ◽  
Ectopic Acth Syndrome ◽  
Gastroenteropancreatic Neuroendocrine Tumors ◽  
Ectopic Acth ◽  
Cell Lung Carcinoma ◽  
Tertiary Referral Center ◽  
Relative Contribution

ObjectiveSeveral series report on the relative contribution of ectopic ACTH syndrome (EAS) in the spectrum of Cushing's syndrome. However, prevalence of EAS in patients with thoracic or gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is currently unknown.Design We assessed, in a tertiary referral center, the prevalence of EAS in a large cohort of thoracic and GEP-NET patients including clinical, biochemical, and radiological features; management; and treatment outcome.Methods In total, 918 patients with thoracic or GEP-NETs were studied (1993–2012). Multiple endocrine neoplasia type 1 and small cell lung carcinoma patients were excluded. Differentiation between synchronous, metachronous, and cyclic occurrence of EAS was made.Results Out of the 918 patients with thoracic and GEP-NETs (469 males and 449 females; median age 58.7 years (range: 17.3–87.3)), 29 patients (3.2%) had EAS (ten males and 19 females; median age 48.1 years (range: 24.7–77.9)). EAS occurred synchronously in 23 patients (79%), metachronously in four patients (14%), and cyclical in two patients (7%) respectively. NETs causing EAS included lung/bronchus (n=9), pancreatic (n=9), and thymic (n=4). In four patients, the cause of EAS was unknown (n=4). Median overall survival (OS) of non-EAS thoracic and GEP-NET patients was 61.2 months (range: 0.6–249.4). Median OS of EAS patients was 41.4 months (range: 2.2–250.9). After comparison, only the first 5-year survival was significantly shorter (P=0.013) in EAS patients.Conclusion Prevalence of EAS in this large cohort of patients with thoracic and GEP-NETs was 3.2%. EAS was mostly caused by thoracic and pancreatic NETs. First 5-year survival of EAS patients was shorter compared with non-EAS patients.

scholarly journals Occult Carcinoid Causes Cushing’s Syndrome

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A594-A595
Author(s):  
Sabrina Meftali ◽  
Rebecca Unterborn ◽  
Amanda Gifford ◽  
Bankim Bhatt
Keyword(s):  
Weight Gain ◽  
Carcinoid Tumor ◽  
Neuroendocrine Tumors ◽  
Cushing’S Syndrome ◽  
Pulmonary Nodule ◽  
Cushing's Syndrome ◽  
Ectopic Acth Syndrome ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Ectopic Cushing’S Syndrome

Abstract Introduction: Lung neuroendocrine tumors (NETs) are a common cause of ectopic ACTH-secretion. Only 3% of NETs cause Cushing’s syndrome1; the majority are small and may be radiographically occult. Additionally, the responses to dexamethasone, metyrapone, and oCRF can be indistinguishable from that observed in pituitary Cushing’s disease2. These challenges lead to misdiagnosis and unnecessary procedures. Case Description: 45-year-old male presented for resection of right-sided pulmonary carcinoid tumor. He was diagnosed with Cushing’s syndrome in 2011 when he experienced uncontrolled hypertension and excessive weight gain with elevations in cortisol and ACTH levels. He underwent transsphenoidal pituitary resection in May 2011 for a possible pituitary microadenoma. Post-operative worsening hypertension, weight gain, and striae led to bilateral adrenalectomy in November 2011, complicated by retroperitoneal hemorrhage and resuscitation-induced pulmonary edema. On chest CT in early 2012, an 8 mm incidental right pulmonary nodule was documented. 8 years later, chest imaging for mild COVID-19 infection again revealed a right-sided pulmonary nodule. He underwent CT-guided biopsy of the nodule in July 2020 with pathology demonstrating carcinoid histology. Right lower lobectomy was performed. Pre-operative ACTH was 1673 pg/mL (normal: 10-60 pg/mL) and post-operative ACTH was 16 pg/mL. The resected tumor stained positive for ACTH, confirming that carcinoid tumor was the source of Cushing’s for the past decade. Conclusion: The diagnosis of ectopic Cushing’s syndrome can be elusive, leading to surgeries with significant morbidity, as seen in our patient. In one retrospective review, 14% of patients with Cushing’s had transsphenoidal resection before they were diagnosed with an ectopic source3. Ectopic Cushing’s syndrome can be a challenging diagnosis to make and a multidisciplinary approach with close collaboration between endocrinologist, radiologist, surgeon and pathologist may increase the diagnosis accuracy. Citations: 1Kamp, K, Alwani, R A, Korpershoek, E, Franssen, G., de Herder, W W, & Feelders, R A. (2016). Prevalence and clinical features of the ectopic ACTH syndrome in patients with gastroenteropancreatic and thoracic neuroendocrine tumors, European Journal of Endocrinology, 174(3), 271-280. Retrieved Jan 15, 2021, from https://eje.bioscientifica.com/view/journals/eje/174/3/271.xml 2Malchoff CD, Orth DN, Abboud C, Carney JA, Pairolero PC, Carey RM. Ectopic ACTH syndrome caused by a bronchial carcinoid tumor responsive to dexamethasone, metyrapone, and corticotropin-releasing factor. The American Journal of Medicine. 1988;84(4):760-764. doi:10.1016/0002-9343(88)90116-7 3Ioannis Ilias, David J. Torpy, Karel Pacak, Nancy Mullen, Robert A. Wesley, Lynnette K. Nieman,Cushing’s Syndrome Due to Ectopic Corticotropin Secretion: Twenty Years’ Experience at theNational Institutes of Health, The Journal of Clinical Endocrinology & Metabolism, Volume 90, Issue8, 1 August 2005, Pages 4955–4962, https://doi.org/10.1210/jc.2004-2527

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