Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report

Introduction: Neuroendocrine neoplasms encompass well-differentiated tumors (NETs) and poorly differentiated carcinomas (neuroendocrine carcinomas [NECs]), which are distinguished by their clinical behavior and molecular characteristics. They can cause paraneoplastic syndromes, such as ectopic adren...

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Main Authors: Michel Meyers, Ahmad Awada, Ioannis Karfis, Daphné t'Kint de Roodenbeke, Hugo Couvert, Charlotte Hanssens, Alain Hendlisz, Natacha Driessens
Format: Article
Language:English
Published: Karger Publishers 2024-10-01
Series:Case Reports in Oncology
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Online Access:https://beta.karger.com/Article/FullText/540707
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author Michel Meyers
Ahmad Awada
Ioannis Karfis
Daphné t'Kint de Roodenbeke
Hugo Couvert
Charlotte Hanssens
Alain Hendlisz
Natacha Driessens
author_facet Michel Meyers
Ahmad Awada
Ioannis Karfis
Daphné t'Kint de Roodenbeke
Hugo Couvert
Charlotte Hanssens
Alain Hendlisz
Natacha Driessens
author_sort Michel Meyers
collection DOAJ
description Introduction: Neuroendocrine neoplasms encompass well-differentiated tumors (NETs) and poorly differentiated carcinomas (neuroendocrine carcinomas [NECs]), which are distinguished by their clinical behavior and molecular characteristics. They can cause paraneoplastic syndromes, such as ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (CS), necessitating prompt recognition and management due to severe hypercortisolism. Case Presentation: A 66-year-old patient with a 3-year history of metastatic mixed neuroendocrine-non-neuroendocrine neoplasm with a NEC and adenocarcinoma component originating from the vulva presented to the emergency department with dyspnea and fatigue. Upon clinical examination, we found widespread hyperpigmentation, a moon-face appearance, hirsutism, buffalo hump, and muscle atrophy. Laboratory investigations revealed severe hypokalemia (2.3 mmol/L), elevated serum cortisol (1,726 nmol/L) and ACTH (194 ng/L) levels. Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS. Thoracoabdominal computed tomography (CT) scan demonstrated progressive neoplastic disease in the liver, kidney, lymph nodes, peritoneum, and lungs. Brain magnetic resonance imaging indicated multifocal metastatic infiltration but no evidence of pituitary adenoma. Interestingly, despite a previously negative 68Ga-DOTATATE positron emission tomography (PET)/CT performed 1 year prior, there was moderate somatostatin receptor (SSTR) expression in lymphatic, pulmonary, peritoneal, and bone tissues, suggesting the presence of a component with redifferentiation and re-expression of the SSTR. After the workup, the patient was admitted to a supportive care facility. Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs. Unfortunately, the patient was too frail to benefit from peptide receptor radionuclide therapy (PRRT). Conclusion: This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68Ga-DOTATATE PET/CT.
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spelling doaj-art-7ca2e3a8e2aa43fd869c0963c90f4ea62025-08-20T02:12:47ZengKarger PublishersCase Reports in Oncology1662-65752024-10-011711146115610.1159/000540707540707Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case ReportMichel Meyers0Ahmad Awada1Ioannis Karfis2Daphné t'Kint de Roodenbeke3Hugo Couvert4Charlotte Hanssens5Alain Hendlisz6Natacha Driessens7Department of Medical Oncology, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Medical Oncology, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Nuclear Medicine, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Oncogenetic, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Internal Medicine, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Medical Oncology, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Digestive Oncology, ENETS Center of Excellence, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Université Libre de Bruxelles, Brussels, BelgiumDepartment of Endocrinology, ENETS Center of Excellence, Hôpital Universitaire de Bruxelles, Hôpital Erasme, Université Libre de Bruxelles, Brussels, BelgiumIntroduction: Neuroendocrine neoplasms encompass well-differentiated tumors (NETs) and poorly differentiated carcinomas (neuroendocrine carcinomas [NECs]), which are distinguished by their clinical behavior and molecular characteristics. They can cause paraneoplastic syndromes, such as ectopic adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (CS), necessitating prompt recognition and management due to severe hypercortisolism. Case Presentation: A 66-year-old patient with a 3-year history of metastatic mixed neuroendocrine-non-neuroendocrine neoplasm with a NEC and adenocarcinoma component originating from the vulva presented to the emergency department with dyspnea and fatigue. Upon clinical examination, we found widespread hyperpigmentation, a moon-face appearance, hirsutism, buffalo hump, and muscle atrophy. Laboratory investigations revealed severe hypokalemia (2.3 mmol/L), elevated serum cortisol (1,726 nmol/L) and ACTH (194 ng/L) levels. Urinary free cortisol measurement was 21-fold the upper limit of the reference range (3,614.0 nmol/24 h), and cortisol concentration did not decrease after 1mg-dexamethasone suppression test (1,812 nmol/L for an expected value <50 nmol/L), confirming the ACTH-dependent CS. Thoracoabdominal computed tomography (CT) scan demonstrated progressive neoplastic disease in the liver, kidney, lymph nodes, peritoneum, and lungs. Brain magnetic resonance imaging indicated multifocal metastatic infiltration but no evidence of pituitary adenoma. Interestingly, despite a previously negative 68Ga-DOTATATE positron emission tomography (PET)/CT performed 1 year prior, there was moderate somatostatin receptor (SSTR) expression in lymphatic, pulmonary, peritoneal, and bone tissues, suggesting the presence of a component with redifferentiation and re-expression of the SSTR. After the workup, the patient was admitted to a supportive care facility. Hypercortisolism symptoms were effectively managed with an adrenal enzyme inhibitor (ketoconazole) in combination with somatostatin analogs. Unfortunately, the patient was too frail to benefit from peptide receptor radionuclide therapy (PRRT). Conclusion: This redifferentiation phenomenon in neuroendocrine tumors should be further investigated as patients might be, under certain conditions, eligible for PRRT. Therefore, we suggest that newly occurring paraneoplastic syndromes in patients with NEC should always be evaluated using 68Ga-DOTATATE PET/CT.https://beta.karger.com/Article/FullText/54070768ga-dotatate positron emission tomography/computed tomographymixed neuroendocrine non-neuroendocrine neoplasmpeptide receptor radionuclide therapysomatostatin receptorectopic adrenocorticotropic hormone secretionneuroendocrine neoplasm
spellingShingle Michel Meyers
Ahmad Awada
Ioannis Karfis
Daphné t'Kint de Roodenbeke
Hugo Couvert
Charlotte Hanssens
Alain Hendlisz
Natacha Driessens
Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
Case Reports in Oncology
68ga-dotatate positron emission tomography/computed tomography
mixed neuroendocrine non-neuroendocrine neoplasm
peptide receptor radionuclide therapy
somatostatin receptor
ectopic adrenocorticotropic hormone secretion
neuroendocrine neoplasm
title Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
title_full Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
title_fullStr Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
title_full_unstemmed Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
title_short Ectopic ACTH-Dependent Cushing’s Syndrome Emerging at a Late Stage of a Mixed Histology Neuroendocrine Neoplasm: A Case Report
title_sort ectopic acth dependent cushing s syndrome emerging at a late stage of a mixed histology neuroendocrine neoplasm a case report
topic 68ga-dotatate positron emission tomography/computed tomography
mixed neuroendocrine non-neuroendocrine neoplasm
peptide receptor radionuclide therapy
somatostatin receptor
ectopic adrenocorticotropic hormone secretion
neuroendocrine neoplasm
url https://beta.karger.com/Article/FullText/540707
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