Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report
Abstract Background Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases. Case presentation We present here an 80-year-old man who had previously undergone s...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2022-07-01
|
| Series: | BMC Endocrine Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12902-022-01090-8 |
| _version_ | 1828329428214611968 |
|---|---|
| author | Fumi Saishouji Sarie Maeda Hideaki Hamada Noriko Kimura Ai Tamanoi Saiko Nishida Masaji Sakaguchi Motoyuki Igata Kiho Yokoo Fumi Kawakami Eiichi Araki Tatsuya Kondo |
| author_facet | Fumi Saishouji Sarie Maeda Hideaki Hamada Noriko Kimura Ai Tamanoi Saiko Nishida Masaji Sakaguchi Motoyuki Igata Kiho Yokoo Fumi Kawakami Eiichi Araki Tatsuya Kondo |
| author_sort | Fumi Saishouji |
| collection | DOAJ |
| description | Abstract Background Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases. Case presentation We present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient’s death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-β-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation. Conclusions We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis. |
| first_indexed | 2024-04-13T20:24:09Z |
| format | Article |
| id | doaj.art-c6ab455fae23415da45d8d1e2874545e |
| institution | Directory Open Access Journal |
| issn | 1472-6823 |
| language | English |
| last_indexed | 2024-04-13T20:24:09Z |
| publishDate | 2022-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Endocrine Disorders |
| spelling | doaj.art-c6ab455fae23415da45d8d1e2874545e2022-12-22T02:31:25ZengBMCBMC Endocrine Disorders1472-68232022-07-0122111210.1186/s12902-022-01090-8Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case reportFumi Saishouji0Sarie Maeda1Hideaki Hamada2Noriko Kimura3Ai Tamanoi4Saiko Nishida5Masaji Sakaguchi6Motoyuki Igata7Kiho Yokoo8Fumi Kawakami9Eiichi Araki10Tatsuya Kondo11Department of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Diagnostic Pathology, Department of Clinical Research, National Hospital Organization, Hakodate HospitalDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Metabolic Medicine, Faculty of Life Sciences, Kumamoto UniversityDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalDepartment of Diagnostic Pathology, Kumamoto University HospitalDepartment of Diagnostic Pathology, Kumamoto University HospitalDepartment of Metabolic Medicine, Faculty of Life Sciences, Kumamoto UniversityDepartment of Diabetes, Metabolism and Endocrinology, Kumamoto University HospitalAbstract Background Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases. Case presentation We present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient’s death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-β-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation. Conclusions We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.https://doi.org/10.1186/s12902-022-01090-8Ectopic ACTH-producing tumorRecurrent metastatic pheochromocytoma,CortisolCatecholamine,Positive feedback loop |
| spellingShingle | Fumi Saishouji Sarie Maeda Hideaki Hamada Noriko Kimura Ai Tamanoi Saiko Nishida Masaji Sakaguchi Motoyuki Igata Kiho Yokoo Fumi Kawakami Eiichi Araki Tatsuya Kondo Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report BMC Endocrine Disorders Ectopic ACTH-producing tumor Recurrent metastatic pheochromocytoma, Cortisol Catecholamine, Positive feedback loop |
| title | Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report |
| title_full | Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report |
| title_fullStr | Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report |
| title_full_unstemmed | Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report |
| title_short | Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report |
| title_sort | ectopic acth producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma a case report |
| topic | Ectopic ACTH-producing tumor Recurrent metastatic pheochromocytoma, Cortisol Catecholamine, Positive feedback loop |
| url | https://doi.org/10.1186/s12902-022-01090-8 |
| work_keys_str_mv | AT fumisaishouji ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT sariemaeda ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT hideakihamada ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT norikokimura ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT aitamanoi ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT saikonishida ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT masajisakaguchi ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT motoyukiigata ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT kihoyokoo ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT fumikawakami ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT eiichiaraki ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport AT tatsuyakondo ectopicacthproducingneuroendocrinetumoroccurringwithlargerecurrentmetastaticpheochromocytomaacasereport |