Pancreatic Neuroendocrine Tumor with Ectopic Adrenocorticotropin Production upon Second Recurrence

Humboldt-Universität zu Berlin, Berlín, Berlin, Germany
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 09/2004; 89(8):3731-6. DOI: 10.1210/jc.2003-032164
Source: PubMed


We present a 54-yr-old woman with ectopic corticotropin syndrome caused by a neuroendocrine tumor of the pancreas. At initial presentation, the patient suffered from diarrhea, heartburn, and nonspecific abdominal pain. There was no evidence of Cushing's syndrome. A neuroendocrine tumor in the head of the pancreas with metastases into peripancreatic lymph nodes was diagnosed and completely resected. Fourteen months later, abdominal computed tomography and scintigraphy with (111)In-labeled octreotide suggested relapse of the tumor. The patient again had no evidence of Cushing's syndrome. A second in toto tumor resection was performed. Another 8 months later, the patient developed forgetfulness, depressive episodes, muscle weakness, new-onset hypertension, hypokalemia, plethora, diabetes mellitus, polyuria, and weight loss. Endocrine testing suggested a source of ectopic ACTH production. An octreotide scan showed an intense uptake ventromedial of the left kidney, an area that showed a mass lateral of the superior mesenteric artery on abdominal magnetic resonance imaging. A complete pancreatectomy with splenectomy and left-sided adrenalectomy were performed. At this second relapse, this neuroendocrine tumor clinically had changed its hormonal profile. Immunohistochemically, in contrast to primary tumor and first relapse, we found strong immunostaining for ACTH in tumor cells of the second relapse and a MIB-1 index greater than 20%. To our knowledge, this is the first report describing a pancreatic neuroendocrine tumor that started to secrete ACTH de novo at the time of the second relapse after two former complete tumor resections. This case underscores the pluripotency of neuroendocrine tumor cells and the importance of keeping in mind a possible shift in hormone production during tumor evolution and progression.

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Available from: Christian A Koch, Dec 22, 2014
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    • "In a series of 353 patients described by Wynick et al., 24 patients demonstrated de novo evidence of secretion of a second hormone during the course of the disease (median delay of 19 months and 92% reflecting liver metastases) [2]. Several reports have highlighted clinical cases of ectopic ACTH/Cushing’s syndrome, where secondary deposits stained strongly positive for ACTH despite a primary tumour being negative on ACTH staining [3]. In our case, ACTH staining was not deemed necessary with biochemical confirmation, considering the high cost involved and availability of ACTH staining in only a single United Kingdom centre. "
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    ABSTRACT: Background We report the case of a patient who had a non-functional metastatic pancreatic neuroendocrine tumour (pNET), which changed in functionality during the course of the disease. This case demonstrates the effectiveness of conventional cytotoxic chemotherapy in the management of select group of patients with this rare, challenging condition. Case presentation Our patient was a 34 year old man under oncology follow up, diagnosed with a non-functional metastatic pancreatic neuroendocrine tumour treated with a Whipple’s procedure two years ago. Despite treatment with somatostatin analogues and sunitinib, a tyrosine kinase inhibitor, he had demonstrated radiological progression of his metastatic disease. He now presented with a short history of Cushing’s syndrome. A presumptive diagnosis of a rapidly progressive, metastatic, functional pNET with ectopic ACTH production was made, confirmed biochemically and with liver biopsy. The proliferative index, Ki-67 of 20% of the liver biopsy prompted us to treat him with conventional cytotoxic chemotherapy using streptozocin, 5-fluorouracil and doxorubicin. Prior to its administration clinical and biochemical control of the hypercortisolemic state was achieved with metyrapone. However the clinical, biochemical and radiological response to chemotherapy was so dramatic obviating the need for metyrapone therapy. Conclusions Non-functional pNETs may evolve in their clinical and biologic behaviour producing functional hormonal syndromes. Chemotherapy may be an effective therapeutic modality in such circumstances.
    Full-text · Article · Aug 2014 · BMC Endocrine Disorders
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    • "The expressed hormones may or may not be secreted or biologically active, and the hormone expression profile of each tumor can change over time. It is common that an initially non-functioning PNET later triggers hormonal hypersecretion syndrome[38],[40],[48]. "
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    ABSTRACT: Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are understood to some degree while the molecular pathogenesis of PNETs is still unclear. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is not readily predictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally portend less favorable prognosis. Endocrine testing, imaging, and histological evidence are needed for accurate diagnosis of PNETs. An "aggressive" treatment approach with 4 components: surgery, locoregional therapy, systemic therapy, and complication control, has becomes a trend in academic centers throughout the world. The optimal use of the multiple modalities of systemic therapy is still being developed; efficacy, safety, availability, and cost should be considered when treating a specific patient. Clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including a novel Mahvash disease, are summarized.
    Full-text · Article · Dec 2012 · Chinese journal of cancer
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    • "Among ectopic ACTH-producing lesions, approximately 50% originate from intrathoracic tumors, usually small cell carcinomas [2-6]. Other well-described tumors of ectopic ACTH-production include medullary thyroid carcinoma, pheochromocytoma, as well as carcinomas of the thymus and pancreas [2,7-11]. Except for the pancreas, other organs and locations for ACTH-producing tumors in the abdomen, i.e. appendix, duodenum, ileum, colon, anal canal, uterine cervix, and ovary are uncommon [12-20]. "
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    ABSTRACT: ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled (111)In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from explorative radioguided surgery using (111)In-pentetreotide and a gamma probe.
    Preview · Article · Feb 2006 · BMC Cancer
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