Cushing's syndrome caused by a neuroendocrine carcinoma of the ampulla of Vater with ectopic adrenocorticotropic hormone secretion

Robles Lázaro, Cristina; Herrero Ruiz, Ana; Sánchez Marcos, Ana Isabel

doi:10.1016/j.medcle.2018.02.008

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They represent 0.25–3% of all ampullary tumors<a class="elsevierStyleCrossRef" href="#bib0030">1</a> and only 0.05% of all types of neuroendocrine tumours.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> In the literature review carried out from 1900 to 2017 in Pubmed with the descriptors ampullary tumour, ectopic Cushing's syndrome, neuroendocrine carcinoma, neuroendocrine tumour, ACTH-secreting neuroendocrine carcinoma, somatostatin ampullary tumour, only one case of Cushing's syndrome caused by a neuroendocrine carcinoma of the ampulla of Vater with ACTH secretion has been published.<a class="elsevierStyleCrossRef" href="#bib0035">2</a>A 67-year-old man was admitted for recent-onset diabetes mellitus. His medical history included hypertension and dyslipidaemia. On examination, recent-onset oral candidiasis and bilateral oedema were observed.Admission lab results were: hypokalaemia (2mmol/l), impaired liver function tests: alanine aminotransferase 61U/l, gamma glutamyl transpeptidase 421U/l, lactic dehydrogenase 387U/l and hyperglycaemia of 475mg/dl. Arterial blood gases: metabolic alkalosis.Hormonal studies: increased plasma basal cortisol with a value of 216.4μg/dl (normal of 5–25) and plasma ACTH with a value of 285pg/ml (normal of 0–45).Given the laboratory anomalies, a thoracic-abdominal-pelvic CT was requested, showing liver metastasis and lymphadenopathies in the pancreatoduodenal space with thickening of the third portion of the duodenum. The enteroscopy detected an enlarged papilla with erythematous mucosa. An ampullary tumour was suspected, proceeding to its biopsy.The specimen's anatomopathological result confirmed the diagnosis of neuroendocrine carcinoma. The immunohistochemical study obtained the following results: chromogranin A+, synaptophysin±, mitotic index: 10/10 HPF, proliferative index (ki-67): approximately 80%.Biochemical markers of neuroendocrine tumour: elevation of chromogranin A 319ng/ml (normal of 0–100). Somatostatin, vasoactive intestinal peptide, gastrin and glucagon were normal.To complete the extension study and optimize the treatment, an octreotide scan was requested, which showed liver uptake. To control the symptoms of hypercortisolism, treatment with somatostatin analogues was initiated. No other drugs were associated due to their hepatotoxicity to the progressive deterioration of transaminases with respect to admission values. Chemotherapy treatment was initiated with cisplatin and etoposide. The patient developed a renal tubulopathy due to cisplatin and chemotherapy-induced bone marrow aplasia, worsening his baseline condition, causing his death three months after the initial diagnosis.Hormone hypersecretory neuroendocrine carcinomas originating in the duodenal vater ampulla are uncommon disorders and constitute an exceptional cause of Cushing's syndrome. This constitutes the second case published,<a class="elsevierStyleCrossRef" href="#bib0035">2</a> so it seems pertinent to communicate it in order to expand the limited information regarding its presentation, signs and therapeutic management.Poorly differentiated neuroendocrine carcinomas have a high degree of malignancy, are normally metastatic at diagnosis and according to the World Health Organization 2010 classification with a Ki 67 >20% and a mitotic index (10 HPF) >20.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>For the diagnosis of neuroendocrine carcinoma, it is necessary to evaluate its own markers, with chromogranin A and synaptophysin being the most specific.<a class="elsevierStyleCrossRef" href="#bib0030">1</a>The clinical presentation of ampullary tumours consists of jaundice as the most frequent symptom, abdominal pain, pancreatitis and weight loss. Less than 3% of patients develop a hormone hypersecretion syndrome.<a class="elsevierStyleCrossRef" href="#bib0035">2</a> The literature review has shown one case of gastrinoma and several somatostatinomas of the ampulla of Vater, but the ACTH-secreting neuroendocrine tumours is very rare.Somatostatin analogues are the first-line treatment to control symptoms in patients with functioning gastroenteropancreatic neuroendocrine tumours.<a class="elsevierStyleCrossRef" href="#bib0045">4</a> The octreotide scan allows us to assess which patients with unresectable or metastatic tumours are candidates to treatment with somatostatin analogues. Multiple studies have shown that 37–71% of gastroenteropancreatic neuroendocrine carcinomas show positivity for somatostatin receptors.<a class="elsevierStyleCrossRef" href="#bib0030">1</a> Neuroendocrine tumours that have Cushing's syndrome associated with ectopic ACTH secretion may experience relief of symptoms with somatostatin analogue therapy.<a class="elsevierStyleCrossRef" href="#bib0040">3</a>Surgery is the only treatment with the possibility of cure. Cisplatin/etoposide chemotherapy is recommended when there is liver metastasis in high-grade neuroendocrine carcinomas, regardless of the location of the primary tumour.<a class="elsevierStyleCrossRef" href="#bib0050">5</a>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Robles Lázaro C, Herrero Ruiz A, Sánchez Marcos AI. Síndrome de Cushing producido por un carcinoma neuroendocrino de la ampolla de Vater productor de hormona adrenocorticotropa ectópica. Med Clin (Barc). 2018;150:e21–e22." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0030" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuroendocrine carcinomas of the gastroenteropancreatic system: a comprehensive review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E.E. Ilett" 1 => "S.W. Langer" 2 => "I.H. Olsen" 3 => "B. Federspiel" 4 => "A. Kjær" 5 => "U. Knigge" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Diagnostics (Basel)" "fecha" => "2015" "volumen" => "5" "paginaInicial" => "119" "paginaFinal" => "176" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0035" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Kato" 1 => "K. Hayashi" 2 => "I. Naitoh" 3 => "K. Seno" 4 => "Y. Okada" 5 => "T. Ban" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3892/mco.2016.869" "Revista" => array:6 [ "tituloSerie" => "Mol Clin Oncol" "fecha" => "2016" "volumen" => "5" "paginaInicial" => "113" "paginaFinal" => "116" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27330779" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0040" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Klöppel" 1 => "A. Perren" 2 => "P.U. Heitz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann NY Acad Sci" "fecha" => "2004" "volumen" => "1014" "paginaInicial" => "13" "paginaFinal" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15153416" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0045" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Update on the role of somatostatin analogs for the treatment of patients with gastroenteropancreatic neuroendocrine tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C. Toumpanakis" 1 => "M.E. Caplin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.seminoncol.2012.11.006" "Revista" => array:6 [ "tituloSerie" => "Semin Oncol" "fecha" => "2013" "volumen" => "40" "paginaInicial" => "56" "paginaFinal" => "68" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23391113" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0050" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ENETS Consensus Guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Pavel" 1 => "E. Baudin" 2 => "A. Couvelard" 3 => "E. Krenning" 4 => "K. Öberg" 5 => "T. Steinmüller" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1159/000335597" "Revista" => array:7 [ "tituloSerie" => "Neuroendocrinology" "fecha" => "2012" "volumen" => "95" "paginaInicial" => "157" "paginaFinal" => "176" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22262022" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0022510X15004293" "estado" => "S300" "issn" => "0022510X" ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015000000008/v1_201805060427/S2387020618300809/v1_201805060427/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015000000008/v1_201805060427/S2387020618300809/v1_201805060427/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020618300809?idApp=UINPBA00004N"]

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Vol. 150. Issue 8.

Pages e21-e22 (April 2018)

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