Letter to the Editor
Cushing's syndrome caused by a neuroendocrine carcinoma of the ampulla of Vater with ectopic adrenocorticotropic hormone secretion
Síndrome de Cushing producido por un carcinoma neuroendocrino de la ampolla de Vater productor de hormona adrenocorticotropa ectópica
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They represent 0.25–3% of all ampullary tumors<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">1</span></a> and only 0.05% of all types of neuroendocrine tumours.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">2</span></a> In the literature review carried out from 1900 to 2017 in Pubmed with the descriptors <span class="elsevierStyleItalic">ampullary tumour</span>, <span class="elsevierStyleItalic">ectopic Cushing's syndrome</span>, <span class="elsevierStyleItalic">neuroendocrine carcinoma</span>, <span class="elsevierStyleItalic">neuroendocrine tumour</span>, ACTH-<span class="elsevierStyleItalic">secreting neuroendocrine carcinoma</span>, <span class="elsevierStyleItalic">somatostatin ampullary tumour</span>, 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"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">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.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Admission lab results were: hypokalaemia (2<span class="elsevierStyleHsp" style=""></span>mmol/l), impaired liver function tests: alanine aminotransferase 61<span class="elsevierStyleHsp" style=""></span>U/l, gamma glutamyl transpeptidase 421<span class="elsevierStyleHsp" style=""></span>U/l, lactic dehydrogenase 387<span class="elsevierStyleHsp" style=""></span>U/l and hyperglycaemia of 475<span class="elsevierStyleHsp" style=""></span>mg/dl. Arterial blood gases: metabolic alkalosis.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Hormonal studies: increased plasma basal cortisol with a value of 216.4<span class="elsevierStyleHsp" style=""></span>μg/dl (normal of 5–25) and plasma ACTH with a value of 285<span class="elsevierStyleHsp" style=""></span>pg/ml (normal of 0–45).</p><p id="par0025" class="elsevierStylePara elsevierViewall">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.</p><p id="par0030" class="elsevierStylePara elsevierViewall">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%.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Biochemical markers of neuroendocrine tumour: elevation of chromogranin A 319<span class="elsevierStyleHsp" style=""></span>ng/ml (normal of 0–100). Somatostatin, vasoactive intestinal peptide, gastrin and glucagon were normal.</p><p id="par0040" class="elsevierStylePara elsevierViewall">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.</p><p id="par0045" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">2</span></a> so it seems pertinent to communicate it in order to expand the limited information regarding its presentation, signs and therapeutic management.</p><p id="par0050" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">3</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">1</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">2</span></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.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Somatostatin analogues are the first-line treatment to control symptoms in patients with functioning gastroenteropancreatic neuroendocrine tumours.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">4</span></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"><span class="elsevierStyleSup">1</span></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"><span class="elsevierStyleSup">3</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">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"><span class="elsevierStyleSup">5</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">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. 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