A patient with a metastatic gastroenteropancreatic endocrine carcinoma causing hyperinsulinaemic hypoglycaemia and the carcinoid syndrome

Abstract

We present the case of a 57-year-old patient who initially presented with a constellation of symptoms including intense pruritis, flushing and diarrhoea. Following several months clinical deterioration, the patient was investigated radiologically, where multiple hepatic tumours were identified. Liver biopsy confirmed the presence of a well-differentiated metastatic gastroenteropancreatic endocrine carcinoma with biochemical evidence of serotonin secretion. Over a period of six months, the clinical course of the patient's disease progressed whereby severe hypoglycaemia became the major manifestation. Subsequent biochemical investigations confirmed the diagnosis of an insulinoma. Extensive radiological investigation revealed a solitary primary pancreatic tumour, indicating the presence of a metastatic pancreatic endocrine tumour (PET) secreting both insulin and serotonin. The patient was treated with a chemotherapy regimen consisting of 12 cycles of 5-fluorouracil/oxaliplatin, responding clinically -improved World Health Organization performance score from 3 to 1, biochemically -significantly reduced plasma chromogranin A and cancer antigen 19-9 concentrations and improved liver function tests, and radiologically -reduced pancreatic and hepatic tumour size. This is the first report of a primary PET secreting insulin and serotonin. Due to the association of serotonin-secreting gastroenteropancreatic endocrine tumours (GEP-ETs) with multiple endocrine neoplasia type-1 (MEN1) and biochemical evidence of an insulinoma, MEN1 should also be considered in such cases. The case provides further evidence for the biological heterogeneity of GEP-ETs and the myriad secretory humoral products and resultant clinical syndromes arising from such tumours.

Incidence and prognostic value of serotonin secretion in pancreatic neuroendocrine tumours

“…A review of literature reveals a very limited number of PNET cases with serotonin secretion in combination with other hormones . Here, we report two patients with cosecretion or consecutive secretion of insulin and serotonin and one patient with cosecretion of gastrin and serotonin.…”

“…A review of literature reveals a very limited number of PNET cases with serotonin secretion in combination with other hormones. 29,30 Here, we report two patients with cosecretion or consecutive secretion of insulin and serotonin and one patient with cosecretion of gastrin and serotonin. These patients did not have symptoms of the carcinoid syndrome and again these patients had stage 4 disease with a very high serum CgA levels of more than 20 times ULN.…”

Intractable hypoglycaemia in a patient with advanced carcinoid syndrome successfully treated with hepatic embolization

“…Our case demonstrates that with disease progression in metastatic pNETs it is often not possible to The cause of the recurrent hypoglycaemia in our patient is likely to relate to the development of inappropriate insulin co-secretion from his NET (as previously described 2 ) and/or depletion of his hepatic glycogen stores as the disease evolved, but, unfortunately, insulin and C-peptide were not measured. Hypoglycaemia due to glucagon-like peptide 1 (GLP-1) secretion has also been reported in a patient with a strumal ovarian carcinoid syndrome; co-secretion of somatostatin by the same tumour meant that the patient was also suffering with (predominantly fasting) hyperglycaemia.…”

“…Hypoglycaemia in the context of metastatic pNETs is due to either functional transformation of the tumour 2 or, alternatively, to depletion of hepatic glycogen stores with extensive hepatic metastases. The usual treatment algorithm for hypoglycaemia in such instances includes the use of dietary manipulation, diazoxide and SA.…”

Metastatic Insulinoma in a 16-Year-Old Adolescent Male With Men-1: A Case Report and Review of the Literature

“…Multiple endocrine neoplasia type 1 (MEN-1) is an autosomal dominant condition associated with various combinations of 3 groups of endocrine tumors: (1) parathyroid adenomas (most common of all endocrine tumors in MEN-1), (2) pituitary tumors, including prolactinoma (most common of all pituitary tumors in MEN-1), acromegaly, Cushing disease, and (3) gastro-entero-pancreatic tumors such as gastrinoma, insulinoma, and glucagonoma, and nonendocrine tumors, including carcinoid, facial angiofibroma, lipoma, meningioma, ependymoma, and leiomyoma (1)(2)(3). Clinical diagnostic criteria for MEN-1 include presence of at least 2 of the 3 groups of endocrine tumors as listed above (1). Insulinomas are rare endocrine tumors in the pediatric age group and may be associated with MEN-1 in 10% of cases (2).…”