Carcinogenic hypergastrinemia: signet-ring cell carcinoma in a patient with multiple endocrine neoplasia type 1 with Zollinger-Ellison's syndrome.

CONTEXT: Gastric neuroendocrine tumors are rare neoplasms that originate from gastric enterochromaffin-like (ECL) cells in the oxyntic mucosa. Gastrin and its derivates have been reported to regulate epithelial cell proliferation, migration, and differentiation. Mutations in the epithelial cadherin (E-cadherin) gene have been shown to be associated with the occurrence of diffuse gastric carcinomas in affected families. OBJECTIVE: In this study we investigated the histopathological and molecular findings in the gastrointestinal wall of a patient with multiple endocrine neoplasia type 1 with malignant duodenal gastrinoma and multiple gastric ECL cell tumors, who additionally developed a signet-ring cell carcinoma of the stomach. DESIGN AND PATIENT: Biopsies from the gastrointestinal tract of a patient with multiple endocrine neoplasia type 1 were immunostained for vesicular monoamine transporter-2 and E-cadherin. Nonamidated gastrin products were measured in the serum of the patient using antibodies that react with progastrin, Gly-extended, and amidated gastrins. Genetic analyses were performed to exclude germ-line mutations within the E-cadherin gene. RESULTS: Immunohistochemical studies of gastric ECL cell tumors showed a largely diminished E-cadherin expression in comparison to gastric surface mucosa cells and a loss of E-cadherin expression in the cells of the signet-ring carcinoma. Detailed biochemical measurements revealed progastrin concentrations that were approximately 20%, and Gly-gastrin concentrations that were approximately 10% the amidated gastrin concentrations in plasma. Molecular analyses revealed no E-cadherin germ-line mutation. CONCLUSION: Our immunohistochemical studies might suggest that the gastrinoma-associated excessive progastrin tissue concentrations led to diminished expression of E-cadherin within the gastric mucosa and promoted tumor development of a signet-ring cell carcinoma.

Serum selenium levels in patients with remission and relapse of graves' disease.

OBJECTIVE: Selenium (Se) in the form of selenocysteine is an essential component of the family of the detoxifying enzymes glutathione peroxidase (Gpx) and of the iodothyronine selenodeiodinases that catalyze the extrathyroidal production of tri-iodothyronine (T(3)). Thus, Se deficiency may seriously influence the generation of free radicals, the conversion of thyroxine (T(4)) to T(3) and a thyroidal autoimmune process. The aim of this study was to investigate whether serum Se levels may influence the outcome of Graves' disease (GD). DESIGN AND METHODS: 83 patients (77 women, 6 men) with active GD were retrospectively analyzed (mean age 40,0 years). Twenty-four GD patients went into remission and were euthyroid during follow-up (median follow-up: 20.1 months), whereas 59 patients did not go into remission or developed relapse over the following 24 months. TSH receptor autoantibodies (TRAb) were measured using the second generation assay on the basis of human TSH receptor. Se levels were determined at the first visit in our outpatient clinic and were correlated with TRAb levels and clinical outcome of these patients. RESULTS: Median TRAb levels in the group of remission were significantly (p<0.0001) lower than TRAb values in the relapse group (2.1 as compared to 8.6 IU/l). By comparing mean serum Se levels in the remission and relapse group no significant differences were seen (73.0 vs. 71.7 microg/l). Detailed analyses of both groups of patients, however, revealed that highest serum Se levels (>120 microg/l) were seen in the remission group, indicating a positive effect of Se levels on the outcome of GD. In addition, we also compared these results with TRAb levels of these patients. We could show that TRAb levels and serum Se values were positively correlated in the relapse group, whereas a negative correlation of both parameters were seen in the remission group, supporting the idea of a positive effect of Se on thyroidal autoimmune process. CONCLUSION: Our data indicate that high serum Se levels (>120 microg/l) may influence the outcome of GD. This is important, as Se administration trials in GD, which are under discussion need to be performed with Se supplementation at higher dosages than used in autoimmune thyroiditis.

Identification of occult metastases of medullary thyroid carcinoma by pentagastrin-stimulated intravenous calcitonin sampling followed by targeted surgery.

BACKGROUND: High calcitonin (CT) serum levels suggest metastatic spread in medullary thyroid carcinoma (MTC) after thyroidectomy. In limited disease stages, however, morphological investigations including ultrasound, magnetic resonance imaging (MRI) and 18F-FDG positron emission tomography ([18F]FDG-PET) may often fail to identify exact tumour sites. OBJECTIVE: The aim of the present study was to establish an improved strategy to identify small cervical tumours by combining pentagastrin stimulation with bilateral cervical intravenous CT sampling followed by high-resolution ultrasound. DESIGN AND PATIENTS: Six MTC patients were examined, of whom five patients already had bilateral neck dissection. Five patients had sporadic MTC, and one patient suffered from MEN2a. RESULTS: Retrospective analysis of all patients revealed a highly sensitive positive correlation between an early calcitonin peak (20-40 s after pentagastrin injection) and site of cervical tumour affection. Postinterventional ultrasound examination of the affected regions of the neck revealed suspicious presence; in some cases small lymph nodes of less than 1 cm in size were then surgically excised. On histology, small tumours could be identified in four patients. Postsurgical examination revealed a clear decline of basal serum calcitonin levels in four patients (between -41% and -100%). In two patients CT normalized to baseline levels (< 10 pg/ml) and in another two patients CT rendered to near normal (14 and 17 pg/ml). CONCLUSION: Pentagastrin stimulation-based intravenous catheter sampling may be beneficial in the diagnostic work-up of MTC after thyroidectomy. Our data show that an early calcitonin peak (20-40 s after administration of pentagastrin) helps to identify tumour-affected regions.