Endocrine Abstracts

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumour of the parafollicular cells of the thyroid gland accounting for 5–15% of thyroid carcinomas. Most medullary thyroid carcinomas occur sporadic while up to 25% are familial as part of the multiple endocrine neoplasia type 2 (MEN-2). Most of the carcinomas have already metastasized at the time of detection. Surgical therapy is the treatment of choice in patients with MTC, both for patients with the familial and the sporadic form. All patients should be tested to verify or exclude mutations in the RET-Protooncogene (MEN-2 disease). Total thyroidectomy in affected members of kindreds with MEN-2 is able to prevent or cure medullary thyroid carcinoma. Persistent or recurrent disease is defined by a pathologic pentagastrin stimulation test performed after primary surgery.

In case of recurrent or metastatic disease surgical therapy is useful but normalisation of calcitonin can be expected only in 25% of the cases. Different new strategies in the treatment of MTC are under investigation. Vaccination with calcitonin and/or CEA peptide-pulsed dendritic cells C results in the induction of a cellular, antigen-specific immune response in patients with MTC, leading to clinical response in some patients.

As most MTC’s are not sensitive to chemotherapy, new therapy strategies could include the use of COX-2 inhibitors to sensitize MTC cells for cytotoxic effects of drugs such as doxorubicin via reducing the expression and function of the permeability glycoprotein (P-gp) regulated by the multidrug resistance 1 (MDR1) gene.

Experimental data demonstrate the effect of radioiodine therapy of MTC after tissue-specific sodium-iodide-symporter (NIS) gene transfer to MTC cells using the calcitonin promoter gene. Other approaches include the use of humanized anti-CEA antibodies in combination with chemotherapy, adenovirus-mediated tumour-specific combined gene therapy, the use of tyrosine kinase inhibitor therapy and in somatostatin-receptor positive tumours the use of radiolabeled somatostatin analogues.