Medullary thyroid carcinoma--update and present management controversies.

Introduction Medullary thyroid carcinoma (MTC) is a rare thyroid malignancy arising from the parafollicular C cells. It accounts for 5-10% of thyroid malignancies and occurs in sporadic and hereditary forms. There are still many controversial aspects relating to the diagnosis and management of this unusual tumour in its various forms. The present article addresses the more important of these issues. Methods A literature review was performed using Pubmed database combined with additional original papers obtained from citations in those articles identified in the original literature search. Only those articles which related specifically to the controversial issues addressed in this review were included. Results Genetically determined tumours constitute approximately 25% of MTC and have special clinical interest because of their association with other endocrinopathies including phaeochromocytoma and hyperparathyroidism in the multiple endocrine neoplasia syndromes (MEN IIa and MEN IIb). Familial medullary thyroid carcinoma (FMTC) is a rare form not associated with any other endocrinopathies. The genetic basis for these familial tumours derives from a series of missense germline mutations in the RET protooncogene. Genetic testing by DNA analysis facilitates identification of family members at risk who can now be offered early 'prophylactic thyroidectomy' with an increased prospect of surgical success and long-term survival. MTC is a tumour which does not take up radioactive iodine, is relatively radioresistant and poorly responsive to chemotherapy. Therefore, surgery is the only treatment which can offer the prospect of cure. Total thyroidectomy with central and lateral nodal dissection can achieve biochemical cure (normocalcitonaemia) in more than 80% of cases. Compartmental orientated microdissection of cervical nodes has significantly improved the results of primary surgery but even so a group of 20% of patients will prove to have recurrent or residual disease. These cases require detailed investigation by a variety of techniques including ultrasound, cross-sectional imaging, nuclear imaging and laparoscopy with liver biopsy to exclude disseminated disease and select those patients who can be offered a prospect of cure by further neck surgery. Such an approach may be associated with successful normalisation of calcitonin levels in about 40%. Conclusions It is hoped that in the near future new medical therapies may become available to treat MTC which still has a 10-year survival of only 60-80% in spite of the application of meticulous surgical techniques.