Endocrine Abstracts

Medullary thyroid carcinoma (MTC) is hereditary in 25 per cent of cases. This may be in association with Multiple Endocrine Neoplasia (MEN) Type 2 (A and B) or as familial MTC (FMTC) alone. The mutations causing hereditary forms of MTC arise in the RET-proto-oncogene.

A 40 yr old asymptomatic gentleman presenting with a mass in his neck. Fine needle aspiration of the mass revealed a probable medullary thyroid carcinoma. Total thyroidectomy and neck dissection was performed (confirming the diagnosis of MTC) with adjuvant radiotherapy. However, he still has radiological evidence (+ve PET and MRI scan) of metastatic disease, with a serum calcitonin of 6000 nanograms per litre (NR 0-11 nanograms per litre). Genetic analysis revealed that he was a heterozygote for the rare valine to methionine mutation at codon 804 (V804M) of the RET proto-oncogene. His 61 yr old mother and 12 yr old daughter consented to genetic testing. Both were found to be heterozygotes for the V804M mutation. His mother is asymptomatic but has elected to have a prophylactic thyroidectomy. His daughter is asymptomatic but her serum calcitonin levels are borderline high; 4.7 nanograms per litre (NR 0-4.6 nanograms per litre). The current guidelines for timing of prophylactic thyroidectomy in patients with the V804M mutation are inconclusive. After discussion she has opted for a thyroidectomy.

MTC in association with MEN 2 and FMTC is almost 100% penetrant. Non metastatic MTC is curable with total thyroidectomy. Patients with MEN 2 and FMTC will invariably die from MTC if it is untreated. It is therefore imperative to identify and treat at risk individuals. The earliest recorded case of a V804M mutation and metastatic MTC is in a 6 yr old girl. We describe a family with the rare V804M mutation illustrating the variance in penetrance and timing of MTC and suggest that all patients found to have this mutation should have a total thyroidectomy at the age of 5 years.