Endocrine Abstracts

Optimal management of familial medullary thyroid cancer (MTC) involves early genetic diagnosis of affected individuals and prophylactic thyroidectomy. Patients diagnosed later may have biochemical evidence of metastases which are clinically silent. We report a family which illustrates the management difficulties which may arise with this approach. SC, a healthy 25-year-old man, presented for assessment for MTC. His mother had had a total thyroidectomy for MTC with no clinical evidence of metastases, but after surgery she had a raised calcitonin level (0.36 μg/l, normal <0.08 by RIA). Investigation has shown no definite localisation of metastases, serum calcitonin remains elevated at 169 ng/l (by ICMA), she has had no further treatment and she remains well. SC had a raised serum calcitonin level, and thyroidectomy confirmed MTC. After surgery the calcitonin remained elevated (8.8 μg/l by RIA) and he underwent bilateral neck dissection and external radiotherapy to the neck and mediastinum. He also remains well, with no clinical evidence of recurrence, but the serum calcitonin has risen over 8 years, currently 2735 ng/l (normal <18.9 ng/l by ICMA). RET proto-oncogene analysis was performed in 1999 to identify a marker for MTC in this family. No abnormality was found in exons 10 or 11, the two exons then known to harbour causative mutations. Further analysis identified a mutation in exon 15 (codon 891 TCG>GCG) in SC, his mother and his twin brother MC. This mutation was not known to be a disease marker at that time (though is now recognised as one), and careful discussion with the family was needed to explain the interpretation of this finding. MC underwent thyroidectomy, had C-cell hyperplasia and remains well with normal serum calcitonin. Other family members have been screened for the mutation; positive individuals have undergone thyroidectomy. This family highlights the issues which arise when a novel mutation, not yet recognised as a disease marker, is used to advise family members. Despite a multidisciplinary approach involving endocrinologist, surgeon, radiotherapist, geneticist and biochemist, optimal management of a patient with a raised serum calcitonin level after thyroidectomy is not clear. SC has received extensive treatment without obvious benefit, whereas his mother has had no further treatment and is well, but both have residual disease. Is there any further intervention which will help these individuals?