Medullary and non-medullary thyroid cancer in a family

We report an unusual family which suggests that susceptibility to medullary and non-medullary thyroid cancer (MTC, NMTC) may be related. The index case, a woman aged 59, presented with a 3 cm nodule in the right lobe of her thyroid gland. Thyroid function tests were within normal limits. The patient’s past medical history was unremarkable. Furthermore, she was normotensive and had no clinical features suggestive of Cowden’s disease. Ultrasound examination showed the thyroid lesion was solid and a biopsy was diagnostic of a diagnosis of MTC. The patient underwent a right lobectomy of the thyroid gland with complete excision of isthmus, histology confirming the biopsy diagnosis. Her sons, aged 39 and 35 years, underwent screening for C-cell hyperplasia. Both had repeated exaggerated response to pentagastrin stimulation displaying more than 20-fold increases in circulating calcitonin. In addition each had normal thyroid function, and was normotensive with normal 24 h urinary catecholamine levels. There was no history of radiation exposure in either the mother or her two sons. Using venous blood as a source of DNA the index case was screened for a germline mutation in RET. This analysis showed that the index case possessed the V804L mutation within exon 14 that has been implicated as a cause of MEN-2A, MEN-2B and FMTC