Purpose: Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease, characterized by germ-line mutations in the RET proto-oncogene, mainly in exons 10 and 11, but also in exons 13, 14 and 15. Activating germ-line mutations in the RET proto-oncogene cause the development of familial medullary thyroid carcinoma (FMTC) or medullary thyroid carcinoma (MTC) as a part of multiple endocrine neoplasia type 2 syndrome (MEN2).
Methods: The 1st patient, women 52 years old and mother of son, 32 years old, firstly visited endocrinologist for a goitre in right lobe in 2007. In October, 2008 she underwent total thyroidectomy with regional lymph node dissection for a palpable enlarged lymph node on the right side of neck. Histologically, the neoplasm exhibited invasive growth in the capsule and surrounding thyroid tissue. The diagnosis of MTC was confirmed with the subsequently investigated high basal and stimulated calcitonin levels (intravenous injection of calcium 2.53 mg/kg of body weight together with subcutaneous injection of pentagastrin 57 μg per kilogram of body weight). In January, 2009 123I-mIBG (metaiodobenzylguanidine) scintigraphy showed normal accumulation.
The son of this patient, 32-year-old man, was examined, too. He had slightly normal basal but increased of stimulated plasma calcitonin levels. Neck ultrasound was performed with normal results. We tested for RET germ-line mutations both of patients in exons 10, 11, 13, 14, 15 and 16. Direct fluorescent sequencing of genomic DNA revealed heterozygous mutation in the RET proto-oncogene in the exon 13 in both tested persons.
In March, 2009 he underwent total thyroidectomy. C-cell hyperplasia features were present in the operated thyroid tissue. The postoperative basal calcitonin level was normal, but stimulated calcitonin level were slightly increased (500 pg/ml).
The diagnostic scintigraphy with 123-mIBG were performed and the liver metastases were found. In June, 2009 the therapy with 3.7 GBq 131I-mIBG was performed. After therapy the calcitonin level goes down (100 pg/ml). Next treatment is properted after 4 months.
Conclusion: The therapy 3.7 GBq 131I-mIBG was performed in patient, where germ-line mutation was detected due to the systematic genetic screening of the RET proto-oncogene, which is useful for genetic counselling of potential risk of MTC in other family members.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology