Introduction: Previous studies have shown that the G691S and S904S variants of RET proto-oncogene are associated with Multiple Endocrine Neoplasia (MEN) 2A syndrome and have a modifier effect on the age of onset. They are also associated with Papillary Thyroid Carcinoma and with Pheochromocytoma without Medullary Thyroid Carcinoma (MTC). Nevertheless, the influence of these polymorphisms on cases of sporadic MTC is still unclear. We present a patient with sporadic Medullary Microcarcinoma with polymorphisms in RET proto-oncogene.
Methods: A 56 year-old-male with a mild increase of Calcitonin levels (CT:26.3 pg/ml <10) was admitted to the outpatient Endocrinological Clinic for further evaluation. TPO and Tg antibodies were negative and CEA was within normal range. He had a history of congenital cryptorchidism and hypercholesterolemia. Family history for MTC was negative. A Calcium stimulation test was performed, which showed an increase of CT levels up to 637 pg/ml in 2 minutes. Thyroid sonography was normal (without Hashimoto thyroiditis or any nodules). Total thyroidectomy was performed.
Results: The histology of the thyroid gland showed a Micro-Medullary Carcinoma, 1 mm diameter with positive Chromogranin and Synaptophysin staining along with bilobar diffuse and nodular C-cell hyperplasia. RET oncogene analysis was performed and showed two polymorphisms, in exon 11 G691S and in exon 15 S904S of RET proto-oncogene.
Conclusion: Polymorphisms in RET proto-oncogene are rare. Further studies are needed in order to confirm a possible association of polymorphisms of RET proto-oncogene in sporadic MTC.
18 - 21 May 2019
European Society of Endocrinology