1. Medullary Carcinoma of the Thyroid Karl Rice

2. Causes Diagnosis and Treatment Medullary thyroid carcinoma originates from the parafollicular cells (C cells) Genetic factor is a major cause. RET proto-oncogene. Familial vs. Sporadic MTC. First characterised in 1959.

3. Diagnosis Markers used Calcitonin Carcinoembryonic antigen – CEA Less sensitive Less variation

4. Genetic diagnosis. Caused by changes in the RET proto-oncogene located on Chromosome 10. Mutated RTK – RET What is RET involved in? Regulation of cell growth/ development. Its mutation – Familial MTC, Hyperparathyroidism, Pheochromocytoma.

5. Intro to Treatment Familial MTC – Autosomal dominant trait. DNA analysis has made it possible to identify who carries the mutant gene. Surgical removal can be curative. Note: Removal of MTC tumours vs. Parathyroid tumours and Pheochromocytomas.

6. Treatment Surgical Radiation – external beam radiotherapy No Role - Radioiodine Protein kinase inhibitors – Clinical trials! Response, small reduction. Durable – 3 years. Major side effects Vandetanib – Caprelsa – April 2011.

7. Recent studies carried out on the matter (1) Feb 2014 – F-18 FDG-PET-CT in the diagnostic of a late medullary thyroid carcinoma recurrence in a patient with follicular-papillary thyroid cancer. Misdiagnosis at initial stage Increased need for special attention to the unusual, sometimes harder to detect forms.

8. Questions we need to ask ourselves based on this study? 1.Is it necessary to have a routinely extensive immunohistochemical profile on histological specimens? 2.Should we always do calcitonin in any patient with thyroid carcinoma? 3.Should we perform calcitonin on a routine basis in DTC? 4.If serum calcitonin is abnormal but in dynamic decreasing, most suitable therapeutic decision?

9. Conclusion of this study! Routinely extensive immunohistological exams! If this is not possible It is recommended to check the -Serum calcitonin ** -Different histological profiles *

10. Serum calcitonin in minimal residual/ recurrent MTC? (2) These patients require calcitonin stimulation to show the presence of malignancy as the amount of cancer cells present isn't vast enough to push the calcitonin past undetectable levels. The stimulating agents used in a study in AHEPA hospital in Greece were calcium glucagonate and pentagastrin. What's the benefit?

11. The ethical question – animal testing?(3) 1997 – National academy of science, USA. Development of medullary thyroid carcinoma in transgenic mice expressing the RET proto- oncogene altered by a multiple endocrine neoplasia type 2A mutation Bread transgenic mice with familial MTC gene.

12. References 1.Doina Piciu and Andra Piciu. F-18 FDG-PET-CT in the diagnostic of a late medullary thyroid carcinoma recurrence in a patient with follicular-papillary thyroid cancer. Case reports in endocrinology 2014; 2014(): 4 pages. 2.Vainas I, Marthopoulous A, Chrisoulidou A, Raptou K, Tziomalos K, Pazaitou-Panayiotou K. Calcitonin stimulation tests for the early diagnosis and follow-up of patients with C cell disease; a descriptive analysis. Hippokratia 2013; 17(3): 246-251. 3.Michiels F-M et al. Development of medullary thyroid carcinoma in transgenic mice expressing the RET proto-oncogene altered by a multiple endocrine neoplasia type 2A mutation. Proc. Natl. Acad. Sci. USA 1997; 94(): 3330-3335.