Medullary carcinoma of the thyroid 5% of all thyroid malignancies Arise from parafollicular `C&; cellsAssociated with MEN2A and MEN2B syndromes. RET - proto oncogene mutation is seen in familial variety.Sporadic medullary carcinoma of thyroidFamilial medullary carcinoma of thyroidPathology of medullary carcinoma of thyroidDiagnosisUnilateral50 - 60 yrs No family h/oTotal thyroidectomy with or without central node diseaseBilateralYoung ageFamily h/o + Total thyroidectomy with MRNDSheets of infiltrating neoplastic cells separated by collagen & amyloidPolygonal or spindle shaped cellsAmyloid is diagnosticIHC for calcitonin S.Calcitoninalso for follow up.FNAC- Amyloid CT/MRI in select cases.CEA is better for prognosis, Calcitonin better for follow upClinical featuresTreatmentCervical lymphadenopathy (15 to 20%) Distant blood borne metastasis to liver, bone, lung. Medullary carcinoma secretes calcitonin, carcinoma embryonic antigen (CEA), histaminases, prostaglandins E2 and F2a and serotonin. Diarrhea is seen in about 30% cases due to vasoactive intestinal peptides. Cushing's syndrome is seen in about 2 to 4% of cases due to ectopic adrenocoicotrophic hormone (ACTH). Investigate for pheochromocytoma - 24 hrs urinary VMA, catecholamines, and metanephrine. Investigate for hyperparathyroidism - serum calcium If the patient has associated pheochromocytoma operate it first to avoid hypeensive crisis during surgery for thyroid Total thyroidectomy with Bilateral central neck node dissection should be performed routinely. Tumors larger than 1.5 cm must undergo ipsilateral modified radical neck node dissection. External beam radiotherapy is controversial but is recommended for unresectable residual or recurrent tumor. No effective chemotherapy available. Prophylactic Total Thyroidectomy is indicated in RET mutation carriers. This procedure is to be done in patients before age of 6 years in MEN 2A and prior to age one in MEN 2B patients(Refer: Schwaz's Principles of surgery, 9th edition, pg no: 1367-1368)