Diagnosis and treatment of medullary thyroid cancers

Medularni karcinom štitnjače je neuroendokrina neoplazma koja nastaje iz parafolikularnih C stanica koje proizvode hormon kalcitonin. Medularni karcinom treći je najčešći karcinom štitnjače i čini 3-5 % svih karcinoma štitnjače.Većinom se javlja sporadično, a u 25% slučajeva je genetske prirode uzrokovan mutacijom u RET protoonkogenu i javlja se u sklopu MEN sindroma, često udružen s drugim tumorima. Ukoliko se medularni karcinom javlja bez drugih endokrinih tumora naziva se familijarnim medularnim karcinomom. Sporadični oblik se manifestira kao solitarni čvor i češći je u žena srednje životne dobi. Pri postavljanju dijagnoze, polovica oboljelih već imaju pozitivne limfne čvorove. Nasljedni oblik se javlja u mlađoj životnoj dobi, češće je smješten je u gornje dvije trećine štitnjače i ima agresivniji klinički tijek. Danas se radi probir i određuje prisustvo RET mutacije među članovima obitelji oboljelih od medularnog karcinoma. U slučaju pozitivnog rezultata preporuča se učiniti profilaktičku tiroidektomiju prije 6. godine života. Najsigurnija opcija liječenja je totalna tiroidektomija s obzirom da je tumor multifokalan i bilateralan u većini pacijenata sa hereditarnim MTC-om i u 20% pacijenata sa sporadičnim tumorom. Preoperativno je potrebno izmjeriti razine katekolamina u urinu (radi isključenja feokromocitoma), kalcitonina, CEA, serumskog kalcija i PTH (radi isključenja hiperparatireoidizma), UZV vrata te CT ili MR koji mogu mogu pomoći u procjeni opsega kirurške resekcije. Uz uklanjanje štitnjače radi se i disekcija limfnih čvorova ovisno o kliničkom stadiju bolesti. Radioterapija i kemoterapija mogu imati koristi u kontroli lokalnih simptoma. Sve bolesnike s MTC-a potrebno je doživotno pratiti mjerenjem razine kalcitonina i CEA. Biološko ponašanje medularnih karcinoma može biti povoljno i pokazivati sporu progresiju i dugogodišnje preživljenje, ali tumori mogu imati brzu progresiju bolesti i tada se preživljenje mjeri u mjesecima.Medullary thyroid cancer is a neuroendocrine neoplasm that originates from parafollicular C cells which produce hormone calcitonin. Medullary carcinoma is the third most common thyroid cancer and accounts for 3-5% of all thyroid cancers. It occurs mostly sporadically, and in 25% of cases it is genetic in nature caused by a mutation in the RET protooncogene and occurs as part of MEN syndrome. When medullary cancer occurs without other endocrine tumors it is called familial medullary cancer. The sporadic form appears as a solitary node and is more common in middle-aged women. At diagnosis, half of patients already have positive lymph nodes. The hereditary form occurs at a younger age and is located in the upper two-thirds of the thyroid gland. The hereditary form is more aggressive. Today, screening determines the presence of RET mutation among family members of patients with medullary cancer. In case of a positive result, it is recommended to do a prophylactic thyroidectomy before age of 6 years. The safest treatment option is total thyroidectomy, because in most patients with hereditary MTC and in 20% of patients with sporadic form tumor is multifocal and bilateral. Urinary levels of catecholamines (to exclude pheochromocytomas), calcitonin, CEA, serum calcium, and PTH (to exclude hyperparathyroidism), CT, MR, or ultrasound of the neck should be measured preoperatively to help assess the extent of surgical resection. Lymph node dissection depends on the clinical stage of the disease. Radiotherapy and chemotherapy may be useful in controlling local symptoms. Lifelong follow- up is recommended for all patients with MTC by measuring calcitonin and CEA levels. The biological behavior of medullary cancers can show slow progression and long-term survival, but tumors may have rapid disease progression and then survival is measured in months