Multipla endokrina neoplazija u djece

master's thesis

• Title (english): Multiple endocrine neoplasia in children
• Author: Mirela Veršić
• Mentor: Nevena Krnić (mentor)
• Committee member: Katja Dumić Kubat (predsjednik povjerenstva)
• Committee member: Marija Jelušić (član povjerenstva)
• Committee member: Nevena Krnić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pediatrics); Zagreb
• Defense date and country: 2022-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Pediatrics

Abstract

Multipla endokrina neoplazija (MEN) skupina je rijetkih nasljednih sindroma koji dovode do povećanog rizika za razvoj multiplih endokrinih i neendokrinih novotvorina već u ranoj životnoj dobi. Razlikujemo dva tipa sindroma, MEN1 i MEN2, koji se razlikuju prema etiologiji i kliničkoj manifestaciji. U podlozi sindroma MEN nalaze se mutacije gena koje uzrokuju tumorigenezu. MEN1 uzrokovan je mutacijom gena MEN1, a MEN2 gena RET. Mutacije se nasljeđuju autosomno dominantno, a u dijela se bolesnika javljaju de novo. Novotvorine koje se tipično javljaju u okviru MEN1 uključuju novotvorine paratireoidnih žlijezda, duodenopankreatične neuroendokrine tumore i adenome hipofize. Medularni karcinom štitnjače najčešća je novotvorina u okviru MEN2 uz koji se javljaju i feokromocitom, novotvorine paratireoidnih žlijezda te druge neendokrine manifestacije. Uslijed raznolike kliničke prezentacije, postavljanje dijagnoze pojedinog sindroma MEN nije jednostavno te zahtijeva znanje i iskustvo liječnika, kao i dostupnost širokog spektra dijagnostičkih pretraga koje uključuju, prije svega, gensko testiranje uz mjerenje endokrinoloških i biokemijskih parametara te slikovne dijagnostičke metode. Gensko testiranje ima važnu ulogu u postavljanju dijagnoze te bi ga trebalo učiniti u svih osoba u kojih nalazimo tipičnu kliničku prezentaciju pojedinog sindroma, ali i u članova obitelji koji su pod rizikom da su nosioci mutacija. Prediktivno gensko testiranje asimptomatskih osoba s pozitivnom obiteljskom anamnezom iznimno je važno kako bi se nosioci mutacija rano otkrili te se počelo s kontinuiranim praćenjem i pravovremenim liječenjem u slučaju razvoja novotvorina. Liječenje bolesnika sa sindromom MEN često je izazovno i uključuje kiruršku resekciju novotvorina, simptomatsko liječenje uslijed hipersekrecije pojedinih hormona te druge oblike liječenja poput kemoterapije, radioterapije i liječenje ciljanim lijekovima. Zbog naravi ovih sindroma, bolesnici zahtijevaju multidisciplinarni pristup i doživotno praćenje. U diplomskom radu također smo prikazali dvije bolesnice s različitim oblicima sindroma MEN. Istaknuli smo karakteristična obilježja pojedinog sindroma koja su se javila u bolesnica, rezultate genske analize te ostalu dijagnostičku obradu, provedeno liječenje i plan praćenja.

Abstract (english)

Multiple endocrine neoplasia (MEN) is a group of rare hereditary syndromes characterized by increased risk of developing multiple endocrine and nonendocrine tumors starting from a young age. Two main types of MEN syndrome include MEN1 and MEN2, which differ in etiology and clinical presentation. MEN is caused by gene mutations that lead to tumorigenesis. MEN1 is caused by MEN1 gene mutation and MEN2 by RET gene mutation. The mutations are inherited in an autosomal dominant manner, although some patients present with de novo mutations. Tumors that typically arise in the setting of MEN1 include parathyroid tumors, duodenopancreatic neuroendocrine tumors and pituitary adenomas. The most common tumor in MEN2 patients is medullary thyroid carcinoma, but pheochromocytoma, parathyroid tumors and other nonendocrine manifestations can also occur. The clinical presentation of MEN syndromes is heterogeneous, thus making it challenging to diagnose. Making diagnosis requires clinicians’ knowledge and experience as well as a wide range of diagnostic methods that first include genetic testing accompanied by measuring various endocrine and biochemical markers and using imaging methods. Genetic testing has a significant role in confirming the diagnosis. It should be offered to individuals presenting with typical clinical manifestations of each syndrome as well as to family members that are at risk of inheriting the mutation. Prospective genetic testing in asymptomatic individuals with a positive family history is of a great importance and enables an early recognition of mutation carriers together with starting an adequate follow-up and a prompt treatment when needed. The treatment of MEN is often challenging, and it includes surgical resection of the tumors, symptomatic treatment of hormone hypersecretion in addition to other therapeutic modalities such as chemotherapy, radiotherapy, and targeted therapy. Due to the course of MEN syndromes, the patients require multidisciplinary approach and a life-long surveillance. We also presented case reports of two patients with different types of MEN syndrome. We pointed out the specifics of each syndrome type that occurred in these patients along with the results of genetic testing, remaining diagnostic work-up, treatment and further surveillance plan.

• Keywords: multipla endokrina neoplazija; djeca; novotvorine; gensko testiranje; prikaz bolesnika
• Keywords (english): multiple endocrine neoplasia; children; tumor; genetic testing; case report
• Language: croatian
• URN:NBN: urn:nbn:hr:105:750975
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-03-20 09:47:02