Kliničke karakteristike bolesnika sa sindromom multiple endokrine neoplazije tip 1 u Hrvatskoj

master's thesis

• Title (english): Clinical characteristics of patients with multiple endocrine neoplasia syndrome type 1 in Croatia
• Author: Inga Starovečki
• Mentor: Tina Dušek (mentor)
• Committee member: Darko Kaštelan (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Tina Dušek (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2021-07-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine

Abstract

Sindrom multiple endokrine neoplazije tip 1 (MEN1) je rijetka autosomno dominantno nasljedna bolest karakterizirana razvojem primarnog hiperparatireoidizma (PHPT), adenoma hipofize i neuroendokrinog tumora (NET). Svrha istraživanja je analizirati kliničke karakteristike pacijenata sa sindromom MEN1 i istražiti korelaciju genotipa i fenotipa u ovih pacijenata. Prikupljeni su demografski i klinički podaci iz originalne medicinske dokumentacije pohranjene u bolničkom informatičkom sustavu te su obrađeni pomoću metoda deskriptivne statistike. U istraživanje je uključeno 11 pacijenata, od čega 6 ženskog spola (55%) i 5 muškog spola (45%). Ukupna prosječna dob prilikom dijagnoze MEN1 sindroma u ovih pacijenata iznosi 45.27 ± 15.19, a medijan iznosi 42 godine. Raspon dobi pri dijagnozi iznosio je od 18 do 69 godina. Genetska mutacija nađena je u 10 pacijenata (90.1%). Svi pacijenti razvili su PHPT. Prosječna dob pri dijagnozi PHPT iznosila je 42.1 ± 12.85 godina (raspon dobi od 18 do 69 godina). Najčešći oblik primjenjene terapije za PHPT bila je subtotalna paratiroidektomija. 9 od 11 pacijenata razvilo je NET sa prosječnom dobi pri dijagnozi NET 42 ± 18.83 godina (raspon dobi od 14 do 69 godina). 11% NET bilo je funkcionalno, a 89% nefunkcionalno. Najčešća lokalizacija NET-a bila je u gušterači, a najčešće primijenjen kirurški oblik liječenja bila je distalna splenopankreatektomija. U 44.4 %pacijenata s dijagnozom NET-a došlo je njegovog širenja u okolne ili udaljene organe. Adenom hipofize bio je prisutan u 5 pacijenata (45%) sa prosječnom dobi dijagnoze 43.2 ± 16 godina (raspon dobi od 13 do 57 godina). Prolaktinom (60%) i nefunkcionalni adenom (40%) bili su najčešći među dijagnosticiranim adenomima hipofize. 4 pacijenta imala su pozitivnu obiteljsku anamnezu na MEN1 sindrom što je potvrđeno genetskim testiranjem. Genetska mutacija nađena je u 10 pacijenata. Najčešća vrsta mutacije bila je supstitucija jedne aminokiseline drugom. Potrebna su dodatna istraživanja sa većim uzorkom hrvatske populacije pacijenata, koji boluju od MEN1 sindroma u svrhu poboljšanja njegove dijagnostike i liječenja.

Abstract (english)

Multiple endocrine neoplasia type 1 (MEN1) is a rare autosomal dominant syndrome characterized by the development of primary hyperparathyroidism (PHPT), pituitary adenoma and neuroendocrine tumour (NET). The goal of this paper is to analyse clinical characteristics of patients with this syndrome. Clinical and genetic analysis of eleven MEN1 patients was performed in a retrospective, single-center study. We gathered demographic and clinical information from the patients’ records from the Department of Endocrinology and Diabetology at the University Hospital Centre of Zagreb. 6 women (55%) and 5 men (45%) were included in this study. The mean patient age at diagnosis of MEN1 syndrome was 45.27 ± 15.19 (median 42y, range 18-69 y.o). Genetic mutation was detected in 10 patients (90.1%). All patients developed PHPT with mean age of onset of 42.1 ± 12.85 godina (range 18-69 y.o). The most common therapy for PHPT was subtotal parathyroidectomy. 81.8% of patients developed NET with mean age of diagnosis being 42 ± 18.83 godina (range 14-69 y.o). 11.1% of NETs were functional and 88.9% were non-functional. The most common NET location was in the pancreas and distal splenopancreatectomy the most adopted surgery in these cases. Pituitary adenoma was present in 5 patients (45%) with mean age of onset being 43.2 ± 16 godina (range 13-57 y.o). Prolactinoma (60%) and non-functioning adenoma (40%) were the most frequent among pituitary adenomas. 4 patients had a family history of MEN1 syndrome confirmed with genetic testing. Genetic mutation was found in 10 patients, the most common being point mutations, specifically substitution. Additional studies with a larger cohort of patients are necessary to describe the Croatian population of MEN1 patients altogether in order to improve diagnosis and management of the syndrome.

• Keywords: MEN1; NET; primarni hiperparatireoidizam; adenom hipofize; autosomno dominantni sindrom
• Keywords (english): MEN1; pancreatic neuroendocrine tumour; primary hyperparathyroidism; pituitary adenoma; autosomal dominant syndrome
• Language: croatian
• URN:NBN: urn:nbn:hr:105:395851
• 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: 2022-05-11 08:44:54