Incidence and characteristics of neuroendocrine tumors in multiple endocrine neoplasia syndrome type 1

Neuroendokrini tumori rijetke su neoplazme koje nastaju malignom transformacijom neuroendokrinih stanica koje se nalaze difuzno po cijelom tijelu. Najčešća lokalizacija ovih tumora je probavni sustav. NET mogu biti funkcionalni, što znači da luče hormone i tako dovode do hipersekretornih simptoma, i nefunkcionalni. Pojavnost NET-a većinom je sporadična, ali se mogu javiti i u sklopu nasljednih sindroma, a jedan od njih je i multipla endokrina neoplazija tip 1. MEN 1 je rijetka, autosomno dominantno nasljedna bolest karakterizirana pojavom tumora paratireoidnih žlijezdi, duodenopankreatičnih NET-a te tumorima hipofize. Upravo su NET glavni uzrok smrti MEN 1 pacijenata. Cilj ovog rada je istražiti pojavnost i prikazati karakteristike NET-a u sklopu MEN 1 sindroma na pacijentima s KBC-a Zagreb pošto takva analiza još ne postoji na Hrvatskoj populaciji pacijenata s MEN 1 sindromom. Analizirani su podaci svih 11 pacijenata s MEN 1 na KBC-u Zagreb, od kojih ih je 8 razvilo NET. Podaci su prikupljeni iz bolničkog informacijskog sustava i obrađeni pomoću deskriptivne statistike. Analizirani parametri su dob i spol pacijenata, dob pri dijagnozi MEN 1 sindroma, inicijalna zahvaćenost MEN 1, postojanje HPT-a, NET-a i adenoma hipofize te dob pri dijagnozi svakog zasebno, vrsta i proširenost NET-a, provedene vrste liječenja, vrsta MEN 1 genetske mutacije i obiteljska anamneza MEN 1 sindroma. Analizom podataka utvrđeno je da je od 11 MEN 1 pacijenata, njih 6 ženskog roda (54,55%). Prosječna dob bolesnika iznosi 48 ± 14,73 godina, a medijan je 45 godina. Dijagnoza MEN 1 sindroma postavljana je prosječno sa 45,27± 15,19 godina, najranije kod pacijentice sa 18 godina, a najkasnije kod pacijentice sa 69 godina. 8 pacijenata (72,73%) razvilo je NET. Samo je 1 NET bio funkcionalni (inzulinom). 8 od 9 NET-a bilo je lokalizirano na gušterači, a 1 na duodenumu. U 3 od 8 pacijenata s NET-om, NET je bio prva manifestacija MEN 1 sindroma, a u ostalih 5 to je bio HPT. Od dijagnoze HPT-a do pojave NET-a prošlo je prosječno 7 ± 5,05 godina, s rasponom od 1 do 12 godina. U 3 pacijenta (37,5%) NET je metastazirao i kod sva 3 metastaze su bile prisutne već pri dijagnozi. Za dijagnozu NET-a najčešće korištene slikovne metode bile su MR i CT. Kirurško liječenje provedeno je za 7 NET-a, najčešća operacija bila je distalna splenopankreatektomija. Ovo istraživanje opisalo je karakteristike NET-a hrvatskih MEN 1 pacijenata i ukazalo na poklapanja i odstupanja od karakteristika drugih populacijskih studija.Neuroendocrine tumors are rare neoplasms that arise due to a malignant transformation of the neuroendocrine cells. They are most commonly located in the gastrointestinal tract. NET can be functional, meaning they secrete hormones resulting in hypersecretory syndromes, and non-functional. While most NETs are sporadic, they can also be featured in various genetic syndromes, including multiple endocrine neoplasia type 1. MEN 1 is a rare, autosomal dominantly inherited syndrome that is characterized by the occurrence of tumors in the parathyroid glands, duodenopancreatic NETs and tumors of the anterior pituitary. NETs are the main cause of death in MEN 1 patients. The purpose of this paper is to analyze the incidence and characteristics of NET in MEN 1 patients at the Clinical center Zagreb since there is no example of such research in the Croatian population of MEN 1 patients thus far. We analyzed the information of 11 MEN 1 patients diagnosed at the Clinical center Zagreb, 8 of whom developed NET. Data were collected using the hospital database and analyzed using descriptive statistics. Information that were analyzed included patients’ age, gender, age of diagnosis of MEN 1 syndrome, initial manifestation of MEN 1 syndrome, whether the patients develop HPT, NET and pituitary adenoma and age of diagnosis of each individually, type and dissemination of NET, types of treatment the patients underwent, MEN 1 mutation type and family history of MEN 1 syndrome. Results showed that out of 11 MEN 1 patients, 6 were female (54,55%). The average age of patients was 48 ± 14,73 years and the median was 45 years. Average age of MEN 1 diagnosis was 45,27± 15,19, the earliest in a patient aged 18 years old and latest in a patient aged 69 years old. 8 patients (72,73%) developed NET. Only 1 NET was functional (insulinoma). 8 out of 9 NET were located in the pancreas and 1 was in the duodenum. In 3 out of 8 NET patients, NET was the first MEN 1 manifestation, and in 5 others the first MEN 1 manifestation was HPT. The onset of NET after the diagnosis of HPT was on average 7 ± 5,05 years, ranging from 1 to 12 years. In 3 patients (37,5%), NET metastasized and in all 3 patients they were present at the time of diagnosis. The most used radiology imaging method for diagnosis of NET were MR and CT. Surgical treatment was used in therapy in 7 NETs, the most common procedure was distal splenic pancreatectomy. This paper describes the characteristics of NET in MEN 1 patients in Croatia and points out similarities and distinctions form other patient populations