Klinični in biokemični dejavniki, ki vplivajo na pojavnost in rast tumorjev skorje in sredice nadledvičnic

Podbregar, Ana (avtor), Jensterle Sever, Mojca (mentor)

Uvod. Incidentalomi nadledvičnic (AI) so tumorji, ki jih odkrijemo med diagnostiko ali zdravljenjem drugih kliničnih stanj, pri katerih ne sumimo na bolezen nadledvičnic. V prvem in drugem delu naloge se osredotočamo na tumorje skorje nadledvičnic – hormonsko neaktivne incidentalome nadledvičnic (NFAI) in incidentalome z avtonomnim izločanjem kortizola (MACE), v tretjem delu na tumorje sredice nadledvičnic – feokromocitome (FEO) in paragangliome (PGL) ter hormonsko aktivnost sredice nadledvičnic. Z raziskovalnim delom smo želeli osvetliti vpliv izbranih kliničnih značilnostih in dejavnikov, ki vplivajo na pojavnost, rast in hormonsko aktivnost teh tumorjev. Hipoteze. Raziskovalno delo sestavljajo trije medsebojno povezani deli. V prvem delu smo raziskali povezavo med pojavnostjo AI in indeksom telesne mase (ITM). V drugem delu smo preverili ali izhodiščni ITM vpliva na rast in pojav hormonske aktivnosti NFAI po dolgotrajnem sledenju. V tretjem delu smo primerjali pojavnost FEO in/ali PGL pri bolnikih s cianotično prirojeno srčno napako (PSN) s pojavnostjo pri bolnikih z acianotično PSN in preverjali ali je pojavnost PGL in/ali FEO povezana s kroničnim hipoksičnim stresom. Metode. V prvem delu smo izvedli retrospektivno analizo skupine preiskovancev, hospitaliziranih zaradi AI od januarja 2005 do januarja 2012. V drugi delu smo opravili 10-letno longitudinalno opazovalno raziskavo, v katero smo vključili 67 preiskovancev iz prvega dela. V tretjem delu smo v presečni raziskavi primerjali bolnike s cianotično in acianotično PSN. Rezultati. V prvem delu smo identificirali 290 preiskovancev z NFAI in 142 z MACE. Prevalenca AI, NFAI in MACE je bila pri preiskovancih z debelostjo in prekomerno težo v primerjavi z osebami z normalno telesno težo za 68–87 % večja v vseh starostnih skupinah. V drugem delu se je v 10.5 (9.1–11.9) letih spremljanja pri 15 (22.4 %) od 67 preiskovancev iz NFAI razvil MACE (p < 0.001). Incidenca napredovanja v hormonski aktivnosti je bila pri preiskovancih s prekomerno telesno težo in debelostjo znatno večja kot pri preiskovancih z izhodiščnim ITM < 25 kg/m2 (p = 0.016 v obeh skupinah z ITM > 25 kg/m2). Razvoj hormonske aktivnosti NFAI je bil pogostejši pri NFAI, ki imajo izhodiščne vrednosti kortizola po 1 miligramskem deksametazonskem testu (DMT) več kot 30 nmol/L. Rast NFAI smo beležili pri 38 (56.7 %) preiskovancih, klinično pomembno povečanje tumorja (? 10 mm) pri 6 preiskovancih (8.9 %). Pomembne korelacije med rastjo tumorja (NFAI) in izhodiščno velikostjo ali ITM nismo ugotavljali (p > 0,05). Statistično značilne povezave med inzulinsko rezistenco, izmerjeno z ocena homeostatske inzulinske rezistence HOMAIR, in velikostjo tumorja nismo ugotavljali (? = -0.079, p = 0.561). Statistično značilne povezave med obsegom pasu in velikostjo tumorja nismo ugotavljali (? = -0.052, p = 0.728). V tretjem delu smo pri bolnikih s cianotično PSN ugotavljali statistično značilno višje vrednosti normetanefrina v plazmi (p = 0.002) v primerjavi z bolniki z acianotično PSN. S korelacijsko analizo smo potrdili povezanost med vrednostjo normetanefrina v plazmi in proBNP (? = 0.449, p = 0.002) ter saturacijo (? = -0.444, p = 0.003). Zaključki. Dokazali smo pozitivno povezanost pojavnosti tumorjev nadledvičnic in višjega ITM, tako pri NFAI in MACE. Ugotovili smo, da ITM preiskovalncev ob prezentaciji NFAI ne vpliva na rast tumorja skorje nadledvičnic in da je višji ITM ob odkritju NFAI povezan z večjo verjetnostjo za razvoj avtonomne glukokortikoidne aktivnosti AI (MACE) v 10-letnem opazovalnem obdobju. Dodatno smo ugotovili, da je napredovanje v hormonski aktivnosti pogostejše pri izhodiščnih vrednostih kortizola po 1 miligramskem DMT > 30 nmol/L. Inzulinska rezistenca, izmerjena s HOMAIR in obseg pasu nista bili povezani z velikostjo tumorja. Aktivnost sredice nadledvičnice in/ali PGL pri bolnikih s cianotično PSN je bila značilno večja kot pri bolnikih z acianotično PSN. Statistično značilna je bila povezanost plazemskih vrednosti normetanefrina in saturacije ter proBNP.

• Jezik: Slovenski jezik
• Ključne besede: incidentalom nadledvičnice, hormonsko neaktiven incidentalom nadledvičnic, incidentalomi z avtonomnim izločanjem kortizola, feokormocitom, paragangliom
• Vrsta gradiva: Doktorsko delo/naloga
• Organizacija: MF - Medicinska fakulteta
• Leto izida: 2021
• PID: 20.500.12556/RUL-127694
• COBISS.SI-ID: 66996739
• Datum objave v RUL: 20.06.2021

PODBREGAR, Ana, 2021, Klinični in biokemični dejavniki, ki vplivajo na pojavnost in rast tumorjev skorje in sredice nadledvičnic [na spletu]. Doktorska disertacija. [Dostopano 19 maj 2025]. Pridobljeno s: https://repozitorij.uni-lj.si/IzpisGradiva.php?lang=slv&id=127694

Sekundarni jezik

• Jezik: Angleški jezik
• Naslov: Clinical and biochemical factors affecting adrenal cortex and adrenal medulla tumor incidence and growth

Izvleček

Introduction. Adrenal incidentalomas (AI) are adrenal tumors detected by diagnostic imaging not performed for suspected adrenal disease. In the first and the second part of the thesis we focus on the tumors of adrenal cortex – nonfunctional adrenal incidentaloma (NFAI) and adenomas with mild autonomous cortisol excess (MACE), in the third part to the tumors of adrenal medulla – pheochromocytomas (PHEO) and paragangliomas (PGL) and hormonal activity of the adrenal medulla. The aim of the research work was to evaluate the impact of selected clinical features and parametrs influencing the prevalence, growth and hormonal activity of these tumors. Hypotheses. The research work consists of three interrelated parts. In the first part we investigated the association between the incidence of AI and body mass index (BMI). In the second part we examined whether basline BMI of participants affects the growth and occurrence of hormonal activity of NFAI after long term follow up. In the third part we compared the incidence of PHEO and/or PGL in patients with cyanotic congenital heart defect (CHD) with the incidence in patients with acyanotic CHD and examined whether the incidence of PGL and/or PHEO was associated with chronic hypoxic stress. Methods. In the first part we conducted a retrospective study including participants hospitalized because of AI from January 2005 to January 2012. In the second part we conducted a 10-year longitudinal observational study, in which we included 67 subjects from the first part. In the third part we compared patients with cyanotic and acyanotic CHD in a cross-sectional study. Results. In the first part 290 subjects with NFAI and 142 with MACE were identified. The prevalence of AI, including NFAI and MACE was 68-87 % higher in subjects with obesity and overweight compared to subjects with normal body weight across all age groups. In the second part 15 (22.4 %) out of 67 subjects with NFAI developed MACE (p < 0.001) in 10.5 (9.1–11.9) years of follow-up. The incidence of progression was significantly higher in subjects with overweight and obesity than in subjects with baseline BMI < 25 kg/m2 (p = 0.016 in both groups with BMI > 25 kg/m2). The development of NFAI hormonal activity was more common in NFAIs, with baseline cortisol levels after 1 milligram dexamethasone test (DST) of more than 30 nmol/L. An increase in NFAI was recorded in 38 (56.7 %) subjects, a clinically significant increase in tumor size (䁥 10 mm) in 6 subjects (8.9 %). No significant correlations were observed between tumor growth (NFAI) and baseline size or BMI (p > 0.05). No statistically significant association between Homeostatic model assessment for insulin resistance (HOMAIR) and tumor size was found (ρ = -0.079, p = 0.561). No statistically significant association between waist circumference and tumor size was found (ρ = -0.052, p = 0.728). In the third part statistically significantly higher plasma levels of normetanephrine (p = 0.002) were observed in patients with cyanotic CHD compared to patients with acyanotic CHD. Correlation analysis confirmed the association between normetanephrine plasma levels and proBNP (ρ = 0.449, p = 0.002) and saturation (ρ = -0.444, p = 0.003). Conclusions. We demonstrated a positive association between the incidence of adrenal tumors and higher BMI in NFAI and MACE. We found that BMI of participants at the time of NFAI presentation did not affect adrenal cortex tumor growth and that higher baseline BMI was associated with higher probability for the development of autonomic glucocorticoid AI activity (MACE) over a 10-year observational period. In addition, progress was found to be more frequent when baseline cortisol levels after a 1 mg DST was > 30 nmol/L. Insulin resistance measured by HOMAIR and waist circumference were not related to tumor size. Hormonal activity of adrenal medulla and/or PGL were significantly higher in patients with cyanotic CHD than patients with acyanotic CHD. The association between normetanephrine plasma levels and saturation and proBNP was statistically significant.

• Ključne besede: adrenal incidentaloma, nonfunctional adrenal incidentaloma, adenomas causing mild autonomous cortisol excess, pheochromocytoma, paraganglioma