Utjecaj remisije Cushingova sindroma na parametre metaboličkoga sindroma

doctoral thesis

• Title (english): Influence of remission of Cushing's syndrome on parameters of metabolic syndrome
• Author: Annemarie Balaško
• Mentor: Tina Dušek (mentor)
• Committee member: Lea Smirčić-Duvnjak (predsjednik povjerenstva)
• Committee member: Matias Trbušić (član povjerenstva)
• Committee member: Ivan Pećin (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2024-05-02, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Universal decimal classification (UDC): 616 - Pathology. Clinical medicine

Abstract

Cilj ovog istraživanja bio je ispitivanje promjene metaboličkih parametara u bolesnika s Cushingovim sindromom prije i nakon liječenja, odnosno ispitivanje utjecaja remisije bolesti na pojedine komponente metaboličkog sindroma te pridružene bolesti. Dodatni cilj bio je analizirati razlike između ACTH-ovisnog i ACTH-neovisnog CS, pojavnost kardiovaskularnih i tromboembolijskih događaja, učinak remisije na kardiovaskularni rizik, kvalitetu života te oporavak osovine hipotalamus-hipofiza-nadbubrežna žlijezda. U istraživanje je uključeno 78 bolesnika liječenih u Zavodu za endokrinologiju KBC Zagreb zbog prekomjernog lučenja kortizola uzrokovanog ACTH-ovisnim ili ACTH-neovisnim Cushingovim sindromom u periodu od 2011. do 2017. god. Medijan dobi ispitanika bio je 46 godina, a 83,3% ispitanika su bile žene. Najčešće se radilo o ACTH-ovisnom CS ili Cushingovoj bolesti u 69,2% bolesnika.
Najčešće pridružene bolesti u ispitivanoj skupini su bile: arterijska hipertenzija (76,9%), hiperlipidemija (46,2%), pretilost (42%) te šećerna bolest (32%) i njihova pojavnost bila je značajno veća nego u općoj populaciji. Nakon operativnog liječenja je 87,2% bolesnika postiglo remisiju bolesti. Udio bolesnika u remisiji u ACTH-ovisnoj skupini iznosio je 81,5%, a u ACTH-neovisnoj skupini 100%. Šest mjeseci nakon postizanja remisije bolesti došlo je do značajnog smanjenja odnosno poboljšanja glukoze u plazmi (p=0,001), HbA1c (p=0,007), ukupnog kolesterola (p=0,032), HDL kolesterola (p=0,001) dok smanjenje vrijednosti LDL kolesterola i triglicerida nije doseglo razinu statističke značajnosti. Također je došlo do značajnog smanjenja pojavnosti šećerne bolesti uz nesignifikantno smanjenje pojavnosti arterijske hipertenzije, debljine i hiperlipidemije za ukupnu populaciju. Međutim kada se gledala razlika između ACTH-ovisnog i ACTH-neovisnog CS nađena je značajna razlika u svim odrednicama metaboličkog sindroma šest mjeseci nakon remisije. Također su bolesnici u remisiji imali statistički značajno smanjenje kardiovaskularnog rizika iz umjerenog u graničan rizik u usporedbi s bolesnicima s aktivnom bolesti (p=0,009).
Što se tiče kvalitete života prije operacije su bolesnici s ACTH-ovisnim CS imali bolju pokretljivost (p=0,016), bolje skrbili o sebi (p=0,014) te bolje izvršavali uobičajene aktivnosti (p=0,026) u odnosu na bolesnike s ACTH-neovisnim CS. U remisiji nije bila značajna razlika u parametrima kvalitete života izuzev granične značajnosti za uobičajenu aktivnost u korist ACTH-ovisnog CS (p=0,059). Vrijeme oporavka osovine hipotalamus-hipofiza-nadbubrežna žlijezda bila je duža u bolesnika s ACTH-neovisnom CS međutim bez statističke značajnosti (p=0,172).
Na temelju ovog istraživanja možemo zaključiti da remisija CS dovodi do značajnog smanjenja opsega struka te bolje regulacije krvnog tlaka i glikemije kao i do smanjenja koncentracije ukupnog kolesterola i HDL kolesterola, međutim ne dovodi do značajne promjene u koncentraciji LDL kolesterola i triglicerida. Procjenjujući kardiovaskularni rizik pomoću Heart risk kalkulatora, remisija CS dovodi do značajnog smanjenja kardiovaskularnog rizika u odnosu na rizik za vrijeme trajanja aktivne bolesti.

Abstract (english)

This study aimed to investigate the changes in metabolic parameters in patients with Cushing's syndrome before and after treatment, especially the influence of disease remission on each component of the metabolic syndrome and its associated comorbidities. An additional purpose of the study was to investigate the differences between ACTH-dependent and ACTH-independent CS, the occurrence of cardiovascular and thromboembolic events, the influence of remission on cardiovascular risk assessment, quality of life, and the recovery of the hypothalamic-pituitary-adrenal axis (HPA). The study comprised 78 patients treated for ACTH-dependent and ACTH-independent Cushing's syndrome in the period from 2011 to 2017 at the Department of Endocrinology, University Hospital Center Zagreb. The median age was 46 years and 83.3% of the patients were female. ACTH-dependent CS was present in 69,2% of the patients.
The most common comorbidities in our cohort included arterial hypertension (76,9%), hyperlipidemia (46,2%), obesity (42%), and diabetes (32%) which was more common than in the general population.
After surgical treatment 87,2% of the patients achieved remission. Patients with ACTH-dependent CS achieved remission in 81,5% of the cases compared to 100% in patients with ACTH-independent CS. Six months after remission there was a significant change and improvement of glucose levels in the blood (p=0,001), HbA1c levels (p=0,007), total cholesterol (p=0,032), and HDL cholesterol levels (p=0,001) whereas levels of LDL cholesterol and triglycerides did not achieve statistical significance. Among the general cohort, there was a significant decrease in the incidence of diabetes and a nonsignificant decrease in hypertension, obesity, and hyperlipidemia.
Comparing ACTH-dependent and ACTH-independent CS six months after remission there was a significant decrease of all comorbidities. There was also a significant decrease in cardiovascular risk calculating heart risk score (p=0.009). Quality of life did not change significantly after remission except for borderline significant improvement of usual activities in the ACTH-dependent CS cohort (p=0,059).
HPA-axis recovery was longer in the ACTH-independent CS cohort but without statistical significance (p=0,172). We can conclude that remission of CS leads to a significant reduction in waist circumference and better regulation of blood pressure and glycemia, as well as to a decrease in the concentration of total cholesterol and HDL cholesterol, however, it does not lead to a significant change in the concentration of LDL cholesterol and triglycerides. Assessing cardiovascular risk using the Heart risk calculator, CS remission leads to a significant reduction in cardiovascular risk compared to the risk during active disease.

• Keywords: Cushingov sindrom; ACTH-ovisan; ACTH-neovisan; remisija; metabolički parametri; kardiovaskularni rizik; kvaliteta života
• Keywords (english): Cushing's syndrome; ACTH-dependent; ACTH-independent; remission; metabolic parameters; cardiovascular risk; quality of life
• Language: croatian
• URN:NBN: urn:nbn:hr:105:175067
• Study programme: Title: Biomedicine and Health Sciences; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje biomedicine i zdravstvo (doktor/doktorica znanosti, područje biomedicine i zdravstvo)
• Type of resource: Text
• Extent: 70 str.
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-05-13 10:52:23