Analiza testova za preoperativnu dijagnostiku primarnog aldosteronizma

Abstract

Uvod: Primarni aldosteronizam (PA) je prisutan u oko 5% hipertenzivne populacije i povezuje se sa brojnim kardiovaskularnim, renalnim i metaboličkim komplikacijama. Oko trećinu PA čine uni-lateralne forme koje se mogu korigovati hiruški, uglavnom aldosteron produkujući adenom (APA). Za potvrdu dijagnoze PA kod selektovanih hipertenzivnih pacijenata koristi se nekoliko testova od kojih ni jedan nema idealnu pouzdanost. Cilj: Cilj ove studije je bio analiza vrste i validnosti primenjenih testova u preoperativnoj dijagnostici i diferencijalnoj dijagnostici PA i njihova korelacija sa patohistološkim (PH) nalazom i operativnim ishodom. Takođe, analiza kliničko-biohemijskih karakteristika grupe PA upoređenih sa kontrolnim grupama afunkcioni adrenokortikalni tumor sa esencijalnom hipertenzijom (Af tu) i adrenokortikalni tumor sa hiperkortizolizmom (SCS i CS). Metode: Za retrospektivnu analizu korišćeni su podaci iz medicinske dokumentacije koji se odnose na operativno lečenje pacijenata u Centru za endokrinu hirurgiju KCS u periodu od 2007-2017, kao i endokrinološko testiranje u Klinici za endokrinologiju, dijabetes i bolesti metabolizma. Analizirani su dijagnostički testovi za PA, slikovni prikazi adrenalnih tumora, antropometrijski i klinički para-metri, biohemijski, komplikacije (kardiovaskularni događaji, renalna funkcija i morfologija, meta-bolički poremećaji), primenjena operativna tehnika, PH nalaz i postoperativni ishod. Rezultati: U grupi PA (40) operisano je 35 pacijenata, kod 31 je potvrđen adenom, a kod 4 nodularna hiperplazija. U grupi SCS i CS (20) operisano je 19 osoba, a u Af tu (40) tri osobe. U grupi PA je 85% pacijenata imalo bazno povišen serumski aldosteron, a svi hipokalemiju i nisku ili suprimovanu PRA. Od definitivnih testova za potvrdu PA, infuzioni test slanim rastvorom je izveden kod 20, a kaptoprilski test kod 19 ispitanika. Izostanak supresije aldosterona u infuzionom testu nađen je kod svih osoba sa povišenim aldosteronom (najniži postinfuzioni aldosteron 160 ng/L). U kaptoprilskom testu 4 osobe (21%) sa povišenim aldosteronom su imale pad aldosterona za >30%. Najniža postkaptoprilska vrednost aldosterona je bila 135.5 ng/L. Za kriterijum da je PA aldosteron >120 ng/L, sve postkaptoprilske vrednosti su bile obuhvaćene. Primena deksametazon supresionog testa sa 1mg omogućila je potvrdu kosekretornih tumora u dva slučaja (PA i SCS). Adrenalno vensko uzorkovanje aldosterona (AVS) je obavljano sporadično, pa je na osnovu PH nalaza CT pokazao pogrešno da se radi o adenomu u 11.4% slučaja. U grupi PA tumori viđeni CT-om su značajno manji (22.15±9.70), a najveći su u grupi SCS+CS (44.75±14.04). Nađena je pozitivna korelacija težine i volumena tumora sa nivoom kortizola nakon supresije deksametazonom, a negativna korelacija sa nivoom bazalnog aldosterona. Ispitivane grupe se nisu razlikovale prema starosti i polu, ali je za PA (dominantno APA) nađena češća pojava kod mlađih žena (20-40 godina 24:6.7%) i starijih muškaraca (>60 godina 8:60%). Nije bilo značajnih razlika u antropometrijskim karakteristikama među grupama, koje su bile u rangu prekomerne težine. Srednje vrednosti sistolnog, dijastolnog i srednjeg arterijskog pritiska su bile značajno više u grupi PA u odnosu na grupu Af tu, ali ne i grupu SCS+CS. Hipertenzija je značajno duže trajala u grupi PA nego SCS+CS (SV 120 vs 60 m). Nije bilo značajnih razlika u prisustvu pojedinačnih kardiovaskularnih i cerebrovaskularnih događaja. Nisu nađene statistički značajne razlike među grupama za nivo glikemije, zastupljenost intolerancije glukoze i dijabetes melitusa, niti za parametre metabolizma masti. Metabolički sindrom je bio prisutan kod 55% svih ispitanika, najčešći u grupi SCS+CS (70%), zatim Af tu (65%), a najređi u PA (37.5%), značajno ređi u odnosu na druge grupe (p=0,015). Renalne ciste su bile najčešće u grupi PA (30,8%), značajno češće nego u grupi Af tu. Nije bilo značajne razlike među grupama u zastupljenosti renalne insuficijencije, u PA 20%...

is associated with a number of cardiovascular, renal, and metabolic complications. About a third of patients with PA have a unilateral tumour that can be treated surgically. These tumours are usually aldosterone producing adenomas (APA). There are several tests that are used to confirm the diagnosis of PA in patients with hypertension, but none have ideal reliability. Aim: The aim of this study was to analyse the type and validity of applied tests in preoperative diagnosis and differential diagnosis of PA and their correlation with pathohistological (PH) findings and operative outcome. Also, analysis of clinical and biochemical characteristics of the PA group were compared with control groups of patients with afunctional adrenocortical tumours with essential hypertension (Af tu) and patients with adrenocortical tumour and hypercortisolism (SCS and CS). Methods: For the retrospective analysis, data was obtained from medical documentation related to the surgical treatment of patients at the Centre for Endocrine Surgery of the Clinical Centre of Serbia; and from medical documentation related to functional testing performed by endocrinologists at the Clinic for Endocrinology, Diabetes and Metabolic Diseases of the Clinical Centre of Serbia, in the period 2007-2017. The following variables were analysed: diagnostic tests for PA, imaging diagnostics of adrenal tumours, anthropometric, clinical and biochemical parameters, complications (cardiovascular events, renal function and morphology, metabolic disorders), operative technique, definitive PH finding and postoperative outcome. Results: In the PA group of 40 patients, 35 underwent surgery, and an adenoma was confirmed in 31 while nodular hyperplasia was found in four patients. In the group of SCS and CS of 20 patients, 19 underwent surgery while in the Af tu group (40 patients) three underwent surgery. In the PA group, 85% of the patients had baseline elevated serum aldosterone, and all had hypokalaemia and a low or suppressed PRA. Of the definitive tests to confirm PA, the saline infusion test was performed in 20 subjects and the captopril test in 19 subjects. Absence of aldosterone suppression in the infusion test was found in all subjects with elevated aldosterone (lowest post-infusion aldosterone 160 ng/L). In the captopril test, four patients (21%) with elevated aldosterone had a drop in aldosterone greater than 30%. The lowest post-captopril aldosterone value was 135.5 ng/L. In the PA group, for the criteria of aldosterone >120 ng/L all post-captopril values were included. The use of dexamethasone suppression test with 1 mg enabled the confirmation of co-secretory tumours in two cases (PA and SCS). Adrenal venous aldosterone sampling (AVS) was performed sporadically, so based on the PH findings, CT incorrectly showed that it was an adenoma in 11.4% of cases. In the PA group, the tumours seen by CT were significantly smaller (22.15 ± 9.70mm), and the largest were in the SCS + CS group (44.75 ± 14.04mm). A positive correlation was found between tumour weight and volume and cortisol levels after dexamethasone suppression, and a negative correlation was found with basal aldosterone levels.The study groups did not differ by age and sex, but PA (predominantly APA) was more common in younger women (20-40 years 24% vs. 6.7%) and older men (>60 years 8% vs. 60%). There were no significant differences in anthropometric characteristics between the overweight groups. The mean values of systolic, diastolic and mean arterial pressure were significantly higher in the PA group compared to the Af tu group, but not in the SCS + CS group. Hypertension lasted significantly longer in the PA group than SCS + CS (SV 120 vs 60 m). There were no significant differences in the presence of individual cardiovascular and cerebrovascular events. No statistically significant differences were found between the groups for their glycaemic level, prevalence of glucose intolerance and diabetes mellitus, or for any fat metabolism parameters.Metabolic syndrome was present in 55% of all patients, the most common being in the SCS + CS group (70%), followed 7 by Af tu (65%), while the rarest was in the PA group (37.5%), significantly less common than in other groups (p = 0.015). Renal cysts were more common in the PA group (30.8%), significantly more common than in the Af group. There was no significant difference between the groups in the prevalence of renal insufficiency it was 20% in the PA group,but was not significant...