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Context Paltusotine is a once-daily, oral, nonpeptide small-molecule somatostatin receptor type 2 (SST2) agonist in clinical development for treatment of acromegaly. Objective This work aimed to evaluate change in insulin-like growth factor I (IGF-I) levels in patients switched from octreotide long-acting release or lanreotide depot monotherapy to paltusotine. Methods A phase 2, open-label, prospective, multicenter, multinational, nonrandomized, single-arm exploratory study was conducted in which dosage uptitrations were performed in a double-blinded manner. At 26 global sites, patients with acromegaly switched to paltusotine from injected somatostatin receptor ligand (SRL)-based therapy. Patients received 13-week treatment with once-daily oral paltusotine (10-40 mg/d). The primary end point was change from baseline to week 13 in IGF-I for patients who switched from long-acting octreotide or lanreotide depot monotherapy to paltusotine (group 1). All patients underwent a 4-week paltusotine washout at end of treatment period (wk 13-17). IGF-I, growth hormone (GH), patient-reported outcome, and safety data were collected. Results Forty-seven patients enrolled. In group 1 (n = 25), IGF-I and GH showed no significant change between SRL baseline and end of paltusotine treatment at week 13 (median change in IGF-I = −0.03×upper limit of normal [ULN]; P = .6285; GH = −0.05 ng/mL; P = .6285). IGF-I and GH rose significantly in the 4 weeks after withdrawing paltusotine (median change in IGF-I = 0.55×ULN; P < .0001 [median increase 39%]; GH = 0.72 ng/mL; P < .0001 [109.1% increase]). No patients discontinued because of adverse events (AE); no treatment-related serious AEs were reported. Conclusion These results suggest once-daily oral paltusotine was effective in maintaining IGF-I values in patients with acromegaly who switched from injected SRLs. Paltusotine was well tolerated with a safety profile consistent with other SRLs.

Purpose Polyglandular autoimmune syndromes (PAS) are complex, heterogeneous disorders in which various autoimmune diseases can occur, affecting both endocrine and non-endocrine organs. In this meta-analysis, the prevalence of associated autoimmune disorders was investigated in PAS II and III. Methods A comprehensive search in MEDLINE and Embase databases identified 479 studies with the keywords of PAS II and PAS III. 18 records containing a total of 1312 patients fulfilled our inclusion criteria (original studies reporting at least 10 cases and containing the combination of other autoimmune disorders) and were selected for further analysis. A meta-analysis of prevalence was performed using the random-effects model with the calculation of 95% confidence intervals (CI). Results of each meta-analysis were displayed graphically using forest plots. Results Distinction between PAS II and PAS III was made in 842 cases, of which 177 and 665 were PAS II and III (21.1 vs 78.9%), respectively. The prevalence of Hashimoto’s thyroiditis was significantly higher than that of Graves’s disease (39% [95% CI 17–65%] vs. 4% [95% CI 0–10%], respectively; p = 0.001). In PAS II, Addison’s disease (AD) coexisted with AITDs, T1DM or the combination of these conditions in 65, 18 and 10% of cases, respectively. In addition, one other endocrine and five non-endocrine organ-specific autoimmune disorders were reported. In PAS III, two other autoimmune endocrinopathies, six non-endocrine organ-specific, and four systemic autoimmune disorders were found in combination with AITDs. Conclusions AITDs, T1DM and AD are the most common combinations in PAS, thus screening for these conditions seems to be reasonable.

A paragangliomák a szimpatikus vagy paraszimpatikus ganglionokból kiinduló, többségükben jóindulatú daganatok, de rosszindulatú formájuk is ismert. A fej-nyak régióban, a glomus caroticumban, illetve a vegetatív idegrendszer dúcláncának megfelelően a hasüregben, illetve a mellüregben is előfordulhatnak. A 39 éves férfi beteg kivizsgálása extrém magas vérnyomásértékek, éjszakai izzadás és 10 kg-os fogyás miatt kezdődött. A mellkas-CT-vizsgálat a jobb oldali tüdőkapuban óriási térfoglalást írt le, a bronchoszkópos mintavétel sikertelen volt. Jobb oldali thoracotomiából mintavétel történt, reszekcióra a kifejezett adhéziók, illetve a szívérintettség miatt nem volt lehetőség. A szövettani vizsgálat eredménye paraganglioma lett, ezt a laborvizsgálatok is támogatták. Ennek megfelelőn szomatosztatinanalóg-terápiát kezdtünk, majd 131I-MIBG-kezelést alkalmaztunk, jó klinikai eredménnyel. A koronarográfia során észleltük, hogy a jobb coronaria két marginális ággal hozzájárul a mellkasi terime vérellátásához. Megfelelő előkészítést követően, szív- és mellkassebészeti beavatkozással a tumor eltávolíthatónak bizonyult, ennek eredményeként a posztoperatív szakban a beteg vérnyomáscsökkentőit elhagytuk. A kontrollok során tumormaradványra utaló jel nem volt. A vérnyomáskiugrások okának keresésekor merüljön fel bennünk a paraganglioma lehetősége is. Ezen esetekben az invazív beavatkozások, amennyiben nem előzi meg őket gyógyszeres előkészítés, akár fatális kimenetellel járhatnak. Az egyre szélesedő terápiás lehetőségek kihasználásával és az intézetek közötti kooperációval az óriás-paragangliomában szenvedő betegek is tumormentessé tehetők. Orv Hetil. 2022; 163(31): 1243–1249.

In this chapter, differentiated thyroid cancer (DTC) is discussed focusing on the advanced-stage disease with emphasis on pitfalls in the risk classification, diagnostic workup, follow-up, and treatment.

Background The prevalence of hyponatremia is highly variable among lung cancer patients. It is also an important predictive factor, according to numerous studies. However, its prevalence and prognostic significance in subgroups of lung cancer patients, e.g. in small cell and non-small cell lung cancers (SCLC and NSCLC, respectively), have not yet been evaluated in a meta-analysis.Methods We report this systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2009) Statement. We have registered our meta-analysis and review’s protocol to the PROSPERO International Prospective Register of Systematic Reviews, with the following registration number: CRD42020167013. A systematic search was done in the following sources: MEDLINE, Embase, CENTRAL, Web of Science, ClinicalTrials.gov, a WHO Global Health Library. We extracted the effect measure for each outcome as the relative risk (RR) with the related 95% confidence interval (CI). Results We identified a total of 8127 potentially eligible studies and we included 25 studies in our evaluation. The prevalence of hyponatremia in lung cancer patients varied between 3% and 56.1% with an average of 23% without any significant differences between the following subgroups: cancer type (p=0.780), gender (p=0.223), age (p=0.773), ECOG state (p=0.317) and the extent of disease (p=0.999). Hyponatremia was more consistently an independent prognostic factor in NSCLC than in SCLC. The overall survival (OS) was significantly lower in hyponatremic compared to normonatremic patients at 10 months (RR: 0.59, 95% CI, 0.47 to 0.74, pConclusions Low serum sodium levels have a negative impact on mortality at 10 and 20 months, which is more pronounced among NSCLC patients. The correction of hyponatremia has a positive effect on OS rates at 10 months, but this advantage disappears by 20 months.

Abstract: Introduction and aim: The worldwide incidence of differentiated thyroid cancer (DTC) has markedly increased during the last few decades. According to the international guidelines, principles of DTC management are in transformation. The aim of our work was to evaluate patients’ current likelihood of recovery. Method: Data of 380 patients treated between 1/Jan/2005 and 1/May/2016 at the PTE KK Ist Department of Internal Medicine were retrospectively analyzed. Female/male ratio was 306/74. Median age at diagnosis was 46 years (13–86 years), while median follow-up time was 55 months (0–144 months). Response to therapy was evaluable in 337 patients. Statistical analysis was done using SPSS (version 22.0). Results: Based on the prevalence of papillary (PTC) and follicular (FTC) carcinomas (79/21%), moderate iodine deficiency has to be considered in this region. PTC patients were significantly younger and were diagnosed in earlier tumor stage. The ratio of lymph node and distant metastases was 35%/4% in PTC and 15%/14% in FTC. Radioiodine treatment was performed in a total of 542 times. 264 patients with PTC were followed up. 59% of patients were tumor-free, in 20% uncertain response, in 7% incomplete biochemical response, in 14% incomplete structural response were diagnosed and 6 patients died. Patients with FTC (n = 73) were tumor-free in 59%, uncertain response was found in 10%, incomplete structural response was diagnosed in 31%, while 10% of the patients died. Conclusions: In summary, although DTC has a favorable prognosis, in 31% of FTC patients and in 14% of PTC patients, tumor-free status was not achieved. During the median 55-month follow-up period, the disease-specific mortality was 10% in FTC and 2% in PTC. Orv Hetil. 2018; 159(22): 878–887.

Patients with acromegaly not cured by surgery are often initially treated with injected peptide long-acting somatostatin receptor ligands (SRLs). Non-peptide small molecules can also activate the somatostatin receptor and do so with a high degree of precision for the target therapeutic receptor subtype. Paltusotine (formerly {"type":"entrez-protein","attrs":{"text":"CRN00808","term_id":"1048626668","term_text":"CRN00808"}}CRN00808) is a small molecule somatostatin type 2 (SST2) receptor agonist with high oral bioavailability (70%) and pharmacokinetic profile suitable for once daily dosing. In healthy volunteers, paltusotine has been shown to lower growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. We hypothesized that patients with acromegaly could switch from injected SRLs to once daily oral paltusotine while maintaining baseline IGF-1 levels. ACROBAT Edge ({"type":"clinical-trial","attrs":{"text":"NCT03789656","term_id":"NCT03789656"}}NCT03789656) was a single-arm study designed to evaluate the safety and efficacy of switching from injected SRLs to paltusotine in patients with acromegaly. The primary analysis population consisted of those who had not achieved normal IGF-1 levels despite stable therapy with long-acting octreotide or lanreotide. Eligible patients received their last injection of SRL 4 weeks prior to switching to once daily oral paltusotine monotherapy for a 13-week treatment period. The starting dose of 10 mg per day was uptitrated in 10 mg increments at specified study visits to a maximal dose of 40 mg per day based on protocol specified study drug toleration and IGF-1 criteria. The primary endpoint was change in IGF-1 from baseline to the completion of the 13-week treatment period. Statistical testing was based on non-parametric Wilcoxon Sign Rank test of whether the median change is different from zero. In addition, the rise in IGF-1 during a 4-week washout period was used to provide supportive evidence of efficacy. Twenty-five patients were enrolled in the primary analysis group, three patients discontinued from the study for non-study drug related reasons, two during the treatment period and one during the washout period after completing treatment. The primary endpoint was achieved as paltusotine treatment resulted in no significant change in IGF-1 levels at week 13 compared to baseline [change in IGF-1 =-0.034 (-0.107, 0.107), median (IQR), p>0.6]. Of the 23 patients who completed the dosing period, 20 (87%) achieved IGF-1 levels at the end of treatment that were within 20% of baseline or lower. Median IGF-1 values rose significantly after paltusotine washout (p 10%) included: headache, arthralgia, fatigue, peripheral swelling, paresthesia and hyperhidrosis. There were no discontinuations due to adverse events and no treatment related serious adverse events. These results suggest that patients with acromegaly treated with injected SRLs can switch to oral paltusotine while maintaining IGF-1 and that paltusotine appeared to be well tolerated.

The first classic theranostic agent, radioactive iodine was used in the treatment of differentitated thyroid cancer (DTC) and it has an important role in the good prognosis of DTC even nowadays. I-131 provides a specific, molecular targeted therapy through the active uptake of iodide by sodium iodide symporter. The development of other theranostics also aimed the personalized therapy with minimal side effects and optimal therapeutic efficacy. The incidence of DTC which basically has good prognosis is increasing rapidly worldwide. This required the modification of guidelines to avoid the overtreatment of the disease, in the direction of less radical therapy. Currently, new pathological classification and staging systems were reported. The present work summarizes the new recommendations in the management of DTC, focusing on the indications of radioiodine therapy and reviewing the proposal of the Hungarian consensus conference.

BackgroundTransition of adolescents from pediatric to adult care is of great importance in the management of inflammatory bowel disease (IBD). Our aim was to review and summarize the currently applied interventions and outcomes related to transition practices in IBD.MethodsA systematic review was performed in accordance with the PRISMA Statement. We searched PubMed, EMBASE, CENTRAL, and Web of Science databases up to February 15, 2019. Controlled studies evaluating adolescents and young adults with IBD participating in structured transition interventions or patient educational programs and single-arm (before-after) studies were included. Several individual, health care, and social outcomes were assessed. The PROSPERO registration number is CRD42019118520.ResultsA total of 23 articles were eligible for qualitative synthesis. Eleven studies compared an intervention to a control group, whilst 12 studies were uncontrolled before-after studies. The age of the participants varied from 11 to 25 years. The most common structured transition interventions were joint visits and patient education programs. IBD nurses were operating as nominated transition coordinators in the transition process. Quality of life, patient satisfaction, self-efficacy, disease-specific knowledge, adherence rate, and nonattendance rate at outpatient clinic were identified as main health care transition outcomes besides disease-related outcomes. Despite the various study designs and methodological limitations, outcomes improved with the application of structured transition interventions in eleven of the studies.ConclusionThese results facilitate the design of randomized controlled trials along better standards in transitional care in IBD.

Introduction: The diagnostic algorithm of primary aldosteronism is burdened with uncertainties and, recently, it has been suggested that the sensitivity of the aldosterone/renin ratio used as a screening test – based on the suppression aldosterone – is low. Aim: The primary aim was to test the accuracy of aldosterone/renin ratio. Method: In a retrospective analysis of 309 hypertensive patients supine and ambulatory aldosterone levels were independently examined. Results: Aldosterone/renin ratio was elevated in 99 patients of whom 31 exhibited elevated supine aldosterone, as well. In 34 cases supine aldosterone was increased without elevation of the aldosterone/renin ratio. However, only 3 of them had concomitant low renin levels indicating that primary aldosteronism could not be ruled out. Abnormally increased renin was found in 69 patients, but only 59% of them had increased aldosterone level. Conclusion: Sensitivity of aldosterone/renin ratio is high (91%) if used only in justified cases. Orv. Hetil., 2016, 157(21), 830–835.

The worldwide incidence of differentiated thyroid cancer (DTC) has markedly increased during the last few decades. According to the international guidelines, principles of DTC management are in transformation. The aim of our work was to evaluate patients' current likelihood of recovery.Data of 380 patients treated between 1/Jan/2005 and 1/May/2016 at the PTE KK Ist Department of Internal Medicine were retrospectively analyzed. Female/male ratio was 306/74. Median age at diagnosis was 46 years (13-86 years), while median follow-up time was 55 months (0-144 months). Response to therapy was evaluable in 337 patients. Statistical analysis was done using SPSS (version 22.0).Based on the prevalence of papillary (PTC) and follicular (FTC) carcinomas (79/21%), moderate iodine deficiency has to be considered in this region. PTC patients were significantly younger and were diagnosed in earlier tumor stage. The ratio of lymph node and distant metastases was 35%/4% in PTC and 15%/14% in FTC. Radioiodine treatment was performed in a total of 542 times. 264 patients with PTC were followed up. 59% of patients were tumor-free, in 20% uncertain response, in 7% incomplete biochemical response, in 14% incomplete structural response were diagnosed and 6 patients died. Patients with FTC (n = 73) were tumor-free in 59%, uncertain response was found in 10%, incomplete structural response was diagnosed in 31%, while 10% of the patients died.In summary, although DTC has a favorable prognosis, in 31% of FTC patients and in 14% of PTC patients, tumor-free status was not achieved. During the median 55-month follow-up period, the disease-specific mortality was 10% in FTC and 2% in PTC. Orv Hetil. 2018; 159(22): 878-887.Absztrakt: Bevezetés és célkitűzés: Az elmúlt néhány évtizedben a differenciált pajzsmirigyrákot (DTC) világszerte jelentősen növekvő incidencia jellemezte. A betegek kezelésének alapelvei a nemzetközi irányelveknek megfelelően átalakulóban vannak. Munkánk célja a betegek jelenlegi gyógyulási esélyeinek felmérése volt. Módszer: Retrospektíven elemeztük a Pécsi Tudományegyetem I. Belgyógyászati Klinikáján 2005. január 1-je és 2016. május 1-je között kezelt 380, DTC-ben szenvedő beteg adatait. A nő/férfi arány 306/74 volt. A betegek medián életkora a diagnózis idején 46 év (13–86 év), míg a medián követési idő 55 hónap (0–144 hónap) volt. A terápiás válasz 337 beteg esetében volt értékelhető. A statisztikai feldolgozást az SPSS 22.0 verziójában végeztük. Eredmények: A papillaris (PTC) és a follicularis (FTC) carcinomák előfordulási aránya (79/21%) alapján a régió továbbra is mérsékelten jódhiányosnak tekintendő. A PTC-ben szenvedő betegek szignifikánsan fiatalabbak voltak FTC-ben szenvedő társaiknál, és korábbi tumorstádiumban kerültek felismerésre. A diagnózis idején PTC-ben 35%-ban nyirokcsomó-, 4%-ban távoli áttétet találtunk, FTC-ben ez az arány 15% (N1), illetve 14% (M1) volt. Radiojódkezelésre összesen 542 alkalommal került sor. PTC-ben a követett (n = 264) betegek 59%-a volt tumormentes, 20%-ban bizonytalan választ, 7%-ban inkomplett biokémiai választ és 14%-ban inkomplett strukturális választ diagnosztizáltunk, 6 beteg hunyt el. A FTC-ben szenvedő betegek (n = 73) 59%-a volt tumormentes, 10%-ban bizonytalan választ, 31%-ban residualis betegséget találtunk, a betegek 10%-át elveszítettük. Következtetések: Összefoglalva, bár a DTC jó prognózisú betegség, FTC-ben a betegek 31%-a, míg PTC-ben a betegek 14%-a nem volt tumormentessé tehető. A medián 55 hónapos követési idő alatt a betegségspecifikus halálozás FTC-ben 10%, PTC-ben pedig 2% volt. Orv Hetil. 2018; 159(22): 878–887.

Due to the development and increasing effectiveness of novel cancer therapies, the role of local treatments in metastatic diseases have been increasing in the last decades. The aim of the authors was to present the first successful extracranial stereotactic radiosurgical intervention in Hungary. A 58-year-old male patient with gastric adenocarcinoma underwent surgery and adjuvant chemotherapy. Later, surgical removal of suprarenal gland metastases and first line chemotherapy were carried out. Four years after the first surgery a follow up computed tomographic scan revealed bifocal peritoneal metastases caudally from the edge of the liver and the left kidney with diameters of 2 cm in size. Definitive stereotactic body radiosurgery of 12 Gy single dose was performed using cone beam computed tomography image guidance and intensity modulated arc therapy with two pairs of arcs. The total duration of the procedure was only 25 min and early or late side effects were not observed. Follow up computed tomography scans performed 3 and 7 months after the intervention showed complete regression of the metastases. The authors conclude that stereotactic body radiosurgery can be a safe and effective alternative of metastasis surgery in case of slow growing oligo-metastases. Orv. Hetil., 2015, 156(39), 1593–1599.

The discovery of cardiac hormone production significantly changed the evaluation of the function of the heart, which is rather regarded as a determining factor of the electrolyte and hemodynamic homeostasis cooperating with other organ systems instead of a mechanical pump. The most important hormones produced by the heart are the natriuretic peptides that have the primary role of protection against volume overload through natriuretic, diuretic, vasodilator and antiproliferative effects. They are integrative markers of the cardiac, vascular and renal functions and marking cardiorenal distress. Brain natriuretic peptide and the N-terminal pro-hormone (NT-proBNP) became generally accepted markers of heart failure exceeding traditional pathophysiological significance of those. They are useful in the diagnosis, estimation of prognosis and therapy guidance and their therapeutic administration is also available. Although the detection of extraadrenal aldosterone production is an exciting new discovery, intracardial aldosterone production is not significant in human beings. The intracardial thyroid hormone production is regulated by deiodinase activity. The role of elevated T3 concentration was suggested in the development of cardiac hypertrophy, while low T3 is assumed to be important in adaptation to hypoxia. An unexpected, complex relation can be determined between epicardial adipose tissue and coronary artery diseases, cytokine and adipokine production of adipocytes might be a part of the self-enhancing process of atherosclerosis. Orv. Hetil., 2012, 153, 2041–2047.

In the last decades new therapeutic drugs have been developed for the treatment of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) significantly increase the progression free survival (PFS) of patients with NSCLC carrying epidermal growth factor receptor (EGFR) mutations. This type of lung cancer occurs mainly among non-smoking women and Asian origin. However, the new ESMO guideline recommends EGFR mutation analysis in every patient with NSCLC, because in patients with activating EGFR mutation, TKIs should be considered as first line therapy. In our recent work, we analyzed data of patients with EGFR-mutant adenocarcinoma from January 2009. The number of patients investigated was 446, among them 44 cases were positive for EGFR mutation. The ratio of positive cases was 9.86 % that is lower than the average mutation rate in Europe and much lower than that found in Asia. The exon 19 deletion was detected in 61.4 % of the patients, while L858R point mutation in exon 21 was observed in 34.1 % of them. In one subject, both exon 19 and 21 mutations were present simultaneously. A rare mutation located in exon 21 was found in another patient. TKI therapy was conducted in 38 patients. The disease control rate by TKI therapy was 85.7 %; primary resistance was documented in five subjects. Non-smoking patients with EGFR mutant adenocarcinoma had the highest benefit from TKI treatment. Our data support the recommendation that EGFR mutation status should be defined in all cases of locally advanced or metastatic lung adenocarcinoma.

Due to the development and increasing effectiveness of novel cancer therapies, the role of local treatments in metastatic diseases have been increasing in the last decades. The aim of the authors was to present the first successful extracranial stereotactic radiosurgical intervention in Hungary. A 58-year-old male patient with gastric adenocarcinoma underwent surgery and adjuvant chemotherapy. Later, surgical removal of suprarenal gland metastases and first line chemotherapy were carried out. Four years after the first surgery a follow up computed tomographic scan revealed bifocal peritoneal metastases caudally from the edge of the liver and the left kidney with diameters of 2 cm in size. Definitive stereotactic body radiosurgery of 12 Gy single dose was performed using cone beam computed tomography image guidance and intensity modulated arc therapy with two pairs of arcs. The total duration of the procedure was only 25 min and early or late side effects were not observed. Follow up computed tomography scans performed 3 and 7 months after the intervention showed complete regression of the metastases. The authors conclude that stereotactic body radiosurgery can be a safe and effective alternative of metastasis surgery in case of slow growing oligo-metastases.

Context Congenital hypothyroidism (CH) is one of the most common inborn endocrine disorders with genetic background. Despite the well-established newborn CH screening program in Hungary, no systematic examination of the underlying genetic alterations has been performed yet. Objective We aimed to explore thyrotropin receptor (TSHR) mutations in a cohort of Hungarian patients with CH. Patients 85 unrelated patients with permanent primary CH, all diagnosed at newborn screening, were selected. Main outcome measures Coding exons of the TSHR gene were sequenced and evaluated together with the thyroid-specific clinical parameters. Functional features of the novel mutations were experimentally examined, and their comparative molecular models were built. Results In 4 patients (one heterozygous and three compound heterozygous) 7 TSHR mutations were identified. Among these N4321.50D and P4492.39L are novel missense alterations. Importantly, the N4321.50 residue is highly conserved among G protein-coupled receptors (GPCR-s), and its function has not been examined yet in human glycoprotein hormone receptors (GPHR-s). Our results indicate that the N4321.50D mutation disrupts important, architecture-stabilizing intramolecular interactions, and ultimately lead to the complete intracellular retention of the receptor. On the other hand P4492.39 is located in the intracellular part of the receptor which is important in G protein coupling. The P4492.39L mutation results in signaling impairment, with a more profound effect on the Gq/11 pathway. Conclusion TSHR mutations are common among Hungarian patients with CH. The novel genetic alterations revealed important structural role of the N4321.50 and the P4492.39 residues in receptor expression and signaling, respectively.

ObjectiveThe role of cortisol in the prediction of mortality risk in critical illness is controversial in the literature. The aim of this study was to evaluate the prognostic value of cortisol concentrations in a mixed population of critically ill patients in medical emergencies.DesignIn this prospective, observational study, measurement of total (TC) and free cortisol (FC) levels was made in the serum samples of 69 critically ill patients (39 males and 30 females, median age of 74 years) at admission (0 h) and 6, 24, 48, and 96 h after admission.MethodsCortisol levels were determined using HPLC coupled high-resolution ESI-TOF mass spectrometry. The severity of disease was calculated by prognostic scores. Statistical analyses were performed using the SPSS 22.0 software.ResultsThe range of TC varied between 49.9 and 8797.8 nmol/l, FC between 0.4 and 759.9 nmol/l. The levels of FC at 0, 6, 24, and 48 h and TC at 0, 6 h were significantly elevated in non-survivors and correlated with the predicted mortality. The prognostic value of these cortisol levels was comparable with the routinely used mortality scores. In predictive models, FC at 6, 24, and 48 h proved to be an independent determinant of mortality.ConclusionsThe predictive values of FC in the first 2 days after admission and TC within 6 h are comparable with the complex, routinely used mortality scores in evaluating the prognosis of critically ill patients. The cortisol response probably reflects the severity of disease.

Blood cortisol level is routinely analysed in laboratory medicine, but the immunoassays in widespread use have the disadvantage of cross-reactivity with some commonly used steroid drugs. Mass spectrometry has become a method of increasing importance for cortisol estimation. However, current methods do not offer the option of accurate mass identification. Our objective was to develop a mass spectrometry method to analyse salivary, serum total, and serum free cortisol via accurate mass identification. The analysis was performed on a Bruker micrOTOF high-resolution mass spectrometer. Sample preparation involved protein precipitation, serum ultrafiltration, and solid-phase extraction. Limit of quantification was 12.5 nmol L(-1) for total cortisol, 440 pmol L(-1) for serum ultrafiltrate, and 600 pmol L(-1) for saliva. Average intra-assay variation was 4.7%, and inter-assay variation was 6.6%. Mass accuracy was2.5 ppm. Serum total cortisol levels were in the range 35.6-1088 nmol L(-1), and serum free cortisol levels were in the range 0.5-12.4 nmol L(-1). Salivary cortisol levels were in the range 0.7-10.4 nmol L(-1). Mass accuracy was equal to or below 2.5 ppm, resulting in a mass error less than 1 mDa and thus providing high specificity. We did not observe any interference with routinely used steroidal drugs. The method is capable of specific cortisol quantification in different matrices on the basis of accurate mass identification.