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Free access

Tristan Struja, Hannah Fehlberg, Alexander Kutz, Larissa Guebelin, Christian Degen, Beat Mueller, and Philipp Schuetz

Background

Identification of pretreatment risk factors predicting relapse in patients with hyperthyroidism of Graves’ disease after stopping anti-thyroid drugs (ATD) is decisive to guide therapeutic options.

Purpose

We performed a systematic search and meta-analysis to study predictors for relapse after stopping ATD in patients with Graves’ disease.

Methods

Based on a pre-specified protocol, we searched PubMed, EMBASE and Cochrane in July 2015 for case–control, controlled and randomized-controlled trials reporting risk factors for relapse after stopping ATD. The primary endpoint was relapse of disease until follow-up. PRISMA and SIGN statements were used for reviewing the data and assessing the quality of included trials.

Results

We included 54 trials with a total of 7595 participants. Most trials were small with moderate-to-high risk for bias. Ten trials were assessed only qualitatively (2227 patients), genomic data were reported in 13 trials (2178 patients) and 31 trials (4346 patients) were assessed quantitatively. In total, there were 3696 relapses in 7595 patients (48.7%). By using random-effects meta-analysis, orbitopathy, smoking, thyroid volume measured by sonography, goiter size, fT4, tT3, TRAb and TBII were significantly associated with relapse, whereas male vs female sex, age and initial tT4 level did not show significant associations.

Conclusions

This analysis found several risk factors to predict relapse in Graves’ disease, which can be combined in a risk score. Prospective studies should evaluate the prognostic accuracy of such a score to guide treatment decisions.

Restricted access

Alexander Kutz, Anna Conen, Claudia Gregoriano, Sebastian Haubitz, Daniel Koch, Oliver Domening, Luca Bernasconi, Beat Mueller, and Philipp Schuetz

Objective

While evidence on the interface between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing.

Design and Methods

In this exploratory study, we prospectively included adult patients (aged ≥18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors.

Results

COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs. 66.8pmol/l, -52.7% [95%CI -68.5% to -36.9%]; angiotensin II: 37.7 vs. 92.5pmol/l, -59.2% [95%CI -72.1% to -46.3%]; angiotensin (1-5): 3.3 vs. 6.6pmol/l, -49.7% [95%CI -59.2% to -40.2%]; angiotensin (1-7): 4.8 vs. 7.6pmol/l, -64.9% [95%CI -84.5% to -45.3%]). While the plasma renin activity (PRA-S) was lower in COVID-19 patients (88.6 vs. 207.9pmol/l, -58.5% [95%CI -71.4% to -45.6%]), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors.

Conclusions

As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.

Free access

Tristan Struja, Marina Kaeslin, Fabienne Boesiger, Rebecca Jutzi, Noemi Imahorn, Alexander Kutz, Luca Bernasconi, Esther Mundwiler, Beat Mueller, Mirjam Christ-Crain, Fabian Meienberg, Fahim Ebrahimi, Christoph Henzen, Stefan Fischli, Marius Kraenzlin, Christian Meier, and Philipp Schuetz

Context

First-line treatment in Graves’ disease is often done with antithyroid agents (ATD), but relapse rates remain high making definite treatment necessary. Predictors for relapse risk help guiding initial treatment decisions.

Objective

We aimed to externally validate the prognostic accuracy of the recently proposed Graves’ Recurrent Events After Therapy (GREAT) score to predict relapse risk in Graves’ disease.

Design, setting and participants

We retrospectively analyzed data (2004–2014) of patients with a first episode of Graves’ hyperthyroidism from four Swiss endocrine outpatient clinics.

Main outcome measures

Relapse of hyperthyroidism analyzed by multivariate Cox regression.

Results

Of the 741 included patients, 371 experienced a relapse (50.1%) after a mean follow-up of 25.6 months after ATD start. In univariate regression analysis, higher serum free T4, higher thyrotropin-binding inhibitor immunoglobulin (TBII), younger age and larger goiter were associated with higher relapse risk. We found a strong increase in relapse risk with more points in the GREAT score from 33.8% in patients with GREAT class I (0–1 points), 59.4% in class II (2–3 points) with a hazard ratio of 1.79 (95% CI: 1.42–2.27, P < 0.001) and 73.6% in class III (4–6 points) with a hazard ratio of 2.24 (95% CI: 1.64–3.06, P < 0.001).

Conclusions

Based on this retrospective analysis within a large patient population from a multicenter study, the GREAT score shows good external validity and can be used for assessing the risk for relapse in Graves’ disease, which influence the initial treatment decisions.

Open access

Fahim Ebrahimi, Andrea Widmer, Ulrich Wagner, Beat Mueller, Philipp Schuetz, Mirjam Christ-Crain, and Alexander Kutz

Objective

Adrenal insufficiency in the outpatient setting is associated with excess morbidity, mortality, and impaired quality of life. Evidence on its health-care burden in medical inpatients is scarce. The aim of this study was to assess the health-care burden of primary adrenal insufficiency (PAI) and secondary adrenal insufficiency (SAI) among hospitalized inpatients.

Design and methods

In this nationwide cohort study, adult medical patients with either PAI or SAI hospitalized between 2011 and 2015 were compared with propensity-matched (1:1) medical controls, respectively. The primary outcome was 30-day all-cause in-hospital mortality. Main secondary outcomes included ICU admission rate, length-of-hospital stay, 30-day and 1-year all-cause readmission rates.

Results

In total, 594 hospitalized cases with PAI and 4880 cases with SAI were included. Compared with matched controls, in-hospital mortality was not increased among PAI or SAI patients, respectively. Patients with adrenal insufficiency were more likely to be admitted to ICU (PAI: OR 1.9 (95% CI, 1.27 to 2.72) and SAI: OR 1.5 (95% CI, 1.35 to 1.75)). Length of hospital stay was prolonged by 1.0 days in PAI patients (8.9 vs 7.9 days (95% CI, 0.06 to 1.93)), and by 3.3 days in SAI patients (12.1 vs 8.8 days (95% CI, 2.82 to 3.71)), when compared with matched controls. Patients with SAI were found to have higher 30-day and 1-year readmission rates (14.1 vs 12.1% and 50.0 vs 40.7%; P < 0.001) than matched controls.

Conclusions

While no difference in in-hospital mortality was found, adrenal insufficiency was associated with prolonged length of hospital stay, and substantially higher rates of ICU admission and hospital readmission.