Stefan Pilz

Background: Previous studies indicated that regional fluctuations in COVID-19 impact were associated with socioeconomic, demographic and environmental factors early in the pandemic. It is unclear whether factors associated with regional COVID-19 mortality and SARS-CoV-2 infections changed over the course of the pandemic. Methods: We evaluated the association of ecological factors with municipality-specific COVID-19 mortality in the national population of Austria between January 2020 and June 2023. Analyses were conducted separately per calendar year and pooled across years via random-effects meta-analysis. Outcomes were analysed using univariable and multivariable zero-inflated negative binomial (ZINB) regression, including annually averaged environmental exposome exposure (including air pollution and UV radiation), socioeconomic, demographic and infection dissemination predictors with significance threshold set to p<0.005. Secondary analysis modelled SARS-CoV-2 infections using of negative-binomial model (NB). Two additional approaches for smaller predictor set selection were applied as sensitivity analyses. Results: Within the entire observation period 18,430 COVID-19 deaths were reported. In univariable analyses (pooled RR (99.5% CI)), COVID-19 mortality was significantly associated with the proportion of commuters (0.79 (0.73-0.86)), residents aged 75-84 (1.18 (1.01-1.37)) and ≥85 years (1.29 (1.04-1.60)), residents with at most compulsory education (1.15 (1.02-1.29)), employed residents aged 15-64 (0.89 (0.85-0.93)), and homeowners (0.91 (0.83-0.99)), as well as with precipitation (0.94 (0.89-0.99)) and the average time with a mean temperature of 5-15 °C (0.95 (0.90-0.99)). In multivariable analyses the share of population aged 85 or older (1.30 (1.09-1.54)) and home ownership (0.92 (0.87-0.98)) were independently significant. Mortality predictor estimates were relatively stable across pandemic years. Across 5,963,882 documented SARS-CoV-2 infections share of employed in 15- to 64-year-olds (1.01 (1.01-1.02)), part-time employment rate (1.01 (1.00-1.02)) and district level nursing care allowance recipiency (0.97 (0.95-0.98)) were associated with detected infections. Overnight stays, population 85 or older, income, compulsory education or less and air pollution all had multiple significant estimates with opposite directionality, leading to non-significant overall associations. Sensitivity analyses outcomes mirrored main analyses outcomes. Conclusions: Throughout the pandemic in Austria, demographic and socioeconomic factors were associated with COVID-19 mortality and infections, but many associations, especially for infections, were unstable over time. These findings underscore the importance of structural vulnerabilities in epidemic impact.

Post-pandemic mortality rates can explore the residual COVID-19 burden and changes in other causes of death. Considering weighted multiple causes of death from death certificates (underlying and others) may help compare post- versus pre-pandemic mortality patterns, while potentially reducing the impact of cause misattribution. Estimates of post-pandemic impact are critical also for proper continuing public health policies (e.g. vaccinations). We retrospectively analyse national all-cause mortality rate ratios between 2024 and pre-pandemic years (2017–2019) for sex-stratified 10-year age groups in Austria. In weighted analyses, the underlying death cause was weighted 50% and other causes shared the remaining 50%. Sensitivity analyses explored different weightings. Cause-specific weightings were also compared between 2024 and 2019. Despite 1212 reported COVID-19 deaths in 2024, all-cause mortality rates were equal or lower in 2024 compared to 2019 in all strata at risk from COVID-19 (i.e., aged 60 years and over). All-cause mortality rates in 2024 were higher than in 2019 in adolescent and young adult strata. The ratio of weighted over unweighted COVID-19 death rates was 0.51–0.58 for age strata 60 years and older and even lower in sensitivity analyses, indicating that COVID-19 deaths were possibly overestimated. Post-pandemic COVID-19 deaths had no visible impact on mortality patterns in Austria and were possibly overcounted. Increased post-pandemic mortality patterns in the young are particularly worrisome.

Importance: Estimates of SARS-CoV-2 vaccine effectiveness (VE) from observational studies may be biased if healthier (healthy vaccinee effect; HVE) or less healthy individuals are preferentially vaccinated. Quantifying HVE is essential for interpreting VE estimates for informed vaccination policy. Objective: To assess the HVE by comparing all-cause mortality, cancer mortality, and deaths from external causes between vaccinated and unvaccinated individuals. Design, Setting, and Participants: This nationwide retrospective cohort study used Austrian national registry data from 2021 to August 31, 2022, and included the entire adult population of Austria with no previously documented SARS-CoV-2 infection on January 1, 2021. Cox regression was used to estimate hazard ratios (HRs) for mortality comparing vaccinated with unvaccinated individuals while adjusting for age, sex and Austrian long-term care allowance (ALTCA) recipiency, stratified by vaccinations (1 to 4). Analyses were performed for the whole observation period, 3-month blocks (quarters) and the 2 months with highest and lowest COVID-19 disease burden per year. Additionally, newly vaccinated individuals were matched on day of vaccination based on the aforementioned covariates plus highest education and HRs were assed for the two weeks following vaccination. Exposure: Receipt of at least 1 dose of SARS-CoV-2 vaccine. Main Outcomes and Measures: All-cause mortality, cancer mortality, and deaths from external causes (e.g., falls and transport accidents). Results: Among 7,416,077 eligible adults, all-cause mortality was lower among vaccinated than unvaccinated individuals regardless of vaccination number. Differences in risk were greatest shortly after vaccination and attenuated over time. E.g., adjusted all-cause HRs in the quarter after vaccination introduction were 0.46, 0.52, 0.38 and 0.43 for vaccinated vs unvaccinated individuals for 1, 2, 3 and 4 vaccinations, respectively. Respective HRs for the first 2 weeks after vaccination in the matched analysis were 0.24-0.32 across all vaccinations. Findings for cancer mortality and deaths from external causes paralleled those for all-cause mortality. Conclusions and Relevance: A pronounced HVE was observed for SARS-CoV-2 vaccination during the pandemic, evidenced by markedly lower mortality from causes not plausibly related to vaccination (cancer, external causes) among vaccinated individuals. This bias needs to be accounted for when interpreting observational estimates of SARS-CoV-2 VE.

Purpose of Review: We summarize and discuss evidence on management of chronic hypoparathyroidism (HypoPT) and primary hyperparathyroidism (PHPT) in pregnancy and lactation to provide guidance for clinical care. Recent Findings: Women with HypoPT are at increased risk of certain pregnancy complications, though most pregnancies are uncomplicated. Conventional therapy with activated vitamin D and calcium is continued throughout pregnancy, but there are unpredictable changes in the required dosages warranting regular surveillance during pregnancy (e.g., all 3 to 4 weeks). Data on parathyroid hormone (PTH) replacement therapy in pregnancy are limited, but a few case reports suggest favourable outcomes with this treatment. During lactation, dosage requirements for conventional therapy of HypoPT are often reduced and usually normalize again after weaning. In women with PHPT, surgical treatment should be pursued before conception. PHPT is not associated with adverse pregnancy outcomes in women with mild hypercalcemia but maternal and fetal complications significantly increase with higher calcium concentrations. There is no clear threshold for this risk increase, but several studies and expert groups support a cut-off concentration of about 2.85 mmol/L in albumin-adjusted calcium and 1.45 mmol/L in ionized calcium. For pregnant women with PHPT and calcium above these cut-off concentrations, parathyroidectomy, preferentially in the second trimester, is recommended. Medical treatment for hypercalcaemic PHPT is limited and requires individual decision making. Immediately after delivery, hypercalcemia may worsen in women with PHPT. Summary: Clinical care of women with HypoPT and PHPT in pregnancy and lactation requires intensive surveillance and consideration of the specific changes in bone and mineral metabolism during these times.

Objective: Increased resting heart rate (RHR) is a typical sign of thyrotoxicosis. RHR may therefore serve as a monitoring tool, but longitudinal data on continuous measures of RHR and thyroid hormones are sparse. We evaluated the association between continuously monitored RHR and thyroid function tests in Graves’ disease (GD). Design: This is a double-center, prospective, longitudinal cohort study in 30 patients with GD on antithyroid drug treatment. Participants were followed up with monthly study visits over six months at two hospitals in Graz, Austria. Methods: Free thyroxine (fT4) and free triiodothyronine (fT3) were measured at each study visit. Participants were encouraged to continuously wear a wristband activity tracker (Fitbit Charge 6) to assess RHR. Associations of RHR (mean value over ten days) with thyroid hormones were determined by generalized estimating equation analyses. Results: From September 2024 to November 2025, we enrolled 30 participants (24 women, mean (SD) age of 40.7 (14.6) years) and performed 176 study visits. Thyrotoxicosis was present in 24 participants (80%) at baseline. One SD increase in RHR of 8.8 beats per minute was associated with fT4 (beta = 0.856, 95% CI: 0.641–1.071, P < 0.001), fT3 (beta = 0.836, 95% CI: 0.620–1.051, P < 0.001), and thyrotoxicosis (odds ratio: 5.134, 95% CI: 2.192–12.025, P < 0.001), respectively. Conclusion: RHR assessed by a wearable device is strongly associated with thyroid hormones in GD. Further trials are required to evaluate whether RHR is useful to guide timing of thyroid function tests during antithyroid drug treatment and for GD diagnostics.

Background/Objectives: An Endocrine Society Clinical Practice Guideline on vitamin D was published in 2024. Its main objective was the use of vitamin D to lower the risk of disease in individuals without established indications for vitamin D treatment or 25-hydroxavitamin D (25(OH)D) testing. The methodology followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the Evidence-to-Decision (EtD) framework. Evidence from randomized controlled trials (RCTs) retrieved by a systematic review was prioritized to inform this guideline. It was concluded that vitamin D supplementation reduces rickets and respiratory tract infections in children, mortality in individuals aged 75 years or older, pregnancy complications (outcomes), and progression of prediabetes to diabetes mellitus. Consequently, empiric vitamin D supplementation was recommended for individuals aged 1 to 18 years and ≥75 years, pregnant women, and individuals with prediabetes. Empiric vitamin D supplementation is defined as a vitamin D intake that exceeds the Dietary Reference Intakes (DRIs) and is implemented without 25(OH)D testing. Methods: This article provides a comprehensive guideline summary and critical appraisal based on a narrative review on scientific publications regarding that guideline. Results: Several publications discussed the 2024 Endocrine Society Clinical Practice Guideline on vitamin D. The main criticisms and discussion relate to unclear vitamin D dosages, guideline applicability to certain populations including controversy with previous vitamin D guidelines, and the implications of 25(OH)D testing. Conclusions: The 2024 Endocrine Society Clinical Practice Guideline on vitamin D followed a rigorous methodological approach with high quality standards but it leaves many open questions and uncertainties warranting clarification.

Zusammenfassung: Die Choosing-Wisely-Initiative wurde im Jahr 2012 gegründet und verfolgt das Ziel, eine Überversorgung in der Medizin zu reduzieren, um so das Allgemeinwohl zu fördern. Die Österreichische Gesellschaft für Endokrinologie und Stoffwechsel (ÖGES) hat in Zusammenarbeit mit dem Institut für Allgemeinmedizin und evidenzbasierte Versorgungsforschung der Medizinischen Universität Graz fünf Choosing-Wisely-Empfehlungen auf dem Gebiet der Endokrinologie veröffentlicht, die in diesem Artikel vorgestellt und diskutiert werden. Diese Empfehlungen lauten wie folgt: 1. „Keine Behandlung mit L‑Thyroxin bei Knoten in der Schilddrüse, außer in ausgewählten Fällen.“ 2. „Zu häufige Knochendichtemessungen vermeiden: Intervalle von weniger als 2 Jahren sind selten notwendig.“ 3. „Keine Testosterontherapie bei älteren Männern außer in Fällen mit nachgewiesenem Hypogonadismus.“ 4. „Kein routinemäßiges Testen auf TPO-Antikörper.“ 5. „Keine routinemäßige Schilddrüsensonographie ohne Anzeichen/Symptome einer Schilddrüsenerkrankung, außer bei Risikopersonen für Schilddrüsenkrebs. Bei Knoten mit geringem Risiko die Indikation/Durchführung von Feinnadelaspirationen einschränken.“ Ressourcen, die in einem Bereich des Gesundheitssystems unnötig verbraucht werden, fehlen in anderen Bereichen, weswegen es eine wichtige ethische Verantwortung ist, zum Wohle der Allgemeinheit eine unnötige Überdiagnostik und Übertherapie zu minimieren.

Zusammenfassung: Im Juli 2025 hat die Endocrine Society eine neue Guideline bezüglich des primären Hyperaldosteronismus (PHA) veröffentlicht, die in diesem Artikel kurz zusammengefasst und diskutiert wird inklusive pragmatischer Hinweise zur Implementierung in die klinische Routine. Es wird in dieser Guideline ein Screening auf einen PHA bei allen (!) Patienten mit arteriellem Hypertonus empfohlen. Die Bestimmung von Aldosteron und Renin sowie der Aldosteron-zu-Renin-Ratio (ARR) ist nach wie vor der empfohlene Screeningtest. Diese Laborbestimmungen können unter jeglicher Medikation, auch ohne Medikamentenumstellungen, erfolgen, wodurch ein breiteres Screening des aktuell massiv unterdiagnostizierten PHA ermöglicht werden soll. Bestätigungstests wie z. B. der Kochsalzbelastungstest sind jedoch kaum mehr notwendig. Bei einem positiven Screeningtest wird das weitere Vorgehen von individuellen Patientencharakteristika abhängig gemacht, wobei in jedem Stadium der Diagnostik die Entscheidung zu einer medikamentösen PHA-Therapie mit vorzugsweise dem Mineralokortikoidrezeptor-Antagonisten (MRA) Spironolacton getroffen werden kann. Neben einer Verbesserung des Blutdrucks und Kaliumspiegels wird nun auch ein Reninanstieg unter MRA-Medikation als Therapieziel definiert. Zusätzlich zur Computertomographie wird zur Subtypenklassifizierung nach wie vor das Nebennierenvenensampling stark propagiert, wobei es auch Evidenz für ein rein CT-Befund-basiertes Vorgehen gibt. Die dichotome Subtypenklassifizierung in einseitige versus beidseitige Aldosteronhypersekretion bzw. operativ versus medikamentös zu therapierenden PHA wird durch histopathologische, genetische und klinische Daten zunehmend in Frage gestellt. Neue medikamentöse Therapieoptionen wie nichtsteroidale MRA und Aldosteronsynthase-Inhibitoren, positive Daten zur erfolgreichen Radiofrequenzablation als Therapiemöglichkeit des PHA und nuklearmedizinische Methoden in der Diagnostik (z. B. ¹¹ C‑Metomidate-PET-CT und ⁶⁸ Ga-Pentixafor-PET-CT), die zumindest so gut wie ein Nebennierenvenensampling sind, eröffnen aktuell auch weitere Möglichkeiten für die Betreuung von Patienten mit PHA.

In the present European Society of Endocrinology (ESE) clinical guideline, we present recommendations for the diagnosis, management, and monitoring of chronic hypoparathyroidism (HypoPT) in adults. Management of HypoPT has changed since the first ESE clinical guideline was published in 2015, as has the knowledge on patient burden of the disease, and the understanding of associated morbidities. In line with the ESE policy, the 2015 guidelines were updated based on up-to-date scientific evidence. As HypoPT is an orphan disease, strong evidence for most outcomes is scarce and recommendations were based on careful synthesis of the literature and expert opinion. Postsurgical HypoPT should be defined as persisting more than 12 months following surgery; recovery could be expected even thereafter (clinical question I [Q I]). For Q II (optimal treatment of chronic HypoPT), relevant data regarding conventional treatment are lacking for clinically relevant endpoints and long-term effects. PTH replacement therapy reduces the pill burden of conventional therapy, improves various biochemical parameters, and potentially improves QoL. We cannot recommend a substantial role for parathyroid allotransplantation in the treatment of chronic HypoPT (Q III). In conclusion, we present recommendations for the diagnosis, management, and monitoring of chronic HypoPT in adults, to give health care providers practical clinical guidance on the management of this condition. The guideline can serve as a source for preparation of educational materials to empower patients and clinicians.