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Deutsches Herzzentrum München, Technische Universität München, DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
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Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, Germany
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Germany
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German Centre for Cardiovascular Research (DZHK), Partner Site Munich, Munich, Germany
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Objective
Sex hormone-binding globulin (SHBG) and androgens have been associated with mortality in women and men, but controversy still exists. Our objective was to investigate associations of SHBG and androgens with all-cause and cause-specific mortality in men and women.
Design
1006 men and 709 peri- and postmenopausal women (age range: 45–82 years) from the German population-based KORA F4 cohort study were followed-up for a median of 8.7 years.
Methods
SHBG was measured with an immunoassay, total testosterone (TT) and dihydrotestosterone (DHT) with mass-spectrometry in serum samples and we calculated free testosterone (cFT). To assess associations between SHBG and androgen levels and mortality, we calculated hazard ratios (HRs) with 95% CIs using Cox proportional-hazards models.
Results
In the cohort, 128 men (12.7%) and 70 women (9.9%) died. In women, we observed positive associations of SHBG with all-cause (HR: 1.54, 95% CI: 1.16–2.04) and with other disease-related mortality (HR: 1.86, 95% CI: 1.08–3.20) and for DHT with all-cause mortality (HR: 1.32, 95% CI: 1.00–1.73). In men, we found a positive association of SHBG (HR: 1.24 95% CI: 1.00–1.54) and inverse associations of TT (HR: 0.87, 95% CI: 0.77–0.97) and cFT (HR: 0.84, 95% CI: 0.73–0.97) with all-cause mortality. No other associations were found for cause-specific mortality.
Conclusions
Higher SHBG levels were associated with increased risk of all-cause mortality in men and women. Lower TT and cFT levels in men and higher DHT levels in women were associated with increased risk of all-cause mortality. Future, well-powered population-based studies should further investigate cause-specific mortality risk.
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KORA Study Centre, University Hospital of Augsburg, Augsburg, Augsburg, Germany
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German Centre for Cardiovascular Research (DZHK), Partner site Munich Heart Alliance, Munich, Germany
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German Heart Centre Munich, Technical University of Munich, Munich, Germany
Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
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German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
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Objective
Measurements utilizing commercially available sets of reagents for determination of steroid hormone profiles by liquid chromatography–tandem mass spectrometry (LC-MS/MS) have become increasingly important for routine laboratories. However, method-specific publications of reference intervals obtained from sufficiently large studies are often missing.
Methods
After validation of performance characteristics, a widely available kit for steroid analysis by LC-MS/MS was used to measure concentrations of 15 endogenous steroids (aldosterone, cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, dehydroepiandrosterone sulfate, estradiol, testosterone, androstenedione, dihydrotestosterone, dehydroepiandrosterone, 17-hydroxyprogesterone, 11-deoxycorticosterone, progesterone) in more than 500 blood samples from a population-based study. While randomly selected from a larger cohort, the samples equally represented both sexes and covered a wide range of adult age groups. Age- and sex-specific reference intervals were calculated, and correlation with BMI was assessed.
Results
Performance characteristics of the assay matched expectations for 9 of 15 steroids. For most of them, reference intervals obtained from our study population were comparable to those reported by others, with age and sex being the major determinants. A sex-specific correlation with BMI was found for seven steroids. We identified limitations regarding sensitivity of the method for quantification of progesterone in males and postmenopausal females. Concentrations of aldosterone, 21-deoxycortisol, estradiol, 11-deoxycorticosterone, and dihydrotestosterone could not be quantified in a large percentage of samples.
Conclusions
The reference intervals for nine steroids will support meaningful interpretation for steroid profiles as measured by a widely used kit for LC-MS/MS-based quantification. Laboratories using such kits must be aware of potential limitations in sensitivity for some steroids included in the profile.
Significance Statement
Quantification of steroid hormones is a cornerstone for diagnosis of several diseases. Commonly used immunoassays have limitations in specificity. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) is a promising alternative, particularly if methods are harmonized across laboratories. The use of kits from commercial suppliers might support this. Clinical interpretation of steroid concentrations requires availability of appropriate reference intervals (RIs), but studies on RIs reported in the literature differ in preanalytical and analytical procedures. Here, we provide RIs for steroids measured by a widely available kit under preanalytical conditions mirroring common clinical practice. Such RIs might facilitate interpretation for those using the same method and comparable conditions in clinical routine.
Clinical Cooperation Group Diabetes, LMU München and Helmholtz Zentrum München, Munich, Germany
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Clinical Cooperation Group Diabetes, LMU München and Helmholtz Zentrum München, Munich, Germany
German Center for Diabetes Research (DZD), München-Neuherberg, Germany
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Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany
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Chair of Epidemiology at UNIKAT Augsburg, Ludwig-Maximilians-Universität München, Munich, Germany
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KORA Study Center, University Hospital Augsburg, Augsburg, Germany
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Institute of Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany
DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany
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Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
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Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
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Clinical Cooperation Group Diabetes, LMU München and Helmholtz Zentrum München, Munich, Germany
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Objective
Metabolic syndrome and obesity are risk factors for chronic kidney disease. However, early kidney alterations may escape diagnosis in these conditions due to glomerular hyperfiltration. Uromodulin, a glycoprotein exclusively synthesized in tubular cells of the thick ascending limb of Henle's loop, is a novel tissue-specific biomarker for kidney function. In contrast to the commonly used markers creatinine and cystatin C, serum uromodulin does not primarily depend on glomerular filtration. We hypothesized that serum uromodulin is a marker for metabolic syndrome and related components.
Design
The analyses included 1088 participants of the population-based KORA F4 study aged 62–81 years. Metabolic syndrome was present in 554 participants. After a mean follow-up time of 6.5 years, 621 participants were reevaluated, of which 92 had developed incident metabolic syndrome.
Methods
The association of serum uromodulin with metabolic syndrome and its components were assessed using multivariable logistic regression models.
Results
Serum uromodulin was inversely associated with metabolic syndrome after adjustment for sex, age, estimated glomerular filtration rate, physical activity, smoking, alcohol consumption and high-sensitivity C-reactive protein (OR 0.65; 95% CI 0.56–0.76 per standard deviation uromodulin; P < 0.001). Serum uromodulin was inversely associated with all single components of metabolic syndrome. However, serum uromodulin was not associated with new-onset metabolic syndrome after the follow-up period of 6.5 ± 0.3 years (OR 1.18; 95% CI 0.86–1.60).
Conclusions
Serum uromodulin is independently associated with prevalent, but not with incident metabolic syndrome. Low serum uromodulin may indicate a decreased renal reserve in the metabolic syndrome.
