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Context: Osteoporosis and anemia are among the most common diseases in the aging population with an increasing prevalence worldwide., Objective: As the bone-derived hormone fibroblast growth factor 23 (FGF-23) was recently reported to regulate erythropoiesis, we examined age-related associations between hemoglobin levels and bone quality, bone turnover, and FGF-23 concentrations., Design: We used data from more than 5000 adult subjects who participated in the population-based cohorts of the Study of Health in Pomerania (SHIP and SHIP-Trend). Bone quality was assessed by quantitative ultrasound at the heel, bone turnover by measurement of carboxy-terminal telopeptide of type I collagen (CTX), and intact amino-terminal propeptide of type I procollagen (P1NP) serum concentrations, respectively. Anemia was defined as hemoglobin <13 g/dL in men and <12 g/dL in women. Carboxy-terminal FGF-23 levels were measured in plasma in a subset of 852 subjects., Results: Anemic subjects had poorer bone quality, higher fracture risk, and lower serum levels of P1NP than nonanemic individuals. Linear regression models revealed positive associations between hemoglobin and bone quality in subjects aged 40 or above and inverse associations with CTX in subjects aged 60 or above. Hemoglobin and FGF-23 concentrations were inversely associated, while FGF-23 was not related to bone quality or turnover., Conclusion: Our data corroborate a close link between FGF-23 and anemia, which is related to poor bone quality in elderly people. We observed no direct association of FGF-23 with bone parameters. Further studies are needed clarifying the role of FGF-23 on bone and red blood cell production., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Saline infusion testing (SIT) for confirmation of primary aldosteronism (PA) is based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Liquid chromatography tandem mass spectrometry (LC-MS/MS) is increasingly used in clinical routine. We aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the diagnostic utility of steroid panel analysis., Design: Retrospective cohort study of 187 paired SIT samples (2009-2018). Diagnosis of PA (n = 103) and EH (n = 84) was established based on clinical routine workup without using LC-MS/MS values., Setting: Tertiary care center., Methods: LC-MS/MS using a commercial steroid panel. Receiver operator characteristics analysis was used to determine method-specific cut-offs using a positive predictive value (PPV) of 90% as criterion., Results: Aldosterone measured by IA was on average 31 ng/L higher than with LC-MS/MS. The cut-offs for PA confirmation were 54 ng/L for IA (sensitivity: 95%, 95% CI: 89.0-98.4; specificity: 87%, 95% CI: 77.8-93.3; area under the curve (AUC): 0.955, 95% CI: 0.924-0.986; PPV: 90%, 95% CI: 83.7-93.9) and 69 ng/L for LC-MS/MS (79%, 95% CI: 69.5-86.1; 89%, 95% CI: 80.6-95.0; 0.902, 95% CI: 0.857-0.947; 90%, 95% CI: 82.8-94.4). Other steroids did not improve SIT., Conclusions: Aldosterone quantification with LC-MS/MS and IA yields comparable SIT-cut-offs. Lower AUC for LC-MS/MS is likely due to the spectrum of disease in PA and previous decision making based on IA results. Until data of a prospective trial with clinical endpoints are available, the suggested cut-off can be used in clinical routine.

Chemerin is an adipokine associated with parameters of inflammation and the metabolic syndrome. Small observational studies suggested that high circulating chemerin levels are also related to bone erosion. We aimed to determine whether plasma chemerin levels are related to bone quality in the general population and to investigate the influence of body mass index (BMI) on that relation. For our analyses, we obtained data from 3583 adults who participated in the population-based Study of Health in Pomerania-Trend. The participants were divided into three groups according to their BMI: lean (<25 kg/m2), overweight (25 to 30 kg/m2), and obese (≥30 kg/m2). Chemerin concentrations were determined in EDTA plasma. Bone quality was assessed using quantitative ultrasound at the heel. Broadband ultrasound attenuation (BUA), speed of sound (SOS), stiffness index, and osteoporotic fracture risk were derived from this measurement. Sex- and BMI-specific linear regression models revealed inverse associations between chemerin levels and BUA in obese men. In obese women, inverse relations between chemerin levels and SOS or stiffness index were found. Logistic regression models revealed positive associations between chemerin levels and osteoporotic fracture risk. In lean or overweight subjects, no statistically significant associations were found. Our sex- and BMI-specific analyses showed that inverse associations between chemerin levels and bone quality are restricted to obese men and women. The observed association may be due to a chemerin-induced negative affect on bone metabolism, possibly due to abrogation of osteoblastogenesis or stimulation of adipogenesis.

Design: Abnormalities in glucose homeostasis have been described in patients with primary aldosteronism (PA) but most studies show inconsistent results. Therefore, we aimed to compare the prevalence of type 2 diabetes mellitus and metabolic syndrome (MetS) in newly diagnosed PA patients to a matched control cohort of the background population., Methods: In total, 305 PA patients of the prospective German Conn's Registry were compared to the population-based Study of Health In Pomerania (SHIP1; n=2454). A 1:1 match regarding sex, age, and BMI resulted in 269 matched pairs regarding type 2 diabetes and 183 matched pairs regarding MetS. Of the total, 153 PA patients underwent oral glucose tolerance testing (OGTT) at diagnosis and 38 PA patients were reevaluated at follow-up., Results: Type 2 diabetes and MetS were significantly more frequent in PA patients than in the control population (17.2% vs 10.4%, P=0.03; 56.8% vs 44.8%, P=0.02 respectively). Also, HbA1c levels were higher in PA patients than in controls (P<0.01). Of the total, 35.3% of non-diabetic PA patients showed an abnormal OGTT (¼ newly diagnosed type 2 diabetes and ¾ impaired glucose tolerance). PA patients with an abnormal OGTT at baseline presented with significantly improved 2 h OGTT glucose (P=0.01) at follow-up. We detected a negative correlation between 2 h OGTT glucose levels and serum potassium (P<0.01)., Conclusions: Type 2 diabetes and MetS are more prevalent in patients with PA than in controls matched for sex, age, BMI, and blood pressure. This may explain in part the increased cardiovascular disease morbidity and mortality in PA patients., (© 2015 European Society of Endocrinology.)

Context: Activation of the renin-angiotensin-aldosterone system (RAAS) is associated with high serum PTH concentrations and vice versa., Objective: The aim of this study was to analyze the associations of the plasma aldosterone concentration (PAC), the plasma renin concentration (PRC), or the aldosterone to renin ratio (ARR) with serum PTH concentrations in a sample from the general population of northeast Germany., Design: We selected 3105 subjects (25-88 y) from the first 5-year follow-up examination of the Study of Health in Pomerania. The associations of PAC, PRC, or ARR with serum PTH concentrations were examined with multivariable linear regression analyses. We further calculated adjusted mean serum PTH concentrations according to PAC, PRC, and ARR categories (≥90th and < 90th sex specific percentiles and sex specific quartiles). The models were adjusted for age, sex, estimated glomerular filtration rate, serum 25-hydroxy vitamin D concentration, waist circumference, body mass index, hypertension, diabetes mellitus, liver disease, and intake of drugs that affect the RAAS or bone metabolism., Results: We found no associations between PAC or PRC and serum PTH concentrations in fully adjusted linear regression models. However, fully adjusted linear regression and ANOVA models revealed higher serum PTH concentrations in subjects with an ARR 90th percentile or greater than in subjects with a lower ARR., Conclusions: Our data show that a high ARR is associated with high serum PTH concentrations in the general population and thus add to the increasing evidence of a relation between the RAAS and PTH.

Objective: RIA-based sex hormone measurements offer only limited precision and specificity in the low concentration range of women. Therefore, we aimed to establish age-specific reference ranges for serum sex hormone concentrations in women using mass spectrometry and quantile regression., Methods and Results: Data from 985 women aged 20-80 yr, recruited for the prospective Study of Health in Pomerania, were included in the analyses. Quantile regressions models were performed to calculate the age-specific 2.5th and 97.5th percentiles for sex hormone concentrations in women. Serum total testosterone (TT) and androstenedione (AD) concentrations were measured by liquid chromatography-tandem mass spectrometry. Measured concentrations of SHBG and TT were used to calculate free testosterone (free T). TT, AD, and free T concentrations showed a distinct age-related decline across 10-yr age groups (one way ANOVA P < 0.001). Sex hormone reference ranges for TT, AD, and free T were determined across each single year of age and for 10-yr age groups. Reference ranges over the whole age range of 20-80 yr were 0.35-1.97 nmol/liter for TT, 0.89-4.56 nmol/liter for AD, and 0.0025-0.0253 nmol/liter for free T. Separate reference ranges were provided for pre- and postmenopausal women as well as after inclusion of women using oral contraceptives or hormone therapy (n = 1357)., Conclusion: This is the first study to establish age-specific reference ranges for liquid chromatography-tandem mass spectrometry-measured TT and AD and calculated free T concentrations based on quantile regression analyses, accurately accounting for the observed low concentration range and the strong age dependency of these sex hormones in women.

Objective: The aim of this study was to analyze the potential association of the plasma aldosterone concentration (PAC) with the metabolic syndrome (MetS) and its components in two German population-based studies., Methods: We selected 2830 and 2901 participants (31-80 years) from the follow-ups of the Study of Health in Pomerania (SHIP)-1 and the Cooperative Health Research in the Region of Augsburg (KORA) F4 respectively. MetS was defined as the presence of at least three out of the following five criteria: waist circumference ≥94 cm (men (m)) and ≥80 cm (women (w)); high-density lipoprotein (HDL) cholesterol <1.0 mmol/l (m) and <1.3 mmol/l (w); blood pressure ≥130/85 mmHg or antihypertensive treatment; non-fasting glucose (SHIP-1) ≥8 mmol/l, fasting glucose (KORA F4) ≥5.55 mmol/l or antidiabetic treatment; non-fasting triglycerides (SHIP-1) ≥2.3 mmol/l, fasting triglycerides (KORA F4) ≥1.7 mmol/l, or lipid-lowering treatment. We calculated logistic regression models by comparing the highest study- and sex-specific PAC quintiles versus all lower quintiles., Results: MetS was common with 48.1% (m) and 34.8% (w) in SHIP-1 and 42.7% (m) and 27.5% (w) in KORA F4. Our logistic regression models revealed associations of PAC with MetS, elevated triglycerides, and decreased HDL cholesterol in SHIP-1 and KORA F4., Conclusions: Our findings add to the increasing evidence supporting a relation between aldosterone and MetS and suggest that aldosterone may be involved in the pathophysiology of MetS and lipid metabolism disorders.