Serum levels of bone turnover markers including calculation of Z-scores: Data from a Dutch healthy reference cohort.

Introduction: Bone turnover markers (BTM) are biochemical compounds reflecting different stages of bone metabolism. Their levels change with age and differ between males and females. This makes clinical interpretation and comparison more difficult. Therefore, our aim was to establish BTM reference values which can be used to calculate Z-scores for use in daily clinical practice. Methods: Serum markers of collagen resorption, bone formation/regulation, collagen formation and bone mineralization (sCTX, OC, PINP and BALP, respectively) were measured in non-fasting volunteers without bone-related abnormalities. Raw data was plotted and gender-specific age cohorts were established with their respective means and standard deviations (SD). Z-scores can be calculated using these reference values to correct for the influence of age and gender on BTM. Results: In total, 856 individuals were included of which 486 (57 %) were female. Individuals were aged between 7 and 70 years. Highest serum levels of BTM were found in childhood and puberty. Peak levels are higher in boys than girls and prevail at later ages. In adults, BTM levels decrease before reaching stable nadir levels. In adults, 10-year reference cohorts with means and SD were provided to calculate Z-scores. Conclusion: With our data, Z-scores of sCTX, OC, PINP and BALP can be calculated using reference categories (for age and gender) of Caucasian healthy volunteers. Clinicians can use BTM Z-scores to determine whether there are changes in bone turnover physiology beyond those expected during aging. BTM Z-scores facilitate harmonization of data interpretation in daily clinical practice and research.

Cigarette smoking is associated with higher thyroid hormone and lower TSH levels: the PREVEND study.

PURPOSE: The extent to which smoking is associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) when taking account of clinical variables including alcohol consumption is unclear. We aimed to determine associations of TSH, FT4, and FT3 levels with current smoking. METHODS: A cross-sectional study was performed in 5766 euthyroid participants (Prevention of Renal and Vascular End-Stage Disease cohort). Current smoking was determined by self-report, categorized as never, former, and current (≤20 and >20 cigarettes per day). Smoke exposure was determined by urinary cotinine. RESULTS: Current smoking of ≤20 and >20 cigarettes per day was associated with lower TSH and higher FT3 levels. FT4 levels were higher in subjects smoking <20 cigarettes per day vs. never and former smokers. Current smokers also consumed more alcohol. Multivariable linear regression analyses adjusted for age, sex, anti-TPO autoantibody positivity, alcohol consumption, and other variables demonstrated that lower TSH, higher FT4 and higher FT3 were associated with smoking ≤20 cigarettes per day vs. subjects who never smoked (P < 0.001, P = 0.018, and P < 0.001, respectively) without a further significant incremental effect of smoking >20 cigarettes per day. In agreement, TSH was inversely, whereas FT4 and FT3 levels were positively associated with urinary cotinine (P < 0.001 for each). In contrast, alcohol consumption >30 g per day conferred higher TSH and lower FT3 levels. CONCLUSIONS: Cigarette smoking is associated with modestly higher FT4 and FT3, and lower TSH levels, partly opposing effects of alcohol consumption.

Agreement Between Home-Based Measurement of Stool Calprotectin and ELISA Results for Monitoring Inflammatory Bowel Disease Activity.

BACKGROUND & AIMS: An increasing number of physicians use repeated measurements of stool calprotectin to monitor intestinal inflammation in patients with inflammatory bowel diseases (IBDs). A lateral flow-based rapid test allows patients to measure their own stool calprotectin values at home. The test comes with a software application (IBDoc; Bühlmann Laboratories AG, Schönenbuch, Switzerland) that turns a smartphone camera into a results reader. We compared results from this method with those from the hospital-based reader (Quantum Blue; Bühlmann Laboratories AG) and enzyme-linked immunosorbent assay (ELISA) analysis. METHODS: In a single-center comparison study, we asked 101 participants (10 years of age or older) in the Netherlands to perform the IBDoc measurement on stool samples collected at home, from June 2015 to October 2016. Participants then sent the residual extraction fluid and a fresh specimen from the same bowel movement to our pediatric and adult IBD center at the University Medical Center Groningen, where the level of calprotectin was measured by the Quantum Blue reader and ELISA analysis, respectively. The primary outcome was the agreement of results between IBDoc and the Quantum Blue and ELISA analyses, determined by Bland-Altman plot analysis. RESULTS: We received 152 IBDoc results, 138 samples of residual extraction fluid for Quantum Blue analysis, and 170 fresh stool samples for ELISA analysis. Spearman's rank correlation coefficient was 0.94 for results obtained by IBDoc vs Quantum Blue and 0.85 for results obtained by IBDoc vs ELISA. At the low range of calprotectin level (<500 µg/g), 91% of IBDoc-Quantum Blue results were within the predefined limits of agreement (±100 µg/g), and 71% of IBDoc-ELISA results were in agreement. At the high range of calprotectin level (≥500 µg/g), 81% of IBDoc-Quantum Blue results were within the predefined limits of agreement (±200 µg/g) and 64% of IBDoc-ELISA results were in agreement. CONCLUSIONS: Measurements of fecal levels of calprotectin made with home-based lateral flow method were in agreement with measurements made by Quantum Blue and ELISA, as long as concentrations were <500 µg/g. For patients with concentrations of fecal calprotectin above this level, findings from IBDoc should be confirmed by another method. (Netherlands Trial Registration Number: NTR5133).

No Effect of the Thr92Ala Polymorphism of Deiodinase-2 on Thyroid Hormone Parameters, Health-Related Quality of Life, and Cognitive Functioning in a Large Population-Based Cohort Study.

INTRODUCTION: The presence of the Thr92Ala polymorphism of deiodinase-2 (D2) has been thought to have several effects. It may influence its enzymatic function, is associated with increased expression of genes involved in oxidative stress in brain tissue, and may predict favorable response to combination levothyroxine (LT4) plus triiodothyronine (T3) therapy. It was hypothesized that homozygous carriers of the D2-92Ala allele have different thyroid hormone parameters, and reduced health-related quality of life (HRQoL) and cognitive functioning. METHODS: In 12,625 participants from the LifeLines cohort study with genome-wide genetic data available, the effects of the Thr92Ala polymorphism (rs225014) were evaluated in the general population and in 364 people treated with thyroid hormone replacement therapy, the latter mainly because of primary hypothyroidism. In addition to evaluating anthropometric data, medication use, and existence of metabolic syndrome, HRQoL was assessed with the RAND 36-Item Health Survey, and the Ruff Figural Fluency Test was used as a sensitive test for executive functioning. Data on thyrotropin, free thyroxine (fT4), and free T3 (fT3) levels were available in a subset of 4479 participants. RESULTS: The mean age (±standard deviation) was 53 ± 12 years and the body mass index was 27.0 ± 4.5 kg/m2 in the LT4 users compared with 48 ± 11 years and 26.2 ± 4.1 kg/m2 in participants from the general population. The Ala/Ala genotype of the D2-Thr92Ala polymorphism was present in 11.3% of LT4 users and in 10.7% of the general population. In total, 3742/4479 subjects with thyroid hormone data available had normal TSH (0.4-4.0 mIU/L), and 88% of LT4 users were females. LT4 users had higher fT4, lower fT3, and a lower fT3/fT4 ratio, and female patients had lower scores on the HRQoL domains of physical functioning, vitality, mental health, social functioning, bodily pain, and general health compared with those not using LT4 (p < 0.005). Executive functioning scores, as part of cognitive functioning, were comparable between female LT4 users and the general population. In both groups, the D2-Thr92Ala polymorphism was not associated with differences in TSH, fT4, fT3, the fT3/fT4 ratio, presence of metabolic syndrome or other comorbidities, use of medication, HRQoL, and cognitive functioning. CONCLUSION: The Thr92Ala polymorphism of D2 was not associated with thyroid parameters, HRQoL, and cognitive functioning in the general population and in participants on thyroid hormone replacement therapy.

[Serious sequelae of hypothermia in cryoglobulinaemia]. / Ernstige gevolgen van afkoeling bij cryoglobulinemie.

Cryoglobulinaemia was diagnosed in three patients. The first was a 61-year-old man with severe skin involvement and polyneuropathy caused by type I cryoglobulinaemia associated with a small B cell clone in the bone marrow. A 73-year-old woman presented with neuropathy and renal and skin involvement due to type II cryoglobulinaemia associated with hepatitis C virus infection. The third patient was a 23-year-old woman with skin and renal involvement caused by type III cryoglobulinaemia. Cryoglobulins are circulating proteins that precipitate below a temperature of 37 degrees Celsius. This precipitation causes several signs and symptoms and, in some cases, severe organ damage. According to the Brouet classification, there are three different types of cryoglobulinaemia. Treatment focuses on their underlying causes and on the prevention of cryoglobulin precipitation. It is important to avoid hypothermia, which was the cause of severe manifestations in two of our patients.