Thyroid hormone anomalies during childhood might affect neurological development, school performance and quality of life, as well as daily energy, growth, body mass index and bone development. ...Thyroid dysfunction (hypo- or hyperthyroidism) may occur during childhood cancer treatment, although its prevalence is unknown. The thyroid profile may also change as a form of adaptation during illness, which is called euthyroid sick syndrome (ESS). In children with central hypothyroidism, a decline in FT4 of >20% has been shown to be clinically relevant. We aimed to quantify the percentage, severity and risk factors of a changing thyroid profile in the first three months of childhood cancer treatment.
In 284 children with newly diagnosed cancer, a prospective evaluation of the thyroid profile was performed at diagnosis and three months after starting treatment.
Subclinical hypothyroidism was found in 8.2% and 2.9% of children and subclinical hyperthyroidism in 3.6% and in 0.7% of children at diagnosis and after three months, respectively. ESS was present in 1.5% of children after three months. In 28% of children, FT4 concentration decreased by ≥20%.
Children with cancer are at low risk of developing hypo- or hyperthyroidism in the first three months after starting treatment but may develop a significant decline in FT4 concentrations. Future studies are needed to investigate the clinical consequences thereof.
As current kidney replacement therapies are not efficient enough for end-stage renal disease (ESRD) treatment, a bioartificial kidney (BAK) device, based on conditionally immortalized human proximal ...tubule epithelial cells (ciPTEC), could represent an attractive solution. The active transport activity of such a system was recently demonstrated. In addition, endocrine functions of the cells, such as vitamin D activation, are relevant. The organic anion transporter 1 (OAT-1) overexpressing ciPTEC line presented 1α-hydroxylase (CYP27B1), 24-hydroxylase (CYP24A1) and vitamin D receptor (VDR), responsible for vitamin D activation, degradation and function, respectively. The ability to produce and secrete 1α,25-dihydroxy-vitamin D₃, was shown after incubation with the precursor, 25-hydroxy-vitamin D₃. The beneficial effect of vitamin D on cell function and behavior in uremic conditions was studied in the presence of an anionic uremic toxins mixture. Vitamin D could restore cell viability, and inflammatory and oxidative status, as shown by cell metabolic activity, interleukin-6 (IL-6) levels and reactive oxygen species (ROS) production, respectively. Finally, vitamin D restored transepithelial barrier function, as evidenced by decreased inulin-FITC leakage in biofunctionalized hollow fiber membranes (HFM) carrying ciPTEC-OAT1. In conclusion, the protective effects of vitamin D in uremic conditions and proven ciPTEC-OAT1 endocrine function encourage the use of these cells for BAK application.
Objective
Treatment of congenital adrenal hyperplasia (CAH) patients with glucocorticoids is often challenging since there is a delicate balance between over‐ and undertreatment. Treatment can be ...monitored noninvasively by measuring salivary androstenedione (A4) and 17‐hydroxyprogesterone (17‐OHP). Optimal treatment monitoring requires the establishment of reference values in saliva.
Design
A descriptive study.
Patients
For this study saliva of 255 healthy paediatric and adult volunteers with an age range of 4–75 years old was used.
Measurements
We developed a sensitive liquid chromatography‐tandem mass spectrometry method, assessed salivary A4 and 17‐OHP stability, and measured A4 and 17‐OHP concentrations in saliva collected in the morning, afternoon, and evening.
Results
We quantified A4 and 17‐OHP concentrations in the morning, afternoon, and evening and demonstrated that there is a significant rhythm with the highest levels in the morning and decreasing levels over the day. A4 and 17‐OHP concentrations display an age‐dependent pattern. These steroids remain stable in saliva at ambient temperature for up to 5 days.
Conclusions
Good stability of the steroids in saliva enables saliva collection by the patient at home. Since salivary A4 and 17‐OHP display a diurnal rhythm and age‐dependent pattern, we established reference values for both children and adults at three time points during the day. These reference values support treatment monitoring of children and adults with CAH.
Abstract
Background
A low vitamin D status has been put forward as a potential risk factor for the development of inflammatory bowel disease (IBD). This study investigated the association between ...prediagnostic circulating vitamin D concentrations and dietary intakes of vitamin D, and the risk of Crohn's disease (CD) and ulcerative colitis (UC).
Methods
Among 359,728 participants of the European Prospective Investigation into Cancer and Nutrition cohort, individuals who developed CD or UC after enrollment were identified. Each case was matched with2 controls by center, gender, age, date of recruitment, and follow-up time. At cohort entry, blood samples were collected and dietary vitamin D intakes were obtained from validated food frequency questionnaires. Serum 25-hydroxyvitamin D levels were measured using liquid chromatography-tandem mass spectrometry. Conditional logistic regression was performed to determine the odds of CD and UC.
Results
Seventy-two participants developed CD and 169 participants developed UC after a median follow-up of 4.7 and 4.1 years, respectively. Compared with the lowest quartile, no associations with the 3 higher quartiles of vitamin D concentrations were observed for CD (p trend = 0.34) or UC (p trend = 0.66). Similarly, no associations were detected when serum vitamin D levels were analyzed as a continuous variable. Dietary vitamin D intakes were not associated with CD (p trend = 0.39) or UC (p trend = 0.83).
Conclusions
Vitamin D status was not associated with the development of CD or UC. This does not suggest a major role for vitamin D deficiency in the etiology of IBD, although larger studies are needed to confirm these findings.
Abstract
Objectives
Testosterone testing is relevant for evaluating castration adequacy and diagnosis of castration-resistant prostate cancer (PCa). However, the recommended testosterone cut-off of ...1.7 nmol/L (50 ng/dL) to define adequate castration is based on consensus and not validated for the automated immunoassays (AIA) used in today’s medical laboratories. Furthermore, appropriate population intervals have not been determined by a state-of-the-art assay. We investigated the analytical suitability of this cut-off and the accuracy of the present-day AIAs for testosterone analysis in castrated PCa patients.
Methods
Leftover serum from 120 PCa patients castrated with luteinizing hormone-releasing hormone agonists was analysed for testosterone by five methods: Architect i2000 (Abbott), Access (Beckman), Cobas 6000 (Roche), Atellica (Siemens), LC-MS/MS. For all assays, the castration 95th, 97.5th and 99th percentile upper limits were determined. Furthermore, Passing-Bablok regression, mean bias and Spearman’s correlation coefficients were compared to the LC-MS/MS method and total error based on biological variation.
Results
All castration upper limits, ranging from 0.472 nmol/L (LC-MS/MS) to 1.25 nmol/L (Access) (95% percentile), were significantly lower than the current castration cut-off (1.7 nmol/L). Slopes of Passing-Bablok regressions comparing the AIA with the LC-MS/MS method ranged from 1.4 (Cobas and Atellica) to 3.8 (Access). The Architect showed the highest correlation with LC-MS/MS (ρ=0.58). All AIA failed to meet the desirable total error criterion.
Conclusions
These results suggest that a lower general testosterone castration cut-off may be more appropriate in evaluating the adequacy of castration in PCa and that present-day AIA lack analytical accuracy to quantify testosterone levels in castrated PCa.
The thyroid maintains systemic homeostasis by regulating serum thyroid hormone concentrations. Here we report the establishment of three-dimensional (3D) organoids from adult thyroid tissue ...representing murine and human thyroid follicular cells (TFCs). The TFC organoids (TFCOs) harbor the complete machinery of hormone production as visualized by the presence of colloid in the lumen and by the presence of essential transporters and enzymes in the polarized epithelial cells that surround a central lumen. Both the established murine as human thyroid organoids express canonical thyroid markers PAX8 and NKX2.1, while the thyroid hormone precursor thyroglobulin is expressed at comparable levels to tissue. Single-cell RNA sequencing and transmission electron microscopy confirm that TFCOs phenocopy primary thyroid tissue. Thyroid hormones are readily detectable in conditioned medium of human TFCOs. We show clinically relevant responses (increased proliferation and hormone secretion) of human TFCOs toward a panel of Graves' disease patient sera, demonstrating that organoids can model human autoimmune disease.
This study aimed to investigate whether female BRCA1- and BRCA2 mutation carriers have a reduced ovarian reserve status, based on serum anti-Mullerian hormone (AMH) levels, antral follicle count ...(AFC) and ovarian response to ovarian hyperstimulation. A prospective, multinational cohort study was performed between October 2014 and December 2019. Normo-ovulatory women, aged 18–41 years old, applying for their first PGT-cycle for reason of a BRCA mutation (cases) or other genetic diseases unrelated to ovarian reserve (controls), were asked to participate. All participants underwent a ICSI-PGT cycle with a long-agonist protocol for controlled ovarian hyperstimulation. Linear and logistic regression models were used to compare AMH, AFC and ovarian response in cases and controls. Sensitivity analyses were conducted on BRCA1- and BRCA2 mutation carrier subgroups. Thirty-six BRCA mutation carriers (18 BRCA1- and 18 BRCA2 mutation carriers) and 126 controls, with mean female age 30.4 years, were included in the primary analysis. Unadjusted median AMH serum levels (IQR) were 2.40 (1.80–3.00) ng/ml in BRCA mutation carriers and 2.15 (1.30–3.40) ng/ml in controls (
p
= 0.45), median AFC (IQR) was 15.0 (10.8–20.3) and 14.5 (9.0–20.0),
p
= 0.54, respectively. Low response rate was 22.6% among BRCA mutation carriers and 9.3% among controls,
p
= 0.06. Median number of retrieved oocytes was 9 (6–14) in carriers and 10 (7–13) in controls,
p
= 0.36. No substantial differences were observed between BRCA1- and BRCA2 mutation carriers. Based on several biomarkers, no meaningful differences in ovarian reserve status were observed in female BRCA mutation carriers compared to controls in the context of ICSI-PGT treatment.
•Sample preparation with trichloroacetic acid is frequently used for protein precipitation.•Low concentrations of 2.2% TCA in the prepared sample cause a dip in spray voltage.•The strong acid ...properties of TCA cause current leakage in the spray voltage.•A custom made HESI needle or detaching the union eliminate the leakage current.
Sample clean-up with the protein precipitation solvent trichloroacetic acid (TCA), combined with a stable isotope labeled internal standard, is widely used for the analysis of endogenous and exogenous compounds in serum and plasma with liquid chromatography-tandem mass spectrometry (LC–MS/MS). During the application of an assay for methylmalonic acid (MMA), used for routine analysis in patient care, negative long-term side effects of TCA on assay performance were observed. Step-by-step extensive troubleshooting disclosed the limitations of using TCA in MS. After running over 2000 samples with the MMA assay over a course of one year, a black coating formed between the probe and the heater that was traced to the use of TCA. The MMA assay used a C18 column with an isocratic eluent of 95% water (0.1% formic acid) as starting condition, on which TCA was more retained than MMA. Next, concentrations of 2.2% TCA in the prepared serum or plasma sample caused a drop in spray voltage during ionization into the MS. This was caused by the strong acid properties of TCA, resulting in current loss of the spray voltage between the heated electrospray ionization (HESI) needle and the union holder, which had also a grounding function. Replacing the original metal HESI needle with a custom made fussed silica HESI needle or detaching the union from the union holder, eliminated the effect of the drop in spray voltage. In conclusion, TCA can seriously affect the long-term robustness by affecting the source of the MS. We recommend the use of a very low sample injection volume, and/or shifting the mobile phase to waste when TCA is eluting, when using TCA in LC-MS/MS analysis.
Observational studies suggest that breast-feeding is associated with a more favourable BMI and cardio-metabolic markers, but potential underlying mechanisms are unclear. As serum adiponectin has an ...important function in adults for glucose and lipid metabolism, we assessed 251 participants of the Prevention and Incidence of Asthma and Mite Allergy birth cohort whether breast milk adiponectin is associated with childhood BMI and cardio-metabolic markers. We measured adiponectin levels in breast milk collected around 3 months after birth of the child and subsequently obtained weight and height repeatedly up to the age of 17 years. A medical examination (including blood pressure, glycated Hb and cholesterol) was performed at the age of 8, 12 and 16 years. We used multivariable mixed models to assess the association between breast milk adiponectin and BMI and cardio-metabolic markers at these ages. In models adjusted for exact age of breast milk collection, maternal age, presence of siblings, maternal BMI, pregnancy weight gain and child’s birth weight, each unit increase in log breast milk adiponectin (in ng/ml) was associated with a 0·28 lower BMI z score (95 % CI –0·56, 0·00) at 3 months. After the age of 1 year, there was a tendency towards a higher BMI z score with increased breast milk adiponectin at some ages, but this pattern was not consistent throughout childhood. There were no associations between breast milk adiponectin and any of the cardio-metabolic markers in childhood. We conclude that in our study with follow-up until 17 years of age, breast milk adiponectin has no long-term effect on BMI and cardio-metabolic health during childhood.
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