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Department of Clinical Research, University of Basel, Basel, Switzerland
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Department of Biomedicine, University of Basel, Basel, Switzerland
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Medical Department III, Endocrinology, Nephrology, Rheumatology, University Hospital of Leipzig, Leipzig, Germany
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Department of Clinical Research, University of Basel, Basel, Switzerland
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Osmotic stimulus or stress results in vasopressin release. Animal and human in vitro studies have shown that inflammatory parameters, such as interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α), increase in parallel in the central nervous system and bronchial, corneal or intestinal epithelial cell lines in response to osmotic stimulus. Whether osmotic stimulus directly causes a systemic inflammatory response in humans is unknown. We therefore investigated the influence of osmotic stimulus on circulatory markers of systemic inflammation in healthy volunteers. In this prospective cohort study, 44 healthy volunteers underwent a standardized test protocol with an osmotic stimulus leading into the hyperosmotic/hypernatremic range (serum sodium ≥150 mmol/L) by hypertonic saline infusion. Copeptin – a marker indicating vasopressin activity – serum sodium and osmolality, plasma IL-8 and TNF-α were measured at baseline and directly after osmotic stimulus. Median (range) serum sodium increased from 141 mmol/L (136, 147) to 151 mmol/L (145, 154) (P < 0.01), serum osmolality increased from 295 mmol/L (281, 306) to 315 mmol/L (304, 325) (P < 0.01). Median (range) copeptin increased from 4.3 pg/L (1.1, 21.4) to 28.8 pg/L (19.9, 43.4) (P < 0.01). Median (range) IL-8 levels showed a trend to decrease from 0.79 pg/mL (0.37, 1.6) to 0.7 pg/mL (0.4, 1.9) (P < 0.09) and TNF-α levels decreased from 0.53 pg/mL (0.11, 1.1) to 0.45 pg/mL (0.12, 0.97) (P < 0.036). Contrary to data obtained in vitro, circulating proinflammatory cytokines tend to or decrease in human plasma after osmotic stimulus. In this study, osmotic stimulus does not increase circulating markers of systemic inflammation.
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Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
Department of Burns and Plastic Surgery, The Third Xiangya Hospital, Central South University, Changsha, China
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Objective
Elevated pre-operative C-reactive protein (CRP) serum values have been reported to be associated with poor overall survival for patients with pancreatic neuroendocrine neoplasms (pNEN). The aim of this study was to identify mechanisms linking CRP to poor prognosis in pNEN.
Methods
The malignant properties of pNENs were investigated using the human pNEN cell-lines BON1 and QGP1 exposed to CRP or IL-6. Analyses were performed by ELISA, Western blot, flow cytometry and immunocytochemistry as well as invasion and proliferation assays. To compare cytokine profiles and CRP levels, 76 serum samples of pNEN patients were analyzed using Luminex technology. In parallel, the expression of CRP and growth signaling pathway proteins was assessed on cell lines and paraffin-embedded primary pNEN.
Results
In BON1 and QGP1 cells, inflammation (exposure to IL-6) significantly upregulated CRP expression and secretion as well as migratory properties. CRP stimulation of BON1 cells increased IL-6 secretion and invasion. This was accompanied by activation/phosphorylation of the ERK, AKT and/or STAT3 pathways. Although known CRP receptors – CD16, CD32 and CD64 – were not detected on BON1 cells, CRP uptake of pNEN cells was shown after CRP exposure. In patients, increased pre-operative CRP levels (≥5 mg/L) were associated with significantly higher serum levels of IL-6 and G-CSF, as well as with an increased CRP expression and ERK/AKT/STAT3 phosphorylation in pNEN tissue.
Conclusion
The malignant properties of pNEN cells can be stimulated by CRP and IL-6 promoting ERK/AKT/STAT pathways activation as well as invasion, thus linking systemic inflammation and poor prognosis.
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Objectives
Controversies regarding factors associated with distant metastasis in pediatric thyroid cancer remain among the scientific community. The aim of this study was to investigate factors influencing distant metastasis in pediatric thyroid cancer.
Methods
We reviewed 1376 patients (aged 2 to 18 years) with thyroid cancer treated between 2003 and 2014. Data collected and analyzed included sex, race, age at diagnosis, year of diagnosis, pathological type, number of tumor foci, tumor extension, T-stage, N-stage, surgical procedure and radiation. Univariate and multivariate analyses were conducted to evaluate factors influencing distant metastasis of pediatric thyroid cancer.
Results
In the univariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P < 0.001), N-stage (P < 0.001), number of tumor foci (P = 0.003), tumor extension (P < 0.001) and T-stage (T1 vs T2 (P = 0.803), T3 (P < 0.001) and T4 (P < 0.001)). In multivariate analysis, factors influencing distant metastasis of thyroid cancer were age at diagnosis (P = 0.001), N-stage (P < 0.001) and T-stage (T1 vs T3 (P = 0.036) and T4 (P < 0.001)). Sex, race, year of diagnosis, pathological type, number of tumor foci, tumor extension, surgical procedure and radiation had no significant influence on distant metastasis (all P > 0.05). Furthermore, according to chi-squared test, younger pediatric thyroid cancer patients with higher T- and N-stages are more likely to have distant metastasis.
Conclusion
Age at diagnosis, T-stage and N-stage influence distant metastasis of thyroid cancer patients aged 2 to 18 years; accordingly, more radical treatments may need to be used for patients with those risk elements.
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Introduction
Cancer registry data in the USA indicated that women diagnosed with breast cancer before the age of 40 were at increased risk of a new primary tumour within the brain and women aged 50 years or above were at lower risk than expected. Our aim was to investigate if similar results could be found in Danish population-based data, considering an explanatory role of hormonal status.
Methods
Our study cohort included all women diagnosed with breast cancer below the age of 60 between 1978 and 2013 in Denmark. A total of 47,920 women were followed up in the Danish Cancer Registry for primary brain cancer. Standardized incidence ratios (observed/expected cases (O/E)) were used to estimate the risk of getting a primary brain tumour in the breast cancer cohort.
Results
Data indicated an increased tendency of brain cancer following breast cancer at ages below 60 years (O/E = 1.24). For premenopausal women (age <49 at the diagnosis of breast cancer) the O/E was 1.25. Stratifying by time of breast cancer diagnosis, we observed an increased risk of being diagnosed with a brain tumour among women aged 49 years or younger at breast cancer diagnosis between 2004 and 2013.
Conclusion
The results indicate an increased tendency of developing a primary brain tumour in women with previous breast cancer history. Whereas the finding in premenopausal women is in line with the SEER data, the finding among postmenopausal is not. Primary brain tumours in breast cancer patients call for research in genetics and hormones to establish common risk factors.
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Background
The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown.
Methods
The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley–Pinneau (BP) prediction based on bone age by Greulich–Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated.
Results
The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys.
Conclusions
Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.
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Objective
We aimed to test, whether fetal under- or overnutrition differentially program the thyroid axis with lasting effects on energy metabolism, and if early-life postnatal overnutrition modulates implications of prenatal programming.
Design
Twin-pregnant sheep (n = 36) were either adequately (NORM), under- (LOW; 50% of NORM) or overnourished (HIGH; 150% of energy and 110% of protein requirements) in the last-trimester of gestation. From 3 days-of-age to 6 months-of-age, twin lambs received a conventional (CONV) or an obesogenic, high-carbohydrate high-fat (HCHF) diet. Subgroups were slaughtered at 6-months-of-age. Remaining lambs were fed a low-fat diet until 2½ years-of-age (adulthood).
Methods
Serum hormone levels were determined at 6 months- and 2½ years-of-age. At 2½ years-of-age, feed intake capacity (intake over 4-h following 72-h fasting) was determined, and an intravenous thyroxine tolerance test (iTTT) was performed, including measurements of heart rate, rectal temperature and energy expenditure (EE).
Results
In the iTTT, the LOW and nutritionally mismatched NORM:HCHF and HIGH:CONV sheep increased serum T3, T3:T4 and T3:TSH less than NORM:CONV, whereas TSH was decreased less in HIGH, NORM:HCHF and LOW:HCHF. Early postnatal exposure to the HCHF diet decreased basal adult EE in NORM and HIGH, but not LOW, and increased adult feed intake capacity in NORM and LOW, but not HIGH.
Conclusions: The iTTT revealed a differential programming of central and peripheral HPT axis function in response to late fetal malnutrition and an early postnatal obesogenic diet, with long-term implications for adult HPT axis adaptability and associated consequences for adiposity risk.
Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Department of Pediatrics, China-Japan Friendship Hospital, Beijing, China
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Objectives
We aimed to identify and characterize potential factors, both individually and jointly as a nomogram, associated with short stature and pre-shortness in Chinese preschool-aged children.
Methods
Total of 9501 children aged 3–6 years were recruited from 30 kindergartens in Beijing and Tangshan from September to December 2020 using a stratified random sampling method. Effect-size estimates are expressed as odds ratio (OR) and 95% CI.
Results
The prevalence of short stature and pre-shortness in preschool-aged children was 3.9% (n = 375) and 13.1% (n = 1616), respectively. Factors simultaneously associated with the significant risk for short stature, pre-shortness and both included BMI, paternal height, maternal height, birth weight, birth height, latter birth order (≥2) and less parental patience to children. Besides, breastfeeding duration (≥12 months) was exclusively associated with pre-shortness (OR, 95% CI, P: 1.16, 1.01 to 1.33, 0.037), and childhood obesity with both short stature (3.45, 2.62 to 4.54, <0.001) and short stature/pre-shortness (1.37, 1.15 to 1.64, <0.001). Modeling of significant factors in nomograms had descent prediction accuracies, with the C-index being 77.0, 70.1 and 71.2% for short stature, pre-shortness and both, respectively (all P < 0.001).
Conclusions
Our findings indicate the joint contribution of inherited characteristics, nutrition status from the uterus to childhood, and family psychological environment to short stature and pre-shortness in Chinese preschool-aged children. Further validation in other independent groups is warranted.
Laboratory for Anthropology and Skeletal Biology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
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An increasing number of patients worldwide suffer from bone fractures that occur after low intensity trauma. Such fragility fractures are usually associated with advanced age and osteoporosis but also with long-term immobilization, corticosteroid therapy, diabetes mellitus, and other endocrine disorders. It is important to understand the skeletal origins of increased bone fragility in these conditions for preventive and therapeutic strategies to combat one of the most common health problems of the aged population. This review summarizes current knowledge pertaining to the phenomenon of micropetrosis (osteocyte lacunar mineralization). As an indicator of former osteocyte death, micropetrosis is more common in aged bone and osteoporotic bone. Considering that the number of mineralized osteocyte lacunae per bone area can distinguish healthy, untreated osteoporotic and bisphosphonate-treated osteoporotic patients, it could be regarded as a novel structural marker of impaired bone quality. Further research is needed to clarify the mechanism of lacunar mineralization and to explore whether it could be an additional target for preventing or treating bone fragility related to aging and various endocrine diseases.
Department of Research and Development, Region Kronoberg, Växjö, Sweden
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Department of Endocrinology, Skane University Hospital, Lund, Sweden
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Objective
To explore associations between high midnight salivary cortisol (MSC) secretion and high blood pressure (BP) in type 1 diabetes (T1D).
Methods
Cross-sectional study of 196 adult patients with T1D (54% men). Associations between high MSC (≥9.3 nmol/L) and high systolic BP (>130 mmHg), and high diastolic BP (>80 mmHg) were explored for all patients, users and non-users of antihypertensive drugs (AHD). Adjustments were performed for age, sex, diabetes-related variables, p-creatinine, smoking, physical inactivity, depression and medication.
Results
The prevalence of high MSC differed between patients with high and low systolic BP in all 196 patients: 39 vs 13% (P = 0.001); in 60 users of AHD: 37 vs 12% (P = 0.039), and in 136 non-users of AHD: 43 vs 13% (P = 0.012). Significant associations with high systolic BP were for all patients: physical inactivity (adjusted odds ratio (AOR) 6.5), high MSC (AOR 3.9), abdominal obesity (AOR 3.7), AHD (AOR 2.9), age (per year) (AOR 1.07), and p-creatinine (per µmol/L) (AOR 1.03); for 60 users of AHD: high MSC (AOR 4.1) and age (per year) (AOR 1.11); for 136 non-users of AHD: abdominal obesity (AOR 27.4), physical inactivity (AOR 14.7), male sex (AOR 9.0), smoking (AOR 7.9), and age (per year) (AOR 1.08). High MSC was not associated with high DBP.
Conclusions
In adult patients with T1D, high systolic BP was associated with physical inactivity, high MSC secretion, abdominal obesity, p-creatinine, age, and AHD, the latter indicating treatment failure.
Department of Pediatric Endocrinology and Metabolic Diseases, Mofid Children Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Background
This study was conducted to find out whether boys with constitutional delay in growth and puberty (CDGP) could attain their target height and predicted adult height (PAH) in adulthood or not.
Methods
After measuring the height, weight, pubertal stage, parental height and bone age data of the patients at their first presentation were extracted from the files and their height and weight were measured at the end of the study, wrist X-Ray was performed in order to determine the bone age. PAH was calculated using Bayley–Pinneau method and target height was estimated by mid parental height. Final or near final heights of the patients were measured and compared with the target height and PAH.
Results
The mean age at presentation and the end of study was 15.2 ± 0.95, 20 ± 0.75 years respectively. Mean of bone age at the beginning of study was 12.97 ± 1 years and at the end of study were 17.6 ± 0.58 years. Mean of delayed bone age was 2.2 ± 0.82 years. Mean of the primary measured heights was 150.16 ± 7 cm (138–160 cm). Mean of final or near final heights was 165.7 ± 2.89 cm (161–170.5 cm). Final or near final heights in our subjects were smaller than either their PAH (165.7 ± 2.89 vs 170.7 ± 5.17) (P value <0.005) or target height (165.7 ± 2.89 vs 171.8 ± 4.65) (P value <0.0001).
Conclusion
Most patients with CDGP do not reach their target height or predicted adult height; they are usually shorter than their parents and general population. Such patients need to be followed up until they reach their final height and, in some cases, adjunctive medical treatment might be indicated.
