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Search for other papers by Magdalena Zgliczyńska in
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Objective
Vitamin D plays an important role during pregnancy. The aim was to compare vitamin D status in a group of singleton (SP) and twin pregnancies (TP) using two diagnostic methods: chemiluminescence immunoassay (CLIA) and liquid chromatography with tandem mass spectrometry (LC-MS/MS).
Design
This is a cross-sectional study.
Methods
The study was conducted in the population of SP and TP at the gestational age above 20 + 0 at the Bielanski Hospital in Warsaw, Poland, between October 2020 and January 2023. All patients had their venous blood samples collected and were given an original survey containing questions on demography and vitamin D supplementation.
Results
The study group included 53 Caucasian women with SP and 78 with TP aged from 21 to 47. Considering LC-MS/MS, patients with TP had lower concentrations of 25-hydroxyvitamin D (25(OH)D) than patients with SP. However, no significant difference was observed in the frequency of the occurrence of vitamin D deficiency (25(OH)D < 30 ng/mL). In both groups, the levels obtained with CLIA were significantly lower than in case of LC-MS/MS, however, strongly correlated. The intermethod agreement accounted for 52.4% and the Cohen’s kappa coefficient was 0.142.
Conclusions
The concentration of 25(OH)D in pregnant women depends on the type of gestation (SP/TP) and on the diagnostic methods used (CLIA/LC-MS/MS). Based on LC-MS/MS, the incidence of vitamin D deficiency was low in our group and no differences occurred in its frequency between SP and TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low.
Significance statement
This is the first study to compare the concentration of 25(OH)D levels between SP and TP using two methods: CLIA and the gold standard – LC-MS/MS. Based on LC-MS/MS, a low incidence of vitamin D deficiency was observed in our group, in which the vast majority of patients took cholecalciferol supplements. Moreover, there were no differences in its frequency between SP and TP. However, the 25(OH)D level was significantly lower in TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low, which is associated with substantial clinical implications.
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The link between obesity and low bone strength has become a significant medical concern. The canonical Wnt signaling pathway is a key regulator of mesenchymal stem cell differentiation into either osteoblasts or adipocytes with active Wnt signaling promoting osteoblastogenesis. Our previous research indicated that Dickkopf-1 (Dkk1), a Wnt inhibitor, is upregulated in bone tissue in obesity and that osteoblast-derived Dkk1 drives obesity-induced bone loss. However, Dkk1 is also produced by adipocytes, but the impact of adipogenic Dkk1 on bone remodeling and its role in obesity-induced bone loss remain unclear. Thus, in this study, we investigated the influence of adipogenic Dkk1 on bone homeostasis and obesity-induced bone loss in mice. To that end, deletion of Dkk1 in adipocytes was induced by tamoxifen administration into 8-week-old male Dkk1fl/fl;AdipoQcreERT2 mice. Bone and fat mass were analyzed at 12 and 20 weeks of age. Obesity was induced in 8-week-old male Dkk1fl/fl;AdipoQcre mice with a high-fat diet (HFD) rich in saturated fats for 12 weeks. We observed that 12-week-old male mice without adipogenic Dkk1 had a significant increase in trabecular bone volume in the vertebrae and femoral bones. While histological and serological bone formation markers were not different, the number of osteoclasts and adipocytes was decreased in the vertebral bones of Dkk1fl/fl;AdipoQcre-positive mice. Despite the increased bone mass in 12-week-old male mice, at 20 weeks of age, there was no difference in the bone volume between the controls and Dkk1fl/fl;AdipoQcre-positive mice. Also, Dkk1fl/fl;AdipoQcre-positive mice were not protected from HFD-induced bone loss. Even though mRNA expression levels of Sost, another important Wnt inhibitor, in bone from Dkk1-deficient mice fed with HFD were decreased compared to Dkk1-sufficient mice on an HFD, this did not prevent the HFD-induced suppression of bone formation. In conclusion, adipogenic Dkk1 may play a transient role in bone mass regulation during adolescence, but it does not contribute to bone homeostasis or obesity-induced bone loss later in life.
Search for other papers by Shenghe Luo in
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Department of Cardiology, Yanbian University Hospital, Yanji, China
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To observe the effects of liraglutide (analog of glucagon-like peptide 1 (GLP-1)) on atrial natriuretic peptide (ANP) secretion and atrial dynamics, an ex vivo isolated rat atrial perfusion model was used to determine atrial ANP secretion and pulse pressure. DPP-4−/− mice were also established in vivo. ANP levels were determined by radioimmunoassay; GLP-1 content was determined by Elisa. The expression levels of GLP-1 receptor (GLP-1R), PI3K/AKT/mTOR, piezo 1, and cathepsin K were analyzed by Western blot. In the clinical study, patients with acute coronary syndrome (ACS) had low levels of plasma GLP-1 but relatively high levels of plasma ANP. In ex vivo (3.2 nmol/L) and in vivo (30 μg/kg) models, liraglutide significantly decreased ANP levels and atrial pulse pressure. Exendin9–39 alone (GLP-1R antagonist) reversibly significantly increased ANP secretion, and the reduction effect of liraglutide on the secretion of ANP was significantly alleviated by Exendin9–39. Exendin9–39 demonstrated slightly decreased atrial pulse pressure; however, combined liraglutide and Exendin9–39 significantly decreased atrial pulse pressure. Ly294002 (PI3K/AKT inhibitor) inhibited the increase of ANP secretion by liraglutide for a short time, while Ly294002 didn't counteract the decrease in pulse pressure by liraglutide in atrial dynamics studies. Liraglutide increased the expression of GLP-1R and PI3K/AKT/mTOR in isolated rat atria and the hearts of mice in vivo, whereas Exendin9–39 reversibly reduced the expression of GLP-1R and PI3K/AKT/mTOR. Piezo 1 was significantly decreased in wild type and DPP-4−/− mouse heart or isolated rat atria after being treated with liraglutide. Cathepsin K expression was only decreased in in vivo model hearts. Liraglutide can inhibit ANP secretion while decreasing atrial pulse pressure mediated by GLP-1R. Liraglutide probably plays a role in the reduction of ANP secretion via the PI3K/AKT/mTOR signaling pathway. Piezo 1 and cathepsin K may be involved in the liraglutide mechanism of reduction.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
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Objective
The optimal corticosteroid treatment regimen for subacute thyroiditis has not yet been established. To avoid side effects, tapering of the initial dose of corticosteroid is recommended. With reducing dose, the symptoms can recur.
Design
In a prospective clinical study, a 30-day methylprednisolone (MPSL) treatment protocol with a starting dose of 24 mg/day and tapered by 4 mg every 5 days was assessed for effectiveness and safety regarding possible adrenal insufficiency.
Methods
Fifty-nine patients with subacute thyroiditis were included. At visit 1, after establishing the diagnosis, a short stimulation adrenocorticotrophic hormone (ACTH) test was performed and methylprednisolone treatment was prescribed. At visit 2 (40 ± 5 days after visit 1), clinical, laboratory (including short stimulation ACTH test), and ultrasound evaluation were repeated.
Results
Forty-eight patients (81.4%) were cured by the prescribed protocol, having significantly lower cortisol levels after stimulation at visit 1 than patients who were not cured (mean, 674.9 nmol/L and 764.0 nmol/L, respectively, P = 0.012). Seven patients (12.3%) developed adrenal insufficiency; this group had significantly lower cortisol levels after stimulation at visit 1 than patients without adrenal insufficiency development (mean, 561.5 nmol/L and 704.7 nmol/L, respectively, P = 0.005). Using stimulated cortisol level at visit 1 as the explanatory variable, logistic models were optimized to determine treatment efficacy (AUC = 0.745, optimal threshold 729 nmol/L, specificity 71%, sensitivity 73%) and adrenal function (AUC = 0.861, optimal threshold 629 nmol/L, specificity 73%, sensitivity 100%).
Conclusions
The described protocol was efficient for more than 80% of patients. Using this protocol, the corticosteroid treatment interval is shorter than proposed in current guidelines.
Significance statement
A short but effective protocol for treatment of subacute thyroiditis with methylprednisolone is presented in this article. Using this protocol, the treatment interval is shorter than proposed in current guidelines. Its safety regarding possible adrenal insufficiency is assessed.
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Endometriosis is a chronic, debilitating disease characterized by the growth of endometrial tissues outside the endometrium. Its prevalence seems to differ across ethnicities, with the disease affecting and presenting with advanced stages in Asians more than any other race. Despite this, data on endometriosis in Asians is limited, and there seems to be a lack of support for endometriosis research in Asia. Hence, this review aims to consolidate the available literature on endometriosis in Asians to identify the gaps in knowledge regarding its occurrence in this population and emphasize the need to address the disease in this part of the world. Certain genetic, dietary, and environmental factors that predominate in Asians compared to other ethnicities may potentially impact endometriosis. Understanding these differences is essential in providing innovative strategies for reducing health disparities in endometriosis incidence and presentation across ethnic groups, thus improving disease management and health outcomes.
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Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed growth and delayed pubertal maturation. Hypogonadism may arise from gonadal disease (primary hypogonadism), dysfunction of the hypothalamic–pituitary axis (secondary hypogonadism) or functional hypogonadism. Disrupted puberty (delayed or absent) leading to hypogonadism can have a significant impact on both the physical and psychosocial well-being of adolescents with lasting effects. The diagnosis of hypogonadism in teenagers can be challenging as the most common cause of delayed puberty in both sexes is self-limited, also known as constitutional delay of growth and puberty (CDGP). Although an underlying congenital cause should always be considered in a teenager with hypogonadism, acquired conditions such as obesity, diabetes mellitus, other chronic diseases and medications have all been associated with low sex steroid hormone levels. In this review, we highlight some forms of functional hypogonadism in adolescents and the clinical challenges to differentiate normal variants from pathological states.
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Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have changed considerably the management of type 2 diabetes (T2D). However, recently published data from retrospective cohort studies suggest that chronic exposure to GLP-1RAs in T2D may increase the risk of papillary and medullary thyroid cancer. In this perspective, the role of the incretin system in thyroid carcinogenesis has been reviewed and critically commented on, aiming to understand if the time has arrived to be concerned about the risk. Although evidence suggested, speculative hypotheses should be verified, and further studies are urgently needed to clarify the issue.
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Ruth and Bruce Rappaport School of Medicine, The Technion Institute of Technology, Haifa, Israel
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This study evaluated β-human chorionic gonadotropin (hCG) changes during the early period of pregnancy in an attempt to predict successful pregnancy outcomes in ART. It determined the median values of the β-hCG and the 2-day β-hCG increments of clinical vs biochemical pregnancies. The results of fresh day 3 embryo, frozen day 3 embryo, and frozen day 5 embryo transfers were evaluated. The cutoff values of β-hCG and the 2-day increments predicting clinical pregnancy and delivery were determined. All women who underwent embryo transfer and had a singleton pregnancy from January 2017 to December 2019 were included. As expected, clinical pregnancies had higher initial median β-hCG values compared to biochemical pregnancies (fresh day 3 (400 vs 73 mIU/mL), frozen day 3 (600 vs 268.5 mIU/mL) and frozen day 5 (937 vs 317 mIU/mL)). Nonetheless, the abortion rate was significantly lower in the group with β-hCG above the cutoff values in fresh (141 mIU/mL) and frozen (354.5 mIU/mL) cleavage stage transfers (17.2% vs 44%, P < 0.001 and 18.5% vs 38%, P = 0.003, respectively). Blastocyst transfers resulted in higher median initial β-hCG compared to cleavage embryo transfers (937 vs 600 mIU/mL), and the initial β-hCG values from frozen cleavage embryos were higher compared to fresh cleavage embryos (600 vs 400 mIU/mL). Earlier implantation in frozen cycles may be caused by freezing–thawing procedures. Moreover, in fresh cycles, negative effects of the hormonal milieu of fresh cycles may delay implantation. These results indicate that high initial β-hCG and high 2-day β-hCG increments demonstrated better outcomes, including more clinical pregnancies and fewer abortions.
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Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom
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With increasing evidence of emotional well-being disorders associated with polycystic ovary syndrome (PCOS), effective screening processes are of utmost importance. We studied the impact of using questionnaires to screen for emotional and psychosexual well-being across different models of care for PCOS. We analysed the data from the surveys to assess the difference in the prevalence of emotional and psychosexual ill-being across ethnicity and region. In this prospective cohort study, we invited all women attending consultations for PCOS in Birmingham, UK, and Bengaluru and Navi Mumbai, India. Those who consented to participate in the study were invited to complete a pre-clinic survey about socio-demographic data, Hospital Anxiety and Depression Scale (HADS), Body Image Concern Inventory (BICI), Beliefs about Obese Person scale (BAOP), and Female Sexual Function Index score (FSFI) and a post-clinic survey on clinic experience, lifestyle advice, and specialist referral. A total of 115 women were included in this study. The rate of questionnaire completion was 98.3% (113/115), 97.4% (112/115), 93.04% (107/115), and 84.3% (97/115) for HADS, BICI, BAOP, and FSFI, respectively. In the post-clinic survey, 28.8% reported they were screened for anxiety, 27.1% for depression, and 45.8% for body image concerns. The prevalence of anxiety, depression, and body dysmorphic disorder through pre-clinic survey was 56.5% (50.0% UK vs 59.5% India, P = 0.483), 16.5% (13.9% UK vs 17.7% India, P = 0.529), and 29.6% (36.1% UK vs 26.6% India, P = 0.208), respectively. Surveys with validated questionnaires can improve screening for emotional and psychosexual well-being associated with PCOS which may be missed by ad hoc screening during consultations.
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Background
Fulvestrant resembles estradiol in its structure. Reports have been published concerning fulvestrant measured as estradiol by the immunoassays. This may induce falsely elevated estradiol results and wrongly impact medical decisions. Our aim was to confirm the interference of fulvestrant on estradiol concentration and test a method to identify the false results.
Methods
Four serum samples with low estradiol levels were spiked with fulvestrant at various concentrations. Estradiol was then measured directly on serum (Dir), after a 1:5 dilution (Dil), and a ratio Dil/Dir was estimated. On the second part of the study, estradiol results (Dir, Dil and ratio Dil/Dir) from 14 women treated with fulvestrant were analysed, as well as from 14 patients not under this treatment.
Results
The addition of exogenous fulvestrant to the serum samples induced a gradual rise on estradiol concentration with a mean ratio for the Dil/Dir samples of 2.1 ± 0.4 (range 1.7–2.9). Patients on fulvestrant treatment experienced a mean ratio for the Dil/Dir estradiol sample of 2.4 ± 0.4 (range 1.6–3.0). In the control group, a mean estradiol ratio Dil/Dir of 1.1 ± 0.1 was observed (range 0.8–1.3). No correlation between the number of days after fulvestrant injection and estradiol result (r = 0.531) was observed.
Conclusion
Our study confirmed the interference of fulvestrant in the estradiol measurement by immunoassay. When fulvestrant was present, the estradiol ratio for Dil/Dir sample was about 2. In the control group, the ratio was around 1. The estradiol Dil/Dir ratio is a simple tool which can be used to identify fulvestrant false immunoassay estradiol results.
