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Universidad La Salle, Posgrado de la Facultad de Ciencias Químicas, Ciudad de México, México
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The incidence of ovarian cancer has been epidemiologically related to female reproductive events and hormone replacement therapy after menopause. This highlights the importance of evaluating the role of sexual steroid hormones in ovarian cancer by the expression of enzymes related to steroid hormone biosynthesis in the tumor cells. This study was aimed to evaluate the presence of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), aromatase and estrogen receptor alpha (ERα) in the tumor cells and their association with the overall survival in 111 patients diagnosed with primary ovarian tumors. Positive immunoreactivity for 17β-HSD1 was observed in 74% of the tumors. In the same samples, aromatase and ERα revealed 66% and 47% positivity, respectively. No association was observed of 17β-HSD1 expression with the histological subtypes and clinical stages of the tumor. The overall survival of patients was improved in 17β-HSD1-positive group in Kaplan–Meier analysis (P = 0.028), and 17β-HSD1 expression had a protective effect from multivariate proportional regression evaluation (HR = 0.44; 95% CI 0.24–0.9; P = 0.040). The improved survival was observed in serous epithelial tumors but not in nonserous ovarian tumors. The expression of 17β-HSD1 in the cells of the serous epithelial ovarian tumors was associated with an improved overall survival, whereas aromatase and ERα were not related to a better survival. The evaluation of hazard risk factors demonstrated that age and clinical stage showed worse prognosis, and 17β-HSD1 expression displayed a protective effect with a better survival outcome in patients of epithelial ovarian tumors.
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Background
Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM.
Methods
A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models.
Results
The PrFT was significantly correlated with β-C-terminal telopeptides of type I collagen (β-CTX) (r = −0.14, P < 0.036), parathyroid hormone (iPTH) (r = −0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = −0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and β-CTX (β = −0.136, P = 0.042) was independent of other variables.
Conclusion
This study showed a negative and independent association between PrFT and β-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.
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Objective
The study aimed to assess the possible systemic effects of intratympanic dexamethasone (IT-Dex) on the hypothalamic–pituitary–adrenal (HPA) axis, inflammation, and bone metabolism.
Design
A prospective cohort study including 30 adult patients of a tertiary referral ENT clinic treated with 9.6 mg IT-Dex over a period of 10 days was carried out.
Methods
Effects on plasma and salivary cortisol concentrations (basal and after low-dose (1 μg) ACTH stimulation), peripheral white blood cell count, and biomarkers for bone turnover were measured before (day 0) and after IT-Dex (day 16). Additional measurements for bone turnover were performed 5 months after therapy. Clinical information and medication with possible dexamethasone interaction were recorded.
Results
IT-Dex was well tolerated, and no effect was detected on the HPA axis (stimulated plasma and salivary cortisol concentration on day 0: 758±184 and 44.5±22.0 nmol/l; day 16: 718±154 and 39.8±12.4 nmol/l; P=0.58 and 0.24 respectively). Concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP) did not differ after dexamethasone (OC on days 0 and 16 respectively: 24.1±10.5 and 23.6±8.8 μg/l; BSAP on day 0, 16, and after 5 months respectively: 11.5±4.2, 10.3±3.4, and 12.6±5.06 μg/l); similarly, there was no difference in the peripheral white blood cell count (5.7×1012/l and 6.1×1012/l on days 0 and 16 respectively).
Conclusions
IT-Dex therapy did not interfere with endogenous cortisol secretion or bone metabolism.
Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
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Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
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Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
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Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
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DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, Germany
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Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
DFG Research Center and Cluster of Excellence for Regenerative Therapies, Technical University, Dresden, Germany
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Center for Healthy Aging, Technische Universität Dresden, Dresden, Germany
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Glucocorticoids (GC) are used for the treatment of inflammatory diseases, including various forms of arthritis. However, their use is limited, amongst others, by adverse effects on bone. The Wnt and bone formation inhibitor sclerostin was recently implicated in the pathogenesis of GC-induced osteoporosis. However, data are ambiguous. The aim of this study was to assess the regulation of sclerostin by GC using several mouse models with high GC levels and two independent cohorts of patients treated with GC. Male 24-week-old C57BL/6 and 18-week-old DBA/1 mice exposed to GC and 12-week-old mice with endogenous hypercortisolism displayed reduced bone formation as indicated by reduced levels of P1NP and increased serum sclerostin levels. The expression of sclerostin in femoral bone tissue and GC-treated bone marrow stromal cells, however, was not consistently altered. In contrast, GC dose- and time-dependently suppressed sclerostin at mRNA and protein levels in human mesenchymal stromal cells, and this effect was GC receptor dependent. In line with the human cell culture data, patients with rheumatoid arthritis (RA, n = 101) and polymyalgia rheumatica (PMR, n = 21) who were exposed to GC had lower serum levels of sclerostin than healthy age- and sex-matched controls (−40%, P < 0.01 and −26.5%, P < 0.001, respectively). In summary, sclerostin appears to be differentially regulated by GC in mice and humans as it is suppressed by GCs in humans but is not consistently altered in mice. Further studies are required to delineate the differences between GC regulation of sclerostin in mice and humans and assess whether sclerostin mediates GC-induced osteoporosis in humans.
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Objective
Parathyroid carcinoma is a rare tumor among parathyroid tumors. Aspiration cytology and needle biopsy are generally not recommended for diagnostic purposes because they cause dissemination. Therefore, it is commonly diagnosed by postoperative histopathological examination. In this study, we investigated whether preoperative inflammatory markers can be used as predictors of cancer in patients with primary hyperparathyroidism.
Design
This was a retrospective study.
Methods
Thirty-six cases of parathyroid carcinoma and 50 cases of parathyroid adenoma (PA) operated with the diagnosis of primary hyperparathyroidism and confirmed histopathologically at Ito Hospital were included in this study. Preoperative clinical characteristics and inflammatory markers (neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio (LMR)) were compared and their values in preoperative prediction were evaluated and analyzed.
Results
Preoperative intact-parathyroid hormone (P = 0.0003), serum calcium (P = 0.0048), and tumor diameter (P = 0.0002) were significantly higher in parathyroid carcinoma than in PA. LMR showed a significant decrease in parathyroid carcinoma (P = 0.0062). In multivariate analysis, LMR and tumor length diameter were independent predictors. In the receiver operating characteristics analysis, the cut-off values for LMR and tumor length diameter were 4.85 and 28.0 mm, respectively, for parathyroid cancer prediction. When the two extracted factors were stratified by the number of factors held, the predictive ability improved as the number of factors increased.
Conclusion
In the preoperative evaluation, a combination of tumor length diameter of more than 28 mm and LMR of less than 4.85 was considered to have a high probability of cancer.
Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Endocrine Unit, Royal Victoria Infirmary, Newcastle upon Tyne, UK
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Background
The highly plastic nature of adrenal cortex suggests the presence of adrenocortical stem cells (ACSC), but the exact in vivo identity of ACSC remains elusive. A few studies have demonstrated the differentiation of adipose or bone marrow-derived mesenchymal stem cells (MSC) into steroid-producing cells. We therefore investigated the isolation of multipotent MSC from human adrenal cortex.
Methods
Human adrenals were obtained as discarded surgical material. Single-cell suspensions from human adrenal cortex (n = 3) were cultured onto either complete growth medium (CM) or MSC growth promotion medium (MGPM) in hypoxic condition. Following ex vivo expansion, their multilineage differentiation capacity was evaluated. Phenotype markers were analysed by immunocytochemistry and flow cytometry for cell-surface antigens associated with bone marrow MSCs and adrenocortical-specific phenotype. Expression of mRNAs for pluripotency markers was assessed by q-PCR.
Results
The formation of colony-forming unit fibroblasts comprising adherent cells with fibroblast-like morphology were observed from the monolayer cell culture, in both CM and MGPM. Cells derived from MGPM revealed differentiation towards osteogenic and adipogenic cell lineages. These cells expressed cell-surface MSC markers (CD44, CD90, CD105 and CD166) but did not express the haematopoietic, lymphocytic or HLA-DR markers. Flow cytometry demonstrated significantly higher expression of GLI1 in cell population harvested from MGPM, which were highly proliferative. They also exhibited increased expression of the pluripotency markers.
Conclusion
Our study demonstrates that human adrenal cortex harbours a mesenchymal stem cell-like population. Understanding the cell biology of adrenal cortex- derived MSCs will inform regenerative medicine approaches in autoimmune Addison’s disease.
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Objective
We aimed to evaluate whether thyroid hormones, autoimmune and thyroid homeostasis status were related to bone turnover in type 2 diabetes.
Methods
The data were obtained from a cross-sectional study, the METAL study. In this study, 4209 participants (2059 men and 2150 postmenopausal women) with type 2 diabetes were enrolled. Thyroid function, thyroid antibodies and three bone turnover markers (BTMs), including a large N-mid fragment of osteocalcin (N-MID osteocalcin), β-C-terminal cross-linked telopeptides of type I collagen (β-CTX) and procollagen type I N-terminal propeptide (P1NP), were measured. Thyroid homeostasis parameters, including the sum activity of step-up deiodinases (SPINA-GD), thyroid secretory capacity (SPINA-GT), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone resistance index (TTSI), were calculated. The associations of thyroid parameters with BTMs were analyzed using linear regression.
Results
Free and total triiodothyronine were positively associated with N-MID osteocalcin and P1NP in both sexes and positively associated with β-CTX in postmenopausal women. Thyroid-stimulating hormone was negatively associated with β-CTX in postmenopausal women, and free thyroxine was negatively associated with N-MID osteocalcin and P1NP in men. SPINA-GD was positively associated with N-MID osteocalcin and P1NP in both sexes. There was a positive relationship of SPINA-GT with β-CTX, a negative relationship of TTSI with β-CTX, and a negative relationship of TSHI with β-CTX and P1NP in postmenopausal women.
Conclusions
Among men and postmenopausal women with type 2 diabetes, significant associations were observed between N-MID osteocalcin, β-CTX and P1NP with thyroid function and thyroid homeostasis. Further prospective studies are warranted to understand the causal relationship and underlying mechanism.
Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan, People’s Republic of China
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Diabetes-induced advanced glycation end products (AGEs) overproduction would result in compromised osseointegration of titanium implant and high rate of implantation failure. 1α,25-dihydroxyvitamin D3 (1,25VD3) plays a vital role in osteogenesis, whereas its effects on the osseointegration and the underlying mechanism are unclear. The purpose of this study was to investigate that 1,25VD3 might promote the defensive ability of osseointegration through suppressing AGEs/RAGE in type 2 diabetes mellitus. In animal study, streptozotocin-induced diabetic rats accepted implant surgery, with or without 1,25VD3 intervention for 12 weeks. After killing, the serum AGEs level, bone microarchitecture and biomechanical index of rats were measured systematically. In vitro study, osteoblasts differentiation capacity was analyzed by alizarin red staining, alkaline phosphatase assay and Western blotting, after treatment with BSA, AGEs, AGEs with RAGE inhibitor and AGEs with 1,25VD3. And the expression of RAGE protein was detected to explore the mechanism. Results showed that 1,25VD3 could reverse the impaired osseointegration and mechanical strength, which possibly resulted from the increased AGEs. Moreover, 1,25VD3 could ameliorate AGEs-induced damage of cell osteogenic differentiation, as well as downregulating the RAGE expression. These data may provide a theoretical basis that 1,25VD3 could work as an adjuvant treatment against poor osseointegration in patients with type 2 diabetes mellitus.
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Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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Department of Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA
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Glucocorticoid use is the most common cause of secondary osteoporosis. Poor skeletal health related to glucocorticoid use is thought to involve inhibition of the Wnt/β-catenin signaling pathway, a key pathway in osteoblastogenesis. Sclerostin, a peptide produced primarily by osteocytes, is an antagonist of the Wnt/β-catenin signaling pathway, raising the possibility that sclerostin is involved in glucocorticoids’ adverse effects on bone. The aim of this study was to determine whether an acute infusion of cosyntropin (i.e. ACTH(1–24)), which increases endogenous cortisol, increases serum sclerostin levels as compared to a placebo infusion. This study was performed using blood samples obtained from a previously published, double-blind, placebo-controlled, randomized, cross-over study among healthy men and women who received infusions of placebo or cosyntropin after being supine and fasted overnight (ClinicalTrials.gov NCT02339506). A total of 17 participants were analyzed. There was a strong correlation (R2 = 0.65, P < 0.0001) between the two baseline sclerostin measurements measured at the start of each visit, and men had a significantly higher average baseline sclerostin compared to women. As anticipated, cosyntropin significantly increased serum cortisol levels, whereas cortisol levels fell during placebo infusion, consistent with the diurnal variation in cortisol. There was no significant effect of cosyntropin as compared to placebo infusions on serum sclerostin over 6–24 h (P = 0.10). In conclusion, this randomized, placebo-controlled study was unable to detect a significant effect of a cosyntropin infusion on serum sclerostin levels in healthy men and women.
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Objective
To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH).
Methods
We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990–2016.
Results
Among the 138 patients, 82 patients (59.4%) were diagnosed with normosmic IHH and 56 patients (40.6%) were diagnosed with Kallmann syndrome (KS). The patients with IHH experienced occasional menses (4.3%), spontaneous thelarche (45.7%) or spontaneous pubarche (50.7%). Women with thelarche had a higher percentage of pubarche (P < 0.001) and higher gonadotropin concentrations (P < 0.01). Olfactory bulb/sulci abnormalities were found during the magnetic resonance imaging (MRI) of all patients with KS. Most patients with IHH had osteopenia and low bone age. Among the 16 women who received gonadotropin-releasing hormone treatment, ovulation induction or assisted reproductive technology, the clinical pregnancy rate was 81.3% and the live birth rate was 68.8%.
Conclusions
The present study revealed that the phenotypic spectrum of women with IHH is broader than typical primary amenorrhoea with no secondary sexual development, including occasional menses, spontaneous thelarche or pubarche. MRI of the olfactory system can facilitate the diagnosis of KS. Pregnancy can be achieved after receiving appropriate treatment.
