Endocrine Research[JOURNAL]
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200 papers
Diagnostic evaluation in steroid-induced myopathy: case report suggesting clinical utility of quantitative muscle ultrasonography.
Minetto MA, Caresio C, D'Angelo V … +5 more , Lanfranco F, Ghizzoni L, Roatta S, Arvat E, Kesari S
Endocr Res · 2018 Nov · PMID 29648902 · Publisher ↗
PURPOSE: We present a patient with adrenal Cushing's syndrome causing steroid myopathy. The purpose of the case report is to illustrate the clinical usefulness of quantitative muscle ultrasonography for the assessment of...
PURPOSE: We present a patient with adrenal Cushing's syndrome causing steroid myopathy. The purpose of the case report is to illustrate the clinical usefulness of quantitative muscle ultrasonography for the assessment of glucocorticoid-induced changes in muscle mass (MM) and structure. METHODS: Assessments of physical performance, muscle strength, MM (i.e., total body skeletal MM, appendicular skeletal MM, and thickness of lower limb muscles), and muscle structure (i.e., echo intensity of lower limb muscles) were performed in the patient both in the active phase of the disease (preoperatively) and 6 months after surgical intervention (postoperatively). RESULTS: Muscle strength, physical performance, and MM were low both preoperatively and postoperatively. We also found preoperatively an increased echo intensity that normalized postoperatively. CONCLUSIONS: Clinical implications of these findings are double-fold. First, although the muscle structure can recover quickly in steroid myopathy patients, the recovery of MM may take months to years. Second, we show that muscle echo intensity can be useful to track the progression of steroid myopathy overtime and may help to indicate early response to therapeutic interventions. Further prospective studies are needed to confirm the value of muscle echo intensity in patients with endogenous or exogenous Cushing's syndrome presenting with steroid myopathy.
Suppressive effects of metformin on T-helper 1-related chemokines expression in the human monocytic leukemia cell line THP-1.
Chen YC, Kuo CH, Tsai YM … +6 more , Lin YC, Hsiao HP, Chen BH, Chen YT, Wang SL, Hung CH
Endocr Res · 2018 Nov · PMID 29630425 · Publisher ↗
PURPOSE OF THE STUDY: Type 1 and type 2 diabetes mellitus (DM) are chronic T-cell-mediated inflammatory diseases. Metformin is a widely used drug for type 2 DM that reduces the need for insulin in type 1 DM. However, whe...
PURPOSE OF THE STUDY: Type 1 and type 2 diabetes mellitus (DM) are chronic T-cell-mediated inflammatory diseases. Metformin is a widely used drug for type 2 DM that reduces the need for insulin in type 1 DM. However, whether metformin has an anti-inflammatory effect for treating DM is unknown. We investigated the anti-inflammatory mechanism of metformin in the human monocytic leukemia cell line THP-1. MATERIALS AND METHODS: The human monocytic leukemia cell line THP-1 was pretreated with metformin and stimulated with lipopolysaccharide (LPS). The production of T-helper (Th)-1-related chemokines including interferon-γ-induced protein-10 (IP-10) and monocyte chemoattractant protein-1 (MCP-1), Th2-related chemokine macrophage-derived chemokine, and the proinflammatory chemokine tumor necrosis factor-α was measured using enzyme-linked immunosorbent assay. Intracellular signaling pathways were investigated using Western blot analysis and chromatin immunoprecipitation assay. RESULTS: Metformin suppressed LPS-induced IP-10 and MCP-1 production as well as LPS-induced phosphorylation of c-Jun N-terminal kinase (JNK), p38, extracellular signal-regulated kinase (ERK), and nuclear factor-kappa B (NF-κB). Moreover, metformin suppressed LPS-induced acetylation of histones H3 and H4 at the IP-10 promoter. CONCLUSIONS: Metformin suppressed the production of Th1-related chemokines IP-10 and MCP-1 in THP-1 cells. Suppressive effects of metformin on IP-10 production might be attributed at least partially to the JNK, p38, ERK, and NF-κB pathways as well as to epigenetic regulation through the acetylation of histones H3 and H4. These results indicated the therapeutic anti-inflammatory potential of metformin.
Effects of intracerebroventricularly injected glucagon-like peptide-2 on ethanol-induced gastric mucosal damage in rats.
Isbil-Buyukcoskun N, Cam B, Gulec Suyen G … +1 more , Ozluk K
Endocr Res · 2018 Nov · PMID 29630414 · Publisher ↗
PURPOSE: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in...
PURPOSE: The present study aims to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-2 (GLP-2) on ethanol-induced gastric mucosal damage and to reveal the mechanisms involved in this effect. MATERIALS AND METHODS: Rats received absolute ethanol orally via an orogastric tube 30 minutes after GLP-2 (1-200 ng/10 µl; i.c.v.) or saline (10 µl) injections. They were decapitated 1 hour later, their stomachs were removed, and the gastric mucosal damage was scored. RESULTS: A total of 100 ng GLP-2 inhibited the gastric mucosal damage by 67%. This effect was abolished by the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) (10 µg/kg; s.c.), but was not affected by either the nitric oxide (NO) synthase inhibitor L-NAME (30 mg/kg; s.c.) or the cyclooxygenase inhibitor indomethacin (5 mg/kg; i.p.). The most effective gastroprotective dose of GLP-2 (100 ng/10 µl; i.c.v.), but not the higher doses (150 or 200 ng/10 µl; i.c.v.) prevented the decrease in gastric mucosal blood flow caused by ethanol. In conclusion, i.c.v. GLP-2 protects against ethanol-induced gastric mucosal damage and this effect is mediated by CGRP receptor activation and gastric mucosal blood flow, but not by NO or prostaglandins.
Excess visceral adiposity is associated with diabetic retinopathy in a multiethnic Asian cohort with longstanding type 2 diabetes.
Moh A, Neelam K, Zhang X … +6 more , Sum CF, Tavintharan S, Ang K, Lee SBM, Tang WE, Lim SC
Endocr Res · 2018 Aug · PMID 29624091 · Publisher ↗
UNLABELLED: Purpose/Aim: Diabetic retinopathy (DR) is the most common diabetic microvascular complication, and it typically develops after 10 years of diabetes diagnosis. The primary aim of this study was to evaluate the...
UNLABELLED: Purpose/Aim: Diabetic retinopathy (DR) is the most common diabetic microvascular complication, and it typically develops after 10 years of diabetes diagnosis. The primary aim of this study was to evaluate the association between adiposity and DR susceptibility among individuals with longstanding type 2 diabetes mellitus (T2D). MATERIALS AND METHODS: In this cross-sectional study, DR was assessed by fundus photography in 953 T2D subjects. DR prevalence by categories of T2D duration was evaluated. In a sub-cohort analysis, subjects having T2D for ≥10 years were divided into DR (N = 241) and non-DR (N = 377) groups. Measures of adiposity including body mass index (BMI), waist circumference (WC), and visceral fat area (VFA) were analyzed. Urinary albumin:creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. RESULTS: DR prevalence markedly increased 10 years after T2D diagnosis (p < 0.001). Among subjects with T2D duration ≥10 years, BMI, WC, and VFA were elevated in DR compared with non-DR (all p < 0.05). Contrasting with BMI and WC, the association between VFA and DR sustained adjustment for demographics, metabolic factors, and insulin treatment (OR: 1.060, 95% CI: 1.004-1.119, p = 0.035). However, the association became insignificant after controlling for ACR and eGFR. Mediation analysis revealed that ACR and eGFR explained 47.3% of the relationship between VFA and DR. CONCLUSIONS: The findings suggest that visceral adiposity is associated with DR in individuals with longstanding T2D. This relationship may be attributable to generalized vascular injury as reflected by coexisting renal burden. Therefore, effective management of visceral adiposity and ameliorating renal burden may ameliorate susceptibility to DR.
Activation of tumor cell integrin αvβ3 by radiation and reversal of activation by chemically modified tetraiodothyroacetic acid (tetrac).
Leith JT, Hercbergs A, Kenney S … +2 more , Mousa SA, Davis PJ
Endocr Res · 2018 Nov · PMID 29611723 · Publisher ↗
PURPOSE: Integrin αvβ3 is an important structural and signaling protein of the plasma membrane of cancer cells and dividing blood vessel cells. The plastic extracellular domain of the protein binds to extracellular matri...
PURPOSE: Integrin αvβ3 is an important structural and signaling protein of the plasma membrane of cancer cells and dividing blood vessel cells. The plastic extracellular domain of the protein binds to extracellular matrix proteins and plasma membrane proteins, changing cell-cell interactions and generating intracellular signals that influence cell behavior. αvβ3 also contains a receptor for thyroid hormone and derivatives, including tetraiodothyroacetic acid (tetrac). MATERIALS AND METHODS: Human prostate cancer (PC3) cells were engrafted in the chicken chorioallantoic membrane model. The well-vascularized spheroidal xenografts were exposed to X-radiation in varying dosages (1-10 Gy) and in the presence and absence of an antibody that recognizes unliganded human β3 integrin monomer in the extended or open (activated) configuration. RESULTS: Radiation significantly increased activated β3 within 1 h (P < .001), a radiation response not previously reported. Incubation of cells with unmodified tetrac or tetrac covalently linked to a nanoparticle (Nanotetrac, NDAT) did not change basal activation state of the integrin monomer, but prevented radiation-induced activation of β3. CONCLUSIONS: Activation of the integrin in response to radiation is interpreted as a defensive response, perhaps leading to increased intercellular affinity and inhibition of cell division, a radioresistant state. Action of NDAT indicates that pharmacologic interventions in the radiation response of integrin β3 monomer and therefore of αvβ3 are feasible.
The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells.
Ahram M, Mustafa E, Abu Hammad S … +5 more , Alhudhud M, Bawadi R, Tahtamouni L, Khatib F, Zihlif M
Endocr Res · 2018 Aug · PMID 29578828 · Publisher ↗
PURPOSE: The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of...
PURPOSE: The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of these compounds is Cl-4AS-1. This study examined this compound more closely at the cellular and molecular levels. METHODS: Three different breast cancer cell lines were utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453 cells, and the triple negative, basal MDA-MB-231 cells. RESULTS: High and significant concordance between dihydrotestosterone (DHT) and Cl-4AS-1 in regulation of gene expression in MDA-MB-453 cells was found. However, some differences were noted including the expression of AR, which was upregulated by DHT, but not Cl-4AS-1. In addition, both DHT and Cl-4AS-1 caused a similar morphological change and reorganization of the actin structure of MDA-MB-453 cells into a mesenchymal phenotype. Treatment of cells with DHT resulted in induction of proliferation of MCF-7 and MDA-MB-453 cells, but no effect was observed on the growth of MDA-MB-231 cells. On the other hand, increasing doses of Cl-4AS-1 resulted in a dose-dependent inhibition on the growth of the three cell lines. This inhibition was a result of induction of apoptosis whereby Cl-4AS-1 caused a block in entry of cells into the S-phase followed by DNA degradation. CONCLUSIONS: These results indicate that although Cl-4AS-1 has characteristics of classical AR agonist, it has dissimilar properties that may make it useful in treating breast cancer.
Modifications in the spectrum of bone mass predictive factors with menopausal status.
Bilha SC, Branisteanu D, Buzduga C … +6 more , Constantinescu D, Cianga P, Anisie E, Gavrilovici C, Covic A, Ungureanu MC
Endocr Res · 2018 Aug · PMID 29528762 · Publisher ↗
PURPOSE: Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women. M...
PURPOSE: Fat mass (FM) is a source of adipocytokines, with both positive and negative bone consequences. We aimed to investigate the role of body composition and adipokines as predictive factors for bone mass in women. METHODOLOGY: This cross-sectional study included 93 women (38 premenopausal and 55 postmenopausal). Bone mineral density (BMD) and body composition were assessed by dual-energy X-ray absorptiometry. Serum levels of leptin, adiponectin, resistin, and also of the phosphocalcic markers parathormone and vitamin D were measured. RESULTS: Only lean mass (LM) was an independent predictor of BMD in premenopausal women (r = 0.381, p < 0.001 for femoral neck BMD, r = 0.2, p < 0.01 for whole-body BMD) in both unadjusted and age-adjusted models. The effect of total FM upon BMD became nonsignificant when LM was added to the models assessed. In postmenopausal women, although LM, trunk-to-leg fat ratio, and resistin were initially associated with BMD in unadjusted models, only the trunk-to-leg fat ratio independently predicted BMD at various sites (r = 0.171, p < 0.01 for lumbar BMD, r = 0.078, p < 0.05 for radius BMD, r = 0.094, p < 0.05 for whole-body BMD) after adjusting for age. CONCLUSIONS: While in premenopausal women the effect of LM upon bone is prevalent, after menopause, the fat distribution reflected by trunk-to-leg fat ratio is a major determinant of bone mass at different sites. Our study also stresses that the relationship between total FM and BMD is not mediated by adipokines in women irrespective of menopausal status and body composition, but it is largely mediated by LM only in young premenopausal women.
Vasoactive androgens: Vasorelaxing effects and their potential regulation of blood pressure.
Isidoro L, Ferrer M, Perusquía M
Endocr Res · 2018 Aug · PMID 29528756 · Publisher ↗
BACKGROUND: Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced...
BACKGROUND: Testosterone, 5α- and 5β-dihydrotestosterone (-DHT) induce an acute in vitro vasorelaxation and in vivo vasodepressor, hypotensive and antihypertensive responses. Our aim was to study whether androgen-induced blood pressure (BP) reduction is involved with a blockade of Ca influx through L-type voltage-operated calcium channels (L-VOCCs) and/or the signaling pathways of α-adrenoceptors to induce vasoconstriction, which are one of the major mechanisms of BP maintenance. MATERIALS AND METHODS: The relaxing potency and efficacy of each androgen in large conduit (thoracic aorta) and resistance (mesenteric) arteries from male hypertensive (SHR) and normotensive (WKY) rats were established. Blood vessels were isometrically recorded and precontracted with KCl or phenylephrine (Phe). RESULTS: Androgens induced concentration-dependent vasorelaxation in precontracted arteries from SHR and WKY rats. 5β-DHT was always the most potent vasorelaxant in arteries from SHR. The KCl-induced contraction resulted significantly more sensitive to androgen-induced vasorelaxation than the Phe-induced contraction. On Phe-induced contraction, 5β-DHT was more potent in the mesenteric artery than in the thoracic aorta. CONCLUSIONS: The vasorelaxation induced by androgens is mainly mediated by blocking L-VOCCs and in lesser extent by the blockade of multiple signaling pathways operative during α-adrenoceptor-induced vasoconstriction. 5β-DHT regulates vascular resistance and BP by mainly acting in the mesenteric arterial bed, which may explain its outstanding antihypertensive response previously reported.
Diabetic serum from older women increases adipogenic differentiation in mesenchymal stem cells.
Moseley KF, Doyle ME, Jan De Beur SM
Endocr Res · 2018 Aug · PMID 29521566 · Full text
BACKGROUND: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local e...
BACKGROUND: Paradoxically, elderly persons with type 2 diabetes mellitus (T2DM) fracture despite having higher bone density than nondiabetics. Systemic factors associated with aging and T2DM may have detrimental, local effects on the skeleton. One such factor could be by altering the microenvironment of the mesenchymal stem cells (MSCs), multipotent progenitors capable of differentiating into adipocytes or osteoblasts. METHODS: Sera were obtained from four participant groups (n = 40 total, 10 per group): (1) young women with normal glucose tolerance (NGTY), (2) postmenopausal women with NGT), (3) postmenopausal women with impaired glucose tolerance (IGT), and (4) postmenopausal women with T2DM. Sera were incubated with human MSCs for 14 days. Cell proliferation and apoptosis were measured using EdU and TUNEL labeling assays, respectively. MSC differentiation for each group was determined using osteogenic and adipogenic gene expression markers quantified by qRT-PCR, as well as Alizarin Red and Oil Red O staining. RESULTS: Expression of adipogenic genes was greater than twofold higher (P < 0.05) in MSCs cultured with T2DM sera compared to those incubated with NGTY, NGT, or IGT sera. The increase in adipogenic gene expression corresponded with increased Oil Red O staining. Despite the increased adipogenic differentiation of MSCs exposed to T2DM sera, cell proliferation and apoptosis rates as well as osteoblastic activity were not significantly different among the four conditions. CONCLUSIONS: Systemic, circulating factors in the serum of older women with T2DM may promote MSC differentiation into adipocytes versus osteoblasts. Increased differentiation of MSCs into adipocytes is one possible mechanism by which T2DM increases fracture risk.
MIBI scintigraphy of parathyroid adenomas: correlation with biochemical and histological markers.
Cordes M, Dworak O, Papadopoulos T … +2 more , Coerper S, Kuwert T
Endocr Res · 2018 Aug · PMID 29461127 · Publisher ↗
PURPOSE: In this study, we tested the hypothesis that MIBI-positive and MIBI-negative adenomas of parathyroid glands (APGs) have distinct biochemical and histological markers that could help differentiate MIBI-positive f...
PURPOSE: In this study, we tested the hypothesis that MIBI-positive and MIBI-negative adenomas of parathyroid glands (APGs) have distinct biochemical and histological markers that could help differentiate MIBI-positive from MIBI-negative APGs. PATIENTS AND METHODS: 40 patients with 41 APGs were included in the study. Patients were enrolled in the study after MIBI scintigraphy examinations had been carried out. Biochemical analyses included serum levels of calcium (Ca), intact parathyroid hormone (iPTH), and 25-hydroxyvitamin D3 (25-OH-D3). All patients had neck ultrasound and MIBI examinations. After surgical resection the APGs were examined histologically. RESULTS: In each of 39 patients one APG could be confirmed by histology, and in one patient, two contralateral APGs were identified. MIBI studies were positive in 73 % and negative in 27 % of the APGs. False-positive cases were not observed. MIBI-negative APGs were only present in patients with iPTH values below 150 pg/ml. In 82 % of MIBI negative studies oxyphilic cells were absent, and this cell type was present in only 18 % of MIBI negative cases (p < 0.001). Regarding cysts within the APGs, no differences were demonstrated between MIBI positive or negative studies (p = 0.32). Fat cells were seen in none of the MIBI -negative studies and in only 3 % of MIBI positive studies (p = 0.08). CONCLUSIONS: For APGs, MIBI positivity correlates with serum iPTH concentration. The absence of oxyphilic cells with large numbers of mitochondria in APGs contributes to MIBI negativity, probably because of the reduced binding sites for the radiotracer.
Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy.
Tiliscan C, Arama V, Mihailescu R … +7 more , Munteanu D, Iacob DG, Popescu C, Catana R, Negru A, Lobodan A, Arama SS
Endocr Res · 2018 Aug · PMID 29451987 · Publisher ↗
BACKGROUND: Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/lept...
BACKGROUND: Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). MATERIALS AND METHODS: We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women. CONCLUSION: Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy. ABBREVIATIONS: ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.
Occult urolithiasis in asymptomatic primary hyperparathyroidism.
Tay YD, Liu M, Bandeira L … +4 more , Bucovsky M, Lee JA, Silverberg SJ, Walker MD
Endocr Res · 2018 May · PMID 29400579 · Full text
OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk...
OBJECTIVE: Recent international guidelines suggest renal imaging to detect occult urolithiasis in all patients with asymptomatic primary hyperparathyroidism (PHPT), but data regarding their prevalence and associated risk factors are limited. We evaluated the prevalence and risk factors for occult urolithiasis. METHODS: Cross-sectional analysis of 96 asymptomatic PHPT patients from a university hospital in the United States with and without occult nephrolithiasis. RESULTS: Occult urolithiasis was identified in 21% of patients. Stone formers had 47% higher 24-hour urinary calcium excretion (p = 0.002). Although available in only a subset of patients (n = 28), activated vitamin D [1,25(OH)D] was 29% higher (p = 0.02) in stone formers. There was no difference in demographics, BMI, calcium or vitamin D intake, other biochemistries, renal function, BMD, or fractures. Receiver operating characteristic curves indicated that urinary calcium excretion and 1,25(OH)D had an area under the curve of 0.724 (p = 0.003) and 0.750 (p = 0.04), respectively. A urinary calcium threshold of >211mg/day provided a sensitivity of 84.2% and a specificity of 55.3% while a 1,25(OH)D threshold of >91pg/mL provided a sensitivity and specificity of 62.5% and 90.0% respectively for the presence of stones. CONCLUSION: Occult urolithiasis is present in about one-fifth of patients with asymptomatic PHPT and is associated with higher urinary calcium and 1,25(OH)D. Given that most patients will not have occult urolithiasis, targeted imaging in those most likely to have occult stones rather than screening all asymptomatic PHPT patients may be useful. The higher sensitivity of urinary calcium versus 1,25(OH)D suggests screening those with higher urinary calcium may be an appropriate approach.
Impact of admission serum calcium levels on mortality in hospitalized patients.
Cheungpasitporn W, Thongprayoon C, Mao MA … +3 more , Kittanamongkolchai W, Sakhuja A, Erickson SB
Endocr Res · 2018 May · PMID 29381079 · Publisher ↗
OBJECTIVES: To assess the relationship between admission serum calcium levels and in-hospital mortality in all hospitalized patients. METHODS: All adult hospitalized patients who had admission serum calcium levels availa...
OBJECTIVES: To assess the relationship between admission serum calcium levels and in-hospital mortality in all hospitalized patients. METHODS: All adult hospitalized patients who had admission serum calcium levels available between years 2009 and 2013 were enrolled. Admission serum calcium was categorized based on its distribution into six groups (<7.9, 7.9 to <8.4, 8.4 to <9.0, 9.0 to <9.6, 9.6 to <10.1, and ≥10.1 mg/dL). The odds ratio (OR) of in-hospital mortality by admission serum calcium, using the calcium category of 9.6-10.1 mg/dL as the reference group, was obtained by logistic regression analysis. RESULTS: 18,437 patients were studied. The lowest incidence of in-hospital mortality was associated with admission serum calcium within 9.6 to <10.1 mg/dL. A higher in-hospital mortality rate was observed in patients with serum calcium <9.6 and ≥10.1 mg/dL. Also, 38% and 33% of patients with admission serum calcium <7.9 and ≥10.1 mg/dL were on calcium supplements before admission, respectively. After adjusting for potential confounders, both serum calcium <8.4 and ≥10.1 mg/dL were associated with an increased risk of in-hospital mortality with ORs of 2.86 [95% confidence interval (CI) 1.98-4.17], 1.74 (95% CI 1.21-2.53), and 1.69 (95% CI 1.10-2.59) when serum calcium were within <7.9, 7.9 to <8.4, and ≥10.1 mg/dL, respectively. CONCLUSION: Hypocalcemia and hypercalcemia on admission were associated with in-hospital mortality. Highest mortality risk is observed in patients with admission hypocalcemia (<7.9 mg/dL). One-third of patients with hypercalcemia on admission were on calcium supplements.
Secondary and tertiary preventions of thyroid disease.
Azizi F, Mehran L, Hosseinpanah F … +2 more , Delshad H, Amouzegar A
Endocr Res · 2018 May · PMID 29319359 · Publisher ↗
INTRODUCTION: Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impa...
INTRODUCTION: Secondary and tertiary preventions are concerned with the recognition of the disease process in a very early stage and delay in progression to complete disease and minimization of complications and the impact of illness. METHODS: All articles related to secondary and tertiary prevention of thyroid diseases were reviewed. Using related key words, articles published between 2001 and 2015 were evaluated, categorized, and analyzed. RESULTS: In secondary prevention, congenital hypothyroidism and subclinical hypo and hyperthyroidism are equally important. Routine screening of patients with multinodular goiter by either ultrasonography or calcitonin is a controversial issue, while calcitonin assessments in medullary cancer and RET in family members are recommended. Screening of thyroid disease in pregnancy is limited to those with risk factors. Views regarding the importance of thyroid autoimmunity in secondary prevention are also presented. In tertiary prevention, prescribing excessive doses of levothyroxine, in the elderly in particular and appropriate care of all patients to avoid progression and complications are the key issues. CONCLUSION: Optimization of management of thyroid diseases requires timely screening, prevention of progression to more sever disease, optimal medical care, and avoidance of iatrogenic conditions.
All-cause and cardiovascular mortality associated with sulphonylurea and metformin therapy in type 2 diabetes.
Ioacara S, Guja C, Reghina A … +3 more , Martin S, Sirbu A, Fica S
Endocr Res · 2018 May · PMID 29308936 · Publisher ↗
PURPOSE: To test the hypothesis that cumulative exposure to sulphonylurea (SU) or metformin (MET) have different effects on mortality when taken as a replacement or add-on of one for the other. METHODS: All consecutive d...
PURPOSE: To test the hypothesis that cumulative exposure to sulphonylurea (SU) or metformin (MET) have different effects on mortality when taken as a replacement or add-on of one for the other. METHODS: All consecutive diabetes patients aged over 20 years were screened at their first diabetes outpatient visit between 2001 and 2008 (n = 79869). Only patients on MET (n = 11374) or SU (n = 18502) monotherapy were retained. All patients were followed up for death until December 31, 2011, but censored at first exposure to anything else besides MET/SU. Adjusted time-dependent Cox regression and competing risk regression analysis, with daily updates of treatment modalities were performed. RESULTS: Mean age was 62.1 ± 11.2 years and follow-up was 4.6 ± 3.2 years (138496 person-years). Adjusted all-cause and cardiovascular mortality rates were significantly higher in MET as compared with SU group. All-cause mortality hazard ratios (HR) for cumulative time exposure were as follows: HR 0.956 (95%CI 0.951-0.962, p < 0.001) for SU added to MET, HR 1.092 (95%CI 1.087-1.096, p < 0.001) for SU replacing MET, HR 0.979 (95%CI 0.975-0.983, p < 0.001) for MET added to SU, and HR 1.127 (95%CI 1.118-1.136, p < 0.001) for MET replacing SU. CONCLUSION(S): The effect on all-cause mortality was beneficial for MET+SU combined therapy, but deleterious for either SU replacing MET, or MET replacing SU. There were no major outcome differences when analyzing individual SU, or specific mortality.
Association between anemia at three different time points and new-onset diabetes after kidney transplantation--a retrospective cohort study.
Grossman A, Ayalon-Dangur I, Cooper L … +4 more , Shohat T, Rahamimov R, Mor E, Gafter-Gvili A
Endocr Res · 2018 May · PMID 29300115 · Publisher ↗
PURPOSE: Anemia has been reported to be associated with diabetes, but the association between new-onset diabetes after transplantation (NODAT) and anemia has not been reported. METHODS: Patients who underwent kidney tran...
PURPOSE: Anemia has been reported to be associated with diabetes, but the association between new-onset diabetes after transplantation (NODAT) and anemia has not been reported. METHODS: Patients who underwent kidney transplantation and did not have diabetes prior to transplantation were included in this study. Hemoglobin levels and the prevalence of anemia (hemoglobin <12 g/dL in females and <13 g/dL in males) were evaluated at three time points (prior to transplantation, 6 months following transplantation or 1 month before the development of NODAT, 2 years following transplantation, or following the development of NODAT) and were compared between those who developed NODAT and those who did not. Variables associated with the development of anemia were compared between the two groups. RESULTS: A total of 266 kidney transplant recipients were included, of which 71 (27%) developed NODAT during the time of the follow-up. Hemoglobin and hematocrit levels and the prevalence of anemia were similar in those with and without NODAT at all three time points evaluated. Ferritin levels, prior to transplantation and mean corpuscular volume (MCV) posttransplantation post-NODAT development, were slightly but significantly lower in those with NODAT, although both were within the normal range. CONCLUSIONS: Pretransplantation ferritin levels and posttransplantation post-NODAT development MCV are inversely associated with the development of NODAT in kidney transplants.
The effect of weight loss on body composition, serum bone markers, and adipokines in prepubertal obese children after 1-year intervention.
Gajewska J, Ambroszkiewicz J, Klemarczyk W … +3 more , Chełchowska M, Weker H, Szamotulska K
Endocr Res · 2018 May · PMID 29192796 · Publisher ↗
UNLABELLED: Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied t...
UNLABELLED: Purpose/Aim: The influence of weight loss on bone turnover and bone quality in childhood remains controversial, but it may implicate interactions between adiposity and bone metabolism. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. MATERIALS AND METHODS: We determined serum leptin, soluble leptin receptor, adiponectin, bone alkaline phosphatase (BALP), C-terminal telopeptide of type I collagen (CTX-I), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), sclerostin, body composition, and bone mineral density (BMD) in 40 obese prepubertal children before and after therapy. The control group, matched for sex and age, consisted of 40 non-obese children. RESULTS: We found that values of the total body less head-bone mineral content (TBLH-BMC) and TBLH-BMD were significantly increased, but TBLH-BMD Z-score was decreased by 25% (p = 0.002) in obese children with weight loss after therapy. We observed increases of CTX-I to OC ratio (p = 0.009), and Gla-OC concentrations (p = 0.049). Changes in TBLH-BMD Z-score in patients were positively correlated with changes in BMI Z-score (p = 0.001), percentage of fat mass (p = 0.004), and BALP activity (p = 0.01). Changes in BALP activity were negatively correlated (p < 0.001) with changes in adiponectin concentrations, while changes in sclerostin levels were positively correlated (p = 0.001) with leptin changes. CONCLUSIONS: We suggest that alterations in adipokines metabolism were associated with a lower rate of bone mineral accrual as a result of decreased bone formation rather than increased bone resorption. The lower rate of bone mass accrual in weight losing children may be an effect of reduced BALP levels related to increase in adiponectin levels.
Reduced insulin sensitivity in differentiated thyroid cancer patients with suppressed TSH.
De Melo TG, Souza AL, Ficher E … +4 more , Fernandes AM, Montali Da Assumpção LV, Monte Alegre S, Zantut-Wittmann DE
Endocr Res · 2018 May · PMID 29083246 · Publisher ↗
OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on in...
OBJECTIVE: TSH-suppression is a therapy for thyroid cancer management, but it may lead to adverse effects, which should be balanced with its benefits. Previous studies evaluating the consequences of TSH suppression on insulin sensitivity have only been done with indirect techniques, and results were controversial. Therefore, we aimed to assess insulin sensitivity in patients with thyroid cancer and suppressed thyroid-stimulating hormone (TSH) with the most appropriate direct method (hyperinsulinemic-euglycemic clamp) in order to get a more conclusive response about the topic. METHODS: A group of 20 non-obese and non-diabetic thyroid cancer patients with suppressed TSH underwent a hyperinsulinemic-euglycemic clamp to evaluate insulin sensitivity. Their results were compared to the results of a sex and body mass index (BMI) -paired control group composed of 20 healthy volunteers. RESULTS: Patients were all female, aged 36.8 ± 10.2 years-old, with mean TSH 0.1 ± 0.1 μIU/mL and mean BMI 26.2 ± 3.3 kg/m. Insulin sensitivity, determined by the insulin-stimulated glucose uptake (M-value), was lower in the patients group (4.2 ± 1.6 mg/min*kg versus 5.8 ± 1.7, age-adjusted p-value = 0.0205). CONCLUSION: This study shows for the first time that subclinical thyrotoxicosis in patients with thyroid cancer is associated with insulin resistance, as measured by hyperinsulinemic-euglycemic clamp technique. Such finding may be taken into consideration by clinicians when balancing risks and benefits of TSH-suppression therapy in thyroid cancer patients.
Body weight predicts Nicotinamide N-Methyltransferase activity in mouse fat.
Rudolphi B, Zapp B, Kraus NA … +3 more , Ehebauer F, Kraus BJ, Kraus D
Endocr Res · 2018 Feb · PMID 29035138 · Publisher ↗
AIM: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy homeostasis in adipose tissue. NNMT expression is higher in obese mice than in lean mice, and NNMT knockdown prevents diet-induced obesity. Litt...
AIM: Nicotinamide N-methyltransferase (NNMT) is a novel regulator of energy homeostasis in adipose tissue. NNMT expression is higher in obese mice than in lean mice, and NNMT knockdown prevents diet-induced obesity. Little is known about the regulation of enzyme activity during the development of obesity. The aim of this study was to analyze NNMT activity in tissues of mice with incipient and established obesity. METHODS: A fluorescence-based, sensitive, low-volume, high-throughput method was developed to assay NNMT activity. C57BL/6 mice were fed a high-fat diet for 4 weeks (incipient obesity) and for 12 weeks (established obesity). Tissues and serum were harvested and analyzed. RESULTS: NNMT activity was highest in subcutaneous white fat (55.0 µU/mg), followed by epididymal white fat (35.6 µU/mg), brown adipose tissue (7.8 µU/mg), liver (7.6 µU/mg), and lung (7.3 µU/mg). Little activity was detected in heart, skeletal muscle, and kidney. No activity was found in serum samples. Body weight predicted NNMT activity in white fat, but not in brown fat or any other tissue, and only in incipient obesity. With established obesity, this association was lost. CONCLUSIONS: As obesity develops, body weight predicts NNMT activity in white adipose tissue, but not in any other tissue, consistent with a specific role of adipose-tissue NNMT in the regulation of body weight.
Factors influencing the outcome from ultrasonography-guided fine-needle aspiration of benign thyroid cysts and partially cystic thyroid nodules: A multicenter study.
Lim HK, Kim DW, Baek JH … +4 more , Huh JY, Ryu JH, Sung JY, Park SH
Endocr Res · 2018 May · PMID 29035129 · Publisher ↗
PURPOSE: The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FN...
PURPOSE: The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FNA of the cystic component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and to evaluate the factors influencing the outcome. METHODS: From June to December 2013, seven radiologists at seven institutions prospectively performed US-FNA on 320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least one follow-up US examination following US-FNA of the cystic component at each institution by the same radiologist. A variety of factors, including US features of cystic thyroid nodules, the characteristics of the aspirates, and the follow-up US findings, were analyzed. RESULTS: Of 179 cystic thyroid nodules, there were 53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies were detected. On follow-up US, the mean size reduction rate of the cystic component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to the response group. On univariate analysis, the degree of aspiration and time interval between US-FNA and the final follow-up US showed the significant differences between the response and no response groups. On multivariate analysis, the only factor that influenced the outcome was the nodule type. The cystic component's positive response rate after simple aspiration was higher in the thyroid cysts than in the PCTNs. CONCLUSIONS: US-FNA may be effective at collapsing the cystic components of benign thyroid cysts and PCTNs.
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