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  • Metabolic syndrome is the key determinant of impaired vaginal lubrication in women with chronic spinal cord injury
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-25
    S. D’Andrea, C. Castellini, V. Paladino, M. Totaro, G. Felzani, S. Francavilla, F. Francavilla, A. Barbonetti

    Abstract Purpose Spinal cord injury (SCI) affects sexual health of both male and female, but little attention has been given to sexuality of SCI women. Similar to penile erection, vaginal lubrication represents a neurovascular event and then both denervation and vascular damage might contribute to its impairment. Nevertheless, the relative weight of lesion location/degree and vascular risk factors in determining hypolubrication in women with SCI has not yet been investigated. The aim of this study was to recognize among putative determinants of poor sexual arousal in women with SCI, neurogenic and vascular/metabolic independent predictors of vaginal hypolubrication. Methods Twenty-eight consecutive female patients admitted to a rehabilitation program because of chronic SCI (≥ 1 year) underwent clinical and biochemical evaluations, including assessment of vaginal lubrication by the Female Sexual Function Index (FSFI). As, in people with SCI, waist circumference overestimates visceral fat mass due to abdominal muscle paralysis, metabolic syndrome (MetS) was defined according to specific criteria proposed for SCI population: BMI ≥ 22 kg/m2 and two or more of the following: triglycerides ≥ 150 mg/dL (or actual treatment), HDL < 50 mg/dL, hypertension (or actual treatment), fasting glucose ≥ 100 mg/dL or diabetes mellitus type 2. Results A FSFI lubrication sub-score < 3.6, suggestive for impaired vaginal lubrication, was exhibited by 53.7% of the study population. When compared to the group with normal lubrication, a significantly higher proportion of these women had paraplegia (93.3% vs 38.5%, p = 0.003) and met the SCI-specific criteria for MetS (73.4% vs 7.6%, p = 0.0006), whereas, no significant differences were found between the two groups in the proportion of women exhibiting the single components of MetS. At the multiple logistic regression analysis, only the presence of MetS exhibited a significant independent association with impaired vaginal lubrication (OR = 3.1, 95% CI 1.2, 5.8, p = 0.01). Conclusions In women with SCI, a clustering of modifiable vascular/metabolic risk factors, constituting the MetS, could contribute to sexual dysfunctions by affecting the vaginal lubrication, independently of the level of the spinal cord lesion.

    更新日期:2020-01-26
  • The triglycerides and glucose index is associated with cardiovascular risk factors in metabolically obese normal-weight subjects
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-22
    G. Morales-Gurrola, L. E. Simental-Mendía, F. X. Castellanos-Juárez, J. M. Salas-Pacheco, F. Guerrero-Romero

    Abstract Purpose The aim of this study was to determine whether the triglycerides and glucose (TyG) index is associated with the presence of metabolically obese normal-weight (MONW) phenotype and related cardiovascular risk factors. Methods Apparently healthy men and non-pregnant women aged 20–65 years were enrolled in a population-based cross-sectional study. Overweight, obesity, smoking, alcohol consumption, pregnancy, diagnosis of hypertension, diabetes, cardiovascular disease, liver disease, renal disease, malignancy, and medical treatment were exclusion criteria. Subjects were allocated into the MONW or normal-weight groups. MONW phenotype was defined by normal weight and the presence of at least one of the following cardiovascular risk factors: elevated blood pressure, hyperglycemia, hypertriglyceridemia, and low HDL cholesterol. Results A total of 542 subjects were enrolled and allocated into the MONW (n = 354) and normal-weight (n = 188) groups. The adjusted logistic regression analysis showed that the elevated TyG index is significantly associated with the presence of MONW phenotype (OR = 11.14; 95% CI 6.04–20.57), hyperglycemia (OR = 3.18; 95% CI 1.95–5.21), hypertriglyceridemia (OR = 399.19; 95% CI 94.01–1694.98), and low HDL-C (OR = 2.60; 95% CI 1.74–3.87), but not with elevated blood pressure (OR = 1.55; 95% CI 0.93–2.60). Conclusion Results of this study support that the TyG index may be a useful indicator to detect MONW phenotype and associated cardiovascular risk factors.

    更新日期:2020-01-23
  • ICH3, a selective alpha7 nicotinic acetylcholine receptor agonist, modulates adipocyte inflammation associated with obesity
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-21
    G. Scabia, R. Cancello, C. Dallanoce, S. Berger, C. Matera, A. Dattilo, A. Zulian, I. Barone, G. Ceccarini, F. Santini, M. De Amici, A. M. Di Blasio, M. Maffei

    Abstract Purpose The alpha7 nicotinic acetylcholine receptor (α7nAChR), involved in the modulation of inflammation and insulin sensitivity, is downregulated in white adipose tissue (WAT) of obese patients. This study aims to test the ability of a selective synthetic α7nAChR agonist, the spirocyclic Δ2-isoxazoline derivative (R)-(−)-ICH3 (ICH3), to counteract acute inflammation and obesity-associated modifications in WAT. Methods We employed the LPS-septic shock murine model, human primary adipocytes and diet-induced obese (DIO) mice. Inflammatory factor expression was assessed by ELISA and quantitative real-time PCR. Flow cytometry was employed to define WAT inflammatory infiltrate. Insulin signaling was monitored by quantification of AKT phosphorylation. Results In the septic shock model, ICH3 revealed antipyretic action and reduced the surge of circulating cytokines. In vitro, ICH3 stimulation (10 µM) preserved viability of human adipocytes, decreased IL-6 mRNA (P < 0.05) and blunted LPS-induced peak of TNFα (P < 0.05) and IL-6 (P < 0.01). Chronic administration of ICH3 to DIO mice was associated with lower numbers of CD8+ T cells (P < 0.05) and to changed WAT expression of inflammatory factors (Hp, P < 0.05; CD301/MGL1, P < 0.01; Arg-1, P < 0.05). As compared to untreated, ICH3 DIO mice exhibited improved insulin signaling in the skeletal muscle (P < 0.01) mirrored by an improved response to glucose load (ipGTT: P < 0.05 at 120 min). Conclusions We proved that ICH3 is an anti-inflammatory drug, able to reduce inflammatory cytokines in human adipocytes and to blunt the effects of obesity on WAT inflammatory profile, on glucose tolerance and on tissue insulin sensitivity.

    更新日期:2020-01-22
  • Comprehensive transcriptomic analysis of papillary thyroid cancer: potential biomarkers associated with tumor progression
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-21
    N. Hosseinkhan, M. Honardoost, K. Blighe, C. B. T. Moore, M. E. Khamseh

    Abstract Purpose Identification of stage-specific prognostic/predictive biomarkers in papillary thyroid carcinoma (PTC) could lead to its more efficient clinical management. The main objective of this study was to characterize the stage-specific deregulation in genes and miRNA expression in PTC to identify potential prognostic biomarkers. Methods 495 RNASeq and 499 miRNASeq PTC samples (stage I–IV) as well as, respectively, 56 and 57 normal samples were retrieved from The Cancer Genome Atlas (TCGA). Differential expression analysis was performed using DESeq 2 to identify deregulation of genes and miRNAs between sequential stages. To identify the minority of patients who progress to higher stages, we performed clustering analysis on stage I RNASeq data. An independent PTC RNASeq data set (BioProject accession PRJEB11591) was also used for the validation of the results. Results LTF and PLA2R1 were identified as two promising biomarkers down-regulated in a subgroup of stage I (both in TCGA and in the validation data set) and in the majority of stage IV of PTC (in TCGA data set). hsa-miR-205, hsa-miR-509-2, hsa-miR-514-1 and hsa-miR-514-2 were also detected as up-regulated miRNAs in both PTC patients with stage I and stage III. Hierarchical clustering of stage I samples showed substantial heterogeneity in the expression pattern of PTC indicating the necessity of categorizing stage I patients based on the expressional alterations of specific biomarkers. Conclusion Stage I PTC patients showed large amount of expressional heterogeneity. Therefore, risk stratification based on the expressional alterations of candidate biomarkers could be an important step toward personalized management of these patients.

    更新日期:2020-01-22
  • The clinical phenotype of Graves' disease occurring as an isolated condition or in association with other autoimmune diseases.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    M Rotondi,C Virili,S Pinto,F Coperchini,L Croce,N Brusca,M Centanni,L Chiovato

    PURPOSE Graves' disease (GD) can present as an isolated disease (iGD) or in association with other autoimmune diseases (aGD). The aim of this study, performed in two Endocrine referral centers settled in different geographical areas of Italy, was to compare the anthropometric, clinical, and biochemical phenotype of iGD patients with that of the aGD ones. METHODS Clinical history, physical examination data, serum levels of TSH, FT4, FT3, thyroglobulin (TgAb), thyroid-peroxidase (TPOAb) and TSH-receptor (TRAb) antibody, presence of Graves' orbitopathy (GO), and thyroid ultrasound examination at disease diagnosis were recorded. RESULTS 68 aGD and 136 iGD patients were consecutively recruited. At diagnosis, aGD and iGD patients did not differ for F/M ratio, age at presentation, thyroid function parameters, serum levels of TRAb, TgAb, TPOAb, presence of GO, and thyroid volume. The serum levels of TRAb were strongly correlated with the circulating concentrations of both FT3 (ρ = 0.667; p < 0.0001) and FT4 (ρ = 0.628; p < 0.001) in iGD patient, but not in the aGD ones (FT3: ρ = 0.231; p = 0.058; FT4: ρ = 0.096; p = 0.435). Compared with iGD patients, the aGD ones displayed a higher rate of transition from the previous hypothyroidism to hyperthyroidism (χ2 = 6.375; p = 0.012). CONCLUSION Despite similar anthropometric, clinical, and biochemical features at diagnosis, aGD patients display a higher rate of transition from a thyroid functional status to the other as compared with iGD patients.

    更新日期:2020-01-21
  • Clinical and genetic analysis of idiopathic normophosphatemic tumoral calcinosis in 19 patients.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    Q-Y Zuo,X Cao,B-Y Liu,D Yan,Z Xin,X-H Niu,C Li,W Deng,Z-Y Dong,J-K Yang

    PURPOSE Tumoral calcinosis is a rare clinicopathological entity characterized by ectopic soft-tissue calcification, typically periarticular. Normophosphatemic tumoral calcinosis is seldom reported in East Asian populations, and the preoperative diagnosis is often elusive. This study was performed to characterize the clinical profile of normophosphatemic tumoral calcinosis and investigate the presence of the SAMD9 gene mutation. METHODS The clinical features, pathological examination findings, and outcomes of 19 subjects were retrospectively reviewed. All patients were analyzed for SAMD9 gene mutation using paraffin-embedded tumoral calcinosis specimens. RESULTS Nineteen subjects were analyzed (7 males, 12 females). Their mean age at surgery, mean age at symptom onset, and median disease duration was 51.9 ± 17.3 (range 7-75) years, 49.1 ± 17.2 (range 7-74) years, and 1.3 (interquartile range 0.5-3.0) years, respectively. Lesions were located in the hand in 8 (42.1%) subjects; wrist in 5 (26.3%); shoulder in 2 (10.5%); and hip, knee, buttock, and scrotum in 1 (5.3%) subject each. The lesions in 17 (89.5%) subjects were located around the joints [small joints (hand and wrist) in 13 (68.4%) and large joints (shoulder, hip, and knee) in 4 (21.1%)]. Lesions occurred in the upper limbs in 15 (78.9%) subjects and in the lower limbs in 2 (10.5%). Multiple-lesion involvement (distal right index finger and middle finger) occurred in one (5.3%) subject. Symptoms included pain in 15 (78.9%) subjects, impaired mobility in 5 (26.3%), swelling in 5 (26.3%), numbness in 2 (10.5%), and an asymptomatic mass in 2 (10.5%). The serum inorganic phosphorus concentration was normal in all 19 subjects (mean 1.17 ± 0.15 mmol/L). The serum calcium concentration was normal in 18 subjects and low in 1. The serum alkaline phosphatase concentration was normal in all 19 subjects. Pathological examination indicated multiple nodules of calcified materials that manifested an amorphous or granular blue-purple crystal and were surrounded by proliferation of mononuclear or multinuclear macrophages, osteoclastic-like giant cells, fibroblasts, and chronic inflammatory cells. Notably, different phases of pathological manifestations were observed in the same microscopic field. During follow-up (0.5-65.0 months), no recurrence of tumoral calcinosis was observed in 18 (94.7%) subjects, but 1 subject developed in situ recurrence of an asymptomatic subcutaneous mass after 6 months postoperatively. Genetic analysis in all 19 subjects revealed no SAMD9 gene mutations. CONCLUSIONS Most subjects were females and developed calcinosis in adulthood. Small joints (hand and wrist) and the upper limbs were frequently involved. The presence of different phases of pathological features in the same subject suggests that about half of the study participants had been misdiagnosed with another condition (such as gout, osteoarthritis, etc.). Complete surgical excision led to cure without recurrence during follow-up in majority of the study participants.

    更新日期:2020-01-21
  • Genetic interaction analysis of VEGF-A rs3025039 and VEGFR-2 rs2071559 identifies a genetic profile at higher risk to develop nodular goiter.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    A Molinaro,P Orlandi,F Niccolai,P Agretti,G De Marco,E Ferrarini,C Di Cosmo,P Vitti,P Piaggi,T Di Desidero,G Bocci,M Tonacchera

    CONTEXT Nodular goiter in patients from areas of iodine deficiency is due to the growth of follicular and endothelial cells, involving different vascular-related growth factors in its pathogenesis. OBJECTIVE The aim of our study was to examine the association of known single polymorphisms of vascular endothelial growth factor-A [VEGF-A], VEGF receptor-2 [VEGFR-2] and hypoxia-inducible factor-1α [HIF-1α] genes or their genetic interactions with the risk of nodular goiter development. PATIENTS AND METHODS 116 normal subjects, without any thyroid disease, and 108 subjects with nodular goiter [subjects with goiter and at least one thyroid nodule of > 1 cm of maximum size and in absence of signs of autoimmunity] were selected from a homogeneous population living in a mild iodine deficiency geographic area. Analyses were performed on germline DNA obtained from blood samples and VEGF-A rs3025039, VEGFR-2 rs2071559, and HIF-1αrs11549465 SNPs were investigated by real-time PCR technique. The multifactor dimensionality reduction [MDR] methodology was applied to investigate the genetic interaction between SNPs. Hardy-Weinberg equilibrium was performed. RESULTS None of the studied polymorphisms were individually associated with a higher risk to develop nodular goiter [P > 0.05]. The combination of the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms had the highest accuracy of 0.58 [P = 0.018] and the interaction of some genotypes was significantly associated with the risk of nodular goiter development. CONCLUSIONS Our results support a genetic interaction between the VEGF-A rs3025039 and VEGFR-2 rs2071559 polymorphisms as a predictor of the risk to develop nodular goiter in subjects coming from an area with mild iodine deficiency.

    更新日期:2020-01-21
  • Immunohistochemical analysis of human orbital tissue in Graves' orbitopathy.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    Y P Hai,A C H Lee,L Frommer,T Diana,G J Kahaly

    PURPOSE Immunohistochemistry of orbital tissues offers a correlation between the microscopic changes and macroscopic clinical manifestation of Graves' orbitopathy (GO). Summarizing the participation of different molecules will help us to understand the pathogenesis of GO. METHODS The pertinent and current literature on immunohistochemistry of human orbital tissue in GO was reviewed using the NCBI PubMed database. RESULTS 33 articles comprising over 700 orbital tissue samples were included in this review. The earliest findings included the demonstration of HLA-DR and T cell (to a lesser extent B cell) markers in GO orbital tissues. Subsequent investigators further contributed by characterizing cellular infiltration, confirming the presence of HLA-DR and TSHR, as well as revealing the participation of cytokines, growth factors, adhesion molecules and miscellaneous substances. HLA-DR and TSHR are over-expressed in orbital tissues of GO patients. The inflammatory infiltration mainly comprises CD4 + T cells and macrophages. Cytokine profile suggests the importance of Th1 (especially in early active phase) and Th17 immunity in the pathogenesis of GO. Upregulation of proinflammatory/profibrotic cytokines, adhesion molecules and growth factors finally culminate in activation of orbital fibroblasts and perpetuation of orbital inflammation. The molecular status of selected parameters correlates with the clinical presentation of GO. CONCLUSION Further investigation is warranted to define precisely the role of different molecules and ongoing search for new players yet to be discovered is also important. Unfolding the molecular mechanisms behind GO will hopefully provide insights into the development of novel therapeutic strategies and optimize our clinical management of the disease.

    更新日期:2020-01-21
  • Final height in growth hormone-deficient childhood cancer survivors after growth hormone therapy.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    G Rodari,A Cattoni,A Albanese

    PURPOSE Growth hormone deficiency (GHD) is the most prevalent hypothalamic-pituitary (HP) disorder found in childhood cancer survivors (CCS). The published studies assessing GHD in CCS concluded that recombinant human GH (rhGH) does not restore final height (FH) to that predicted from mid-parental height (MPH). Thus, wider analyses on final height outcomes after rhGH in CCS are needed. METHODS Retrospective study on final height (FH) in 87 CCS treated with rhGH. Patients were divided into: Group A (n =48) who underwent cranial radiotherapy or had non-irradiated tumours of HP area, and B (n =39) who were treated with craniospinal or total body irradiation (TBI). 19/87 patients with central precocious/early puberty also received GnRH analogues. RESULTS Height (HT) gain after 1 and 2 years of rhGH was 0.38 ± 0.35 SDS and 0.18 ± 0.30 SDS, respectively (P < 0.0001); mean FH was in the normal range (- 0.85 ± 1.34 SDS), though not significantly different from HT SDS at baseline. 67% overall failed to reach MPH especially in Group B (P < 0.0001). However, height loss (HT SDS-MPH SDS) at FH improved or remained stable compared to baseline in 26/45 patients (58%). On stepwise regression analysis, major determinants of FH were HT at baseline (P < 0.0001) and delay before start of rhGH (P = 0.012). There was no significant difference in FH when GnRHa was added to rhGH. CONCLUSION rhGH and GnRH analogues therapy, when indicated, though failing to induce catch-up growth, prevented further height loss leading to a FH within the normal range but still below MPH, this latter being statistically significant in children who received craniospinal and TBI.

    更新日期:2020-01-21
  • Whole exome sequencing in familial isolated primary hyperparathyroidism.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-09-06
    F Cetani,E Pardi,P Aretini,F Saponaro,S Borsari,L Mazoni,M Apicella,P Civita,M La Ferla,M A Caligo,F Lessi,C M Mazzanti,L Torregossa,A Oppo,C Marcocci

    PURPOSE Familial isolated hyperparathyroidism (FIHP) is a rare inherited disease accounting for 1% of all cases of primary hyperparathyroidism (PHPT). It is genetically heterogeneous being associated with mutations in different genes, including MEN1, CDC73, CASR, and recently GCM2. The aim of the study was to further investigate the molecular pathogenesis in Italian FIHP kindreds. METHODS We used whole exome sequencing (WES) in the probands of seven unrelated FIHP kindreds. We carried out a separate family-based exome analysis in a large family characterized by the co-occurrence of PHPT with multiple tumors apparently unrelated to the disease. Selected variants were also screened in 18 additional FIHP kindreds. The clinical, biochemical, and pathological characteristics of the families were also investigated. RESULTS Three different variants in GCM2 gene were found in two families, but only one (p.Tyr394Ser), already been shown to be pathogenic in vitro, segregated with the disease. Six probands carried seven heterozygous missense mutations segregating with the disease in the FAT3, PARK2, HDAC4, ITPR2 and TBCE genes. A genetic variant in the APC gene co-segregating with PHPT (p.Val530Ala) was detected in a family whose affected relatives had additional tumors, including colonic polyposis. CONCLUSION We confirm the role of GCM2 germline mutations in the pathogenesis of FIHP, although at a lower rate than in the previous WES study. Further studies are needed to establish the prevalence and the role in the predisposition to FIHP of the novel variants in additional genes.

    更新日期:2020-01-21
  • Dysregulated mitogen-activated protein kinase pathway mediated cell cycle disruption in sporadic parathyroid tumors.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    A K Arya,P Singh,U N Saikia,N Sachdeva,D Dahiya,A Behera,S D Rao,S K Bhadada

    OBJECTIVES The study was designed to evaluate expression profiling of mitogen-activated protein kinase (MAPK) signalling pathway genes in sporadic parathyroid adenoma. METHODS Expression of MAPK signalling pathway genes including activated transcription factors and cell cycle regulatory genes was analysed by real-time PCR- based array in parathyroid adenoma (N = 20) and normal parathyroid tissue (N = 4). RESULTS MAPK signalling pathway as studied by PCR array revealed that a total of 22 genes were differentially expressed (≥ twofold change, p ≤ 0.05) in parathyroid adenoma. Up-regulated genes were ARAF, MAPK12, CREBBP, MYC, HSPB1, HRAS, CDK4, CCND1, and E2F1, and down-regulated genes were MAP4K1, DLK1, MAP3K4, MAPK10, MAPK8, ATF2, SMAD4, MEF2C, LAMTOR3, FOS, CDKN2A CDKN2B, and RB1. The present study revealed that ERK1/2 signalling pathway with up-regulation of HRAS, ARAF, and MEK1 genes and up-regulation of positive regulators of cell cycle (CCND1, CDK4, and E2F1) and down-regulation negative regulators of cell cycle (CDKN2A, CDKN2B, and RB1) made highly dysregulated MAPK signalling pathway in parathyroid adenoma. Expression of CDK4 was positively associated with plasma PTH level (r = 0.60, p = 0.04) and tumor weight (r = 0.80, p = 0.02) of the adenoma patients, respectively. Expression of CDKN2A was correlated negatively with PTH level (r = - 0.52, p = 0.04) of the adenoma patients. CONCLUSION The current study revealed that ERK pathway and associated cell cycle regulator genes are dysregulated in sporadic parathyroid adenoma.

    更新日期:2020-01-21
  • Untreated adult GH deficiency is not associated with the development of metabolic risk factors: a long-term observational study.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    V Gasco,L Roncoroni,M Zavattaro,C Bona,A Berton,E Ghigo,M Maccario,S Grottoli

    PURPOSE Uncertainties exist about the predictors of the severity of the clinical picture of GH deficiency (GHD) syndrome. Aim of the study was to evaluate, in adult patients with GHD, the predictors of the development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis. METHODS We retrospectively studied 327 adult patients (age 47.1 ± 17.1 years) with untreated severe GHD (mean follow-up 110.9 ± 56.8 months). GHD was defined by GHRH + arginine test using BMI cut-offs. The possible development of hypercholesterolemia, hypertension, diabetes mellitus, and osteoporosis was investigated by Kaplan-Meier survival analysis. For each clinical outcome, either a univariate or multivariate analysis according to the Cox proportional-hazards model was performed to identify those factors that were associated with the development of the event. RESULTS GH secretion parameters were not associated with the outcomes. Hypercholesterolemia was positively and negatively predicted by a BMI ≥ 30 kg/m2 (HR 2.50, p 0.00) and the dose of l-thyroxine possibly in place (HR 0.98, p 0.02), respectively. Hypertension was positively predicted by a BMI ≥ 30 kg/m2 (HR 2.64, p 0.00) and IGF-I SDS values (HR 2.26, p 0.00). Diabetes mellitus was positively predicted by hypertension (HR 11.76, p 0.01). Osteoporosis was positively and negatively predicted by hypercholesterolemia (HR 3.25, p 0.01) and hypertension (HR 0.21, p 0.00), respectively. CONCLUSIONS The severity of the impairment of GH secretion does not predict the development of the clinical picture of GHD syndrome: untreated adult GHD does not increase the development of metabolic risk factors in hypopituitaric patients.

    更新日期:2020-01-21
  • Alemtuzumab-induced thyroid events in multiple sclerosis: a systematic review and meta-analysis.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    L Scappaticcio,M Castellana,C Virili,G Bellastella,M Centanni,S Cannavò,A Campennì,R M Ruggeri,L Giovanella,P Trimboli

    PURPOSE Autoimmune thyroid events (ATEs) are common side effects after alemtuzumab (ALZ) therapy in patients with multiple sclerosis (MS). Our purpose was to reach more robust evidence on prevalence and outcome of the spectrum of alemtuzumab-induced autoimmune thyroid events in patients with multiple sclerosis. METHODS PubMed and Scopus were systematically searched through July 2019. Studies dealing with patients without personal history of thyroid dysfunctions and affected by MS treated with ALZ and reporting ATEs were selected. Data on prevalence and outcome of ATEs were extracted. A proportion of meta-analysis with random-effects model was performed. RESULTS Considering the overall pooled number of 1362 MS patients treated with ALZ (seven included studies), a 33% prevalence of newly diagnosed ATEs was recorded. Among all ATEs, Graves' disease (GD) was the most represented [63% of cases, 95% confidence interval (CI) 52-74%], followed by Hashimoto thyroiditis (15%, 95% CI 10-22%). Interestingly, GD showed a fluctuating course in 15% of cases (95% CI 8-25%). Of all GD, 12% (95% CI 2-42%) likely had spontaneous remission, 56% (95% CI 34-76%) required only antithyroid drugs, 22% (95% CI 13-32%) needed additional RAI, and 11% (95% CI 0.9-29%) underwent definitive surgery. CONCLUSION Among different categories of ATEs, Graves' hyperthyroidism was the most common thyroid dysfunction, occurring in more than half of cases. Antithyroid drugs should represent the first-line treatment for ALZ-induced GD patients. However, alemtuzumab-induced GD could not be considered as having a more favourable outcome than conventional GD, given the substantial chance to encounter a fluctuating and unpredictable course.

    更新日期:2020-01-21
  • The functioning side of the pancreas: a review on insulinomas.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    I Maggio,V Mollica,N Brighi,G Lamberti,L Manuzzi,A D Ricci,D Campana

    PURPOSE Insulinomas are a rare type of neuroendocrine tumors, originating in the pancreas, difficult to diagnose and to treat. Due to its rarity, insulinomas are a not well-known pathological entity; thus, the diagnostic process is frequently a medical challenge with many possible differential diagnoses. The diagnostic process varies between non-invasive procedures, such as the fasting test or imaging techniques, and invasive ones. Insulinomas are rarely malignant, but the glycemic imbalance correlated with this tumor can frequently alter the quality of life of the patients and the consequent hypoglycemia can be extremely dangerous. Moreover, insulinomas can be associated with different genetic syndromes, such as Multiple Endocrine Neoplasia 1, accompanied by other specific symptoms. There are many different treatment strategies, depending on the need to control symptoms or control diseases progression, the only curative one being surgery. METHODS AND RESULTS We reviewed the evidences present in the literature on insulinomas and reported its main clinical characteristics and management strategies. CONCLUSION The aim of this review of the literature is to present the current knowledge on insulinomas, exploring the main clinical characteristics, the diagnostic tools, and the therapeutic strategies.

    更新日期:2020-01-21
  • Exon 3-deleted growth hormone receptor isoform is not related to worse bone mineral density or microarchitecture or to increased fracture risk in acromegaly.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-08-09
    J Pontes,M Madeira,C H A Lima,L L Ogino,F de Paula Paranhos Neto,L M C de Mendonça,M L F Farias,L Kasuki,M R Gadelha

    PURPOSE Acromegaly is a cause of secondary osteoporosis and is associated with increased risk of vertebral fractures (VFs). The influence of exon 3-deleted isoform of growth hormone receptor (d3-GHR) on bone microarchitecture has not been studied in acromegaly. AIM The aim of this study was to analyze the associations between d3-GHR isoform and bone mineral density (BMD), bone microarchitecture, and VFs in acromegaly patients. METHODS Consecutive acromegaly patients treated at a single reference center were included. BMD was analyzed using dual-energy X-ray absorptiometry (DXA) and bone microarchitecture was analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT). The presence of moderate to severe VFs was assessed by thoracic and lumbar X-ray. GHR genotyping was analyzed by PCR, and full-length isoform of GHR (fl-GHR) was represented by a 935-bp fragment and d3-GHR by a 532-bp fragment. RESULTS Eighty-nine patients were included [56 females; median age at diagnosis: 43 years (17-78)]. Disease was uncontrolled in 63% of patients. At least one d3-GHR allele was present in 60% of patients. Frequency of active disease (p = 0.276) and hypogonadism (p = 1.000) was not different between patients with fl-GHR and those with at least one d3-GHR. There was no difference in any DXA or HR-pQCT parameters between patients with fl-GHR and those with d3-GHR. Significant VFs were observed in 14% of patients, but there was no difference in frequency between patients with fl-GHR and those with at least one d3-GHR allele (p = 0.578). CONCLUSIONS Presence of d3-GHR was not associated with worse BMD or bone microarchitecture or with higher frequency of significant VFs.

    更新日期:2020-01-21
  • Treatment of Graves' hyperthyroidism with thionamides: a position paper on indications and safety in pregnancy.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    M Tonacchera,L Chiovato,L Bartalena,A F Cavaliere,P Vitti

    CONTEXT Graves' disease affects 3% of women and 0.5% of men in the general population. The first line treatment of Graves' hyperthyroidism is based on the administration of antithyroid drugs (ATD), propylthiouracil (PTU), methimazole (MMI) and carbimazole. A recent warning from the Italian Drug Agency (Agenzia Italiana del Farmaco AIFA) reported the risk of MMI-induced acute pancreatitis. In addition, AIFA highlighted the possible association of MMI treatment during the first trimester of pregnancy with congenital malformations, thus recommending the use of effective contraceptive methods in women of childbearing age treated with MMI. METHODS AND RESULTS Revision of literature reported less than ten cases of the alleged MMI pancreatitis, allowing the inclusion of MMI in class III drug regarding the relative risk for drug-induced pancreatitis. Data available on the effect of hyperthyroidism per se on the risk of fetal malformations, although scanty, are sufficient to recommend treatment with ATD of the hyperthyroid pregnant woman. Case reports and population studies either suggesting or not suggesting MMI-induced fetal malformations do not allow unquestionable conclusions on this matter. CONCLUSIONS This consensus by experts from Italian Endocrine and Gynecologic Scientific Societies has edited recommendations derived form the available data and published guidelines of International Scientific Societies.

    更新日期:2020-01-21
  • A broad range of symptoms in allgrove syndrome: single center experience in Southeast Anatolia.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    R Polat,A Ustyol,E Tuncez,T Guran

    BACKGROUND Allgrove syndrome (OMIM 231550) is a rare autosomal recessive disease characterized by non-CAH primary adrenal insufficiency (non-CAH PAI), alacrima, and achalasia. It is caused by mutations in the AAAS gene. The syndrome is also associated with variable progressive neurological impairment and dermatological abnormalities. METHODS AND RESULTS We diagnosed 23 patients from 14 families with Allgrove syndrome, based on the presence of at least two characteristic symptoms, usually adrenal insufficiency and alacrima, between 2008 and 2018. A previously described nonsense variant of AAAS was detected in 19 patients from 12 families at homozygous state. Another novel homozygous mutation (c.394-397delCTGT) in AAAS was detected in four patients from two families. Presenting symptoms were alacrima (23/23; 100%), adrenal insufficiency (18/23; 78%), achalasia (13/23; 57%), short stature/growth retardation (16/23; 70%), hyperreflexia (15/23; 65%), palmoplantar hyperkeratosis (13/23; 57%), hyperpigmentation of the skin (10/23; 43%), hypoglycemia-induced convulsion (7/23; 30%), swallowing difficulty and vomiting (6/23; 26%). Serum DHEAS concentrations were low in all patients (23/23; 100%). CONCLUSIONS Clinical symptoms vary even among patients carrying the same mutation. Triple A syndrome should be considered in the etiology of non-CAH PAI in Arab populations and in Southeast Turkey. Any child with non-CAH PAI should be evaluated for the presence of alacrima and/or achalasia or family history of alacrima and/or achalasia. Children with alacrima and/or achalasia should also be investigated for adrenal insufficiency. Definitive molecular diagnosis is essential for early diagnosis and management of adrenal insufficiency, neurological symptoms, and growth retardation in patients and early diagnosis of as yet asymptomatic cases in the family, together with genetic counseling.

    更新日期:2020-01-21
  • MicroRNAs expression in pituitary tumors: differences related to functional status, pathological features, and clinical behavior
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    T. M. Vicchio, F. Aliquò, R. M. Ruggeri, M. Ragonese, G. Giuffrida, O. R. Cotta, F. Spagnolo, M. L. Torre, A. Alibrandi, A. Asmundo, F. F. Angileri, F. Esposito, F. Polito, R. Oteri, M. H. Aguennouz, S. Cannavò, F. Ferraù

    Abstract Background MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at post-transcriptional level, having a role in many biological processes, such as control of cell proliferation, cell cycle, and cell death. Altered miRNA expression has been reported in many neoplasms, including pituitary adenomas (PAs). Purpose In this study, we aimed to evaluate the expression of 20 miRNAs involved in pathways relevant to pituitary pathophysiology, in PAs and normal pituitary tissue and to correlate their expression profile with clinical and pathological features. Methods Pituitary tumor samples were obtained during transphenoidal surgery from patients with non-functioning (NFPA, n = 12) and functioning (n = 11, 5 GH-, 3 ACTH-, 3 PRL-omas) PAs. The expression of selected miRNAs in PAs and in normal pituitary was analyzed by RT-qPCR. miRNAs expression was correlated with demographic, clinical, and neuroradiological data and with histopathological features including pituitary hormones immunostaining, Ki-67 proliferation index, and p53 immunohistochemistry evaluation. Results All evaluated miRNAs except miR-711 were expressed in both normal and tumor pituitary tissue. Seventeen miRNAs were significantly down-regulated in pituitary tumors compared to normal pituitary. miRNAs were differentially expressed in functioning PAs or in NFPAs, as in the latter group miR-149-3p (p = 0.036), miR-130a-3p (p = 0.014), and miR-370-3p (p = 0.026) were significantly under expressed as compared to functioning tumors. Point-biserial correlation analysis demonstrated a negative correlation between miR-26b-5p and Ki-67 (p = 0.031) and between miR-30a-5p and ‘atypical’ morphological features (p = 0.038) or cavernous sinus invasion (p = 0.049), while 508-5p was inversely correlated with clinical aggressiveness (p = 0.043). Conclusions In this study, we found a significant down-regulation of 17 miRNAs in PAs vs normal pituitary, with differential expression profile related to functional status and tumor aggressiveness.

    更新日期:2020-01-15
  • Effects of renin–angiotensin system blockers on renal and cardiovascular outcomes in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    X. Liu, L. Ma, Z. Li

    Abstract Purpose This study aimed to evaluate the effect f angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on renal or cardiovascular outcomes in patients with diabetic nephropathy (DN). Methods PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) evaluating the treatment effects of ACEI and ARB on renal or cardiovascular outcomes in patients with DN until August 2017. The outcomes included end-stage renal disease (ESRD), doubling of serum creatinine levels, all-cause mortality, major cardiovascular events (MACEs), myocardial infarction (MI), stroke, and cardiac death. Relative risks (RR) with 95% confidence intervals (CIs) were used for calculating the summary results using a random-effects model. Results Twenty-four RCTs including 57,818 patients with DN and 891 events of ESRD, 1050 doubling of serum creatinine concentration, 4352 all-cause mortality, 6342 MACEs, 1073 MI, 2900 stroke, and 1674 cardiac deaths were reported. Overall, the summary results suggested that in patients with DN, receiving ACEI did not have a significant effect on ESRD, doubling of serum creatinine levels, all-cause mortality, MI, stroke, and cardiac death, while ACEI significantly reduced the risk of total MACEs. Furthermore, ARB therapy was associated with a low risk of ESRD and doubling of serum creatinine levels, while it did not differ significantly on all-cause mortality, MACEs, MI, stroke, and cardiac death in patients with DN. Conclusions Patients with DN receiving ACEI had significantly reduced the risk of total MACEs, and ARB could reduce the incidence of ESRD and the doubling of serum creatinine levels.

    更新日期:2020-01-15
  • Two novel truncating variants of the AAAS gene causative of the triple A syndrome
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-14
    V. Vezzoli, P. Duminuco, G. Pogliaghi, M. Saccone, B. Cangiano, M. C. Rosatelli, A. Meloni, L. Persani, M. Bonomi

    The triple A syndrome (AAAS) is an inherited condition associated with mutations in the AAAS gene, which encodes a protein of 546 amino acids known as ALADIN (alacrima achalasia adrenal insufficiency neurologic disorder) whose function is not well understood. This protein belongs to the WD-repeat family of regulatory proteins and is located in the nuclear pore complexes. Only a few cohorts of AAAS patients have been reported and fully characterized. Thus, the objective of the present study was to report on a mini cohort of Italian AAAS patients and to get insights on their predisposing genetic defects.

    更新日期:2020-01-14
  • Tear inflammatory cytokines and ocular surface changes in patients with active thyroid eye disease treated with high-dose intravenous glucocorticoids
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-11
    N. Xu, Y. Cui, D. Fu, F. Sun

    To evaluate high-dose intravenous glucocorticoid treatment on tear inflammatory cytokines and ocular surface parameters in patients with active TED. Correlations between tear inflammatory cytokines and clinical parameters were also investigated.

    更新日期:2020-01-13
  • Clinical features may help to identify children and adolescents with greatest risk for thyroid nodules
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-11
    N. Allen, N. Desai, C. Song, J. Yu, U. Prasad, G. Francis

    Abstract Background Thyroid nodules (TN) are detected in a small number of asymptomatic children and adolescents but are more frequently malignant (22–26%) than in adults leading some clinicians to perform thyroid ultrasound (US) for all children with goiter or autoimmune thyroiditis (AIT). Our study was designed to determine if suspicious clinical features predict the presence of TN in children with goiter or AIT so that US could be performed on those at highest risk. Methods This was a retrospective review of 223 children and adolescents with goiter or AIT evaluated at a single institution. US was not performed on all patients. It is our practice to define glands that are large, firm, or nodular to palpation as “suspicious”. Suspicious glands were interrogated by US and if TN was confirmed, this was further evaluated by fine-needle aspiration followed by surgery if indicated. Results The median age was 12.9 years with 74.4% female. TN were confirmed by US in 16.6% of all patients but only 4.8% of those with AIT. By univariate analysis, TN were more common in those with family history of TN or differentiated thyroid carcinoma (DTC), thyroid asymmetry, and lower thyrotropin (TSH) levels. Differentiated thyroid carcinoma (DTC) was identified in 10.8% of TN and 1.8% of all patients. Firmness was significantly more common in patients with DTC (p = 0.0013). Conclusion TN were less common in those with AIT than reported in previous studies, suggesting that clinical features might fail to identify the majority of TN in patients with AIT. However, patients with asymmetric thyroid and a family history of TN or DTC have greatest risk for TN.

    更新日期:2020-01-13
  • Perimenopause, body fat, metabolism and menopausal symptoms in relation to serum markers of adiposity, inflammation and digestive metabolism
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-10
    G. Palla, C. Ramírez-Morán, M. M. Montt-Guevara, D. Salazar-Pousada, J. Shortrede, T. Simoncini, I. Grijalva-Grijalva, F. R. Pérez-López, P. Chedraui

    Perimenopausal women gain weight that may alter inflammatory status, endocrine equilibrium, and the intensity of vasomotor symptoms.

    更新日期:2020-01-11
  • Climacteric symptoms are related to thyroid status in euthyroid menopausal women.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-08-09
    R Slopien,M Owecki,A Slopien,G Bala,B Meczekalski

    BACKGROUND Climacteric symptoms are a variety of disturbing complaints occurring during menopausal transition, many of which may be influenced by hormonal abnormalities other than related to sex steroids. AIM OF THE STUDY In this study, we investigated the association between the intensity of climacteric symptoms measured with the Kupperman index and a thyroid status. MATERIAL AND METHODS We evaluated by measuring serum thyrotropin (TSH), and free thyroxine (fT4) 202 euthyroid women admitted to the Department of Gynecological Endocrinology, Poznan University of Medical Sciences because of climacteric symptoms. Patients were both in perimenopause (n = 74) and postmenopause (n = 128), with no history of thyroid disorders. RESULTS Results presented as the mean value and standard deviation were as follows: age 54.2 ± 4.9 years, BMI 26.8 ± 4.6 kg/m2, Kupperman index 26 ± 13.1 points, TSH 2.4 ± 2.6 mU/l, fT4 1.2 ± 0.37 ng/dl. We observed a negative correlation between fT4 and the time since the last menses (R = - 0.38; p = 0.02) as well as between serum TSH concentration and sweating (R = - 0.18; p = 0.03), general weakness (R = - 0.17; p = 0.03), and palpitation (R = - 0.18; p = 0.02) and a positive correlation between fT4 and nervousness (R = 0.34; p = 0.007) and palpitations (R = 0.25; p = 0.04). In the perimenopausal subgroup, there was a positive correlation between fT4 and general weakness (R = 0.42; p = 0.03), palpitations (R = 0.50; p = 0.009), and paresthesia (R = 0.46; p = 0.01). In the postmenopausal subgroup, there was a negative correlation between TSH and sweating (R = - 0.21; p = 0.03). CONCLUSIONS Menopausal symptoms are related to thyroid status in euthyroid menopausal women.

    更新日期:2020-01-09
  • Laser photocoagulation therapy for thyroid nodules: long-term outcome and predictors of efficacy.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    F Magri,S Chytiris,M Molteni,L Croce,F Coperchini,M Rotondi,R Fonte,L Chiovato

    PURPOSE The aim of the present study was to retrospectively evaluate the efficacy of interstitial laser photocoagulation (ILP) ablation of thyroid nodules during a 6-year follow-up period and to identify possible predictors of the final outcome. METHODS Forty-three outpatients (38 women) were assigned to ILP therapy. The study group included euthyroid patients with benign thyroid nodules. Thyroid size, nodule volume and features, and autoimmune test were collected at baseline. Patients underwent US control after the ILP procedure and 1 month, 6 months, 12 months later and then annually. RESULTS During the follow-up, two distinct groups of patients emerged: the responders (N = 33) and the non-responder (N = 10) ones to ILP. In the responder group, the nodule volume significantly decreased during the follow-up, but a trend toward a slight increase in nodule volume was recorded up to the end of follow-up. No significant decrease in nodule volume was observed in the non-responder group. Neither baseline clinical nor demographic features were significantly different between responders and non-responders groups. In the whole group of patients, the energy delivered per mL of nodule tissue was significantly correlated with the percent volume decrease at the end of follow-up. CONCLUSIONS Interstitial laser photocoagulation is a safe technique able to reduce byabout 50% the volume of benign thyroid nodules in the majority of treated patients. However, due to the great variability of results, an active follow-up is required. The only independent predictor of ILP outcome is the energy delivered per mL of nodule tissue.

    更新日期:2020-01-09
  • Non-specific rheumatic manifestations in patients with Hashimoto's thyroiditis: a pilot cross-sectional study.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    G Giuffrida,G Bagnato,A Campennì,S Giovinazzo,K P Keller,A Alibrandi,W N Roberts,F Trimarchi,R M Ruggeri

    PURPOSE Hashimoto's thyroiditis (HT) is often associated with rheumatic disorders (arthritis, etc.), but many HT patients report non-specific rheumatic signs and symptoms in the absence of clinically evident rheumatic diseases. Aim of this study was to evaluate the prevalence of non-specific rheumatic manifestations (RMs) in HT subjects without classified autoimmune comorbidities. METHODS 500 HT patients (467 F, 33 M; median age 41 years, range 14-69) and 310 age- and sex-matched controls, consecutively referred to the Endocrine Unit of Messina University Hospital, were evaluated for non-specific RMs. None took L-thyroxine. EXCLUSION CRITERIA autoimmune comorbidities, infectious, and/or inflammatory diseases, history of neoplasia, BMI > 30 kg/m2. RESULTS In our HT cohort, 100 patients (20%) complained of one or more RMs, vs 21 controls (6.8%; P < 0.001). There were minimal differences between the manifestations recorded in the two groups, the most common being polyarthralgias and myalgias/fibromyalgia, but non-specific RMs occurred threefold more in HT patients. Comparing HT patients with RMs (96 F and 4 M) with those affected by HT alone, female sex was prevalent (F:M ratio 24:1 vs 5:1) with higher age at diagnosis (median 43 vs 37 years; P < 0.001). HT patients with RMs (62%) were mostly euthyroid (median TSH 2.0 µIU/L) and only 7% overtly hypothyroid, discouraging a possible causal relationship between thyroid dysfunction per se and RMs. CONCLUSIONS A significant percentage of HT patients complains of non-specific rheumatic signs and symptoms, in the absence of other diagnosed systemic comorbidities and regardless of thyroid functional status, deserving careful evaluation and prolonged follow-up.

    更新日期:2020-01-09
  • Features and outcome of differentiated thyroid carcinoma associated with Graves' disease: results of a large, retrospective, multicenter study.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-07-22
    P Premoli,M L Tanda,E Piantanida,G Veronesi,D Gallo,E Masiello,S Rosetti,C Cusini,F Boi,J Bulla,R Rodia,S Mariotti,V Capelli,M Rotondi,F Magri,L Chiovato,R Rocchi,M C Campopiano,R Elisei,P Vitti,F Barbato,T Pilli,M G Castagna,F Pacini,L Bartalena

    BACKGROUND Whether differentiated thyroid cancer (DTC) occurring concomitantly with Graves' disease (GD) is more aggressive and bound to a less favorable outcome is controversial. OBJECTIVE Aim of this multicenter retrospective study was to compare baseline features and outcome of DTC patients with GD (DTC/GD+) or without GD (DTC/GD-). PATIENTS Enrolled in this study were 579 patients referred to five endocrine units (Cagliari, Pavia, Pisa, Siena, and Varese) between 2005 and 2014: 193 patients had DTC/GD+ , 386 DTC/GD-. Patients were matched for age, gender and tumor size. They underwent surgery because of malignancy, large goiter size, or relapse of hyperthyroidism in GD. RESULTS Baseline DTC features (histology, lymph node metastases, extrathyroidal extension) did not differ in the two groups, except for multifocality which was significantly more frequent in DTC/GD+ (27.5% vs. 7.5%, p < 0.0001). At the end of follow-up (median 7.5 years), 86% of DTC/GD+ and 89.6% DTC/GD- patients were free of disease. Patients with persistent or recurrent disease (PRD) had "biochemical disease" in the majority of cases. Microcarcinomas were more frequent in the DTC/GD+ group (60% vs. 37%, p < 0.0001) and had an excellent outcome, with no difference in PRD between groups. However, in carcinomas ≥ 1 cm, PRD was significantly more common in DTC/GD+ (24.4% vs. 11.5%; p = 0.005). In the whole group, univariate and multivariate analyses showed that GD+ , lymph node involvement, extrathyroidal invasion, multifocality and tall cell histotype were associated with a worse outcome. Female gender and microcarcinomas were favorable features. No association was found between baseline TSH-receptor antibody levels and outcome. Graves' orbitopathy (GO) seemed to be associated with a better outcome of DTC, possibly because patients with GO may early undergo surgery for hyperthyroidism. CONCLUSIONS GD may be associated with a worse outcome of coexisting DTC only if cancer is ≥ 1 cm, whereas clinical outcome of microcarcinomas is not related to the presence/absence of GD.

    更新日期:2020-01-09
  • No effect of acidification or freezing on urinary metanephrine levels.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    L C Pinto,C K Kramer,J L Camargo,L H Canani,J L Gross,C B Leitão

    BACKGROUND Urinary metanephrine is a reliable method to estimate catecholamine secretion. Traditionally, urinary metanephrines are collected into chilled containers containing hydrochloric acid (HCl) and most laboratories freeze urinary samples before analysis. It is uncertain if these pre-analytic procedures alter metanephrine values. AIM To evaluate if acidifying and freezing urine samples affect the accuracy of urinary metanephrine measurements. METHODS Random urine samples from healthy individuals were collected. Urine samples were distributed into two containers: with HCl 50% homogenized with urine to obtain pH < 2, and without HCl. Each container was divided again into aliquots for immediate measurement or freezing. One aliquot with acid (group 1) and another without acid (group 2) were sent immediately to the laboratory for testing (HPLC), while the other two aliquots, one with acid (group 3) and another without it (group 4) were frozen for 3 months at - 20 °C. Bland-Altman's test was used to analyze inter-assay agreement between measurements. RESULTS A total of 15 individuals were included (mean age 27.5 ± 5.9 years, 8 male and 14 white). No difference was observed on mean urinary metanephrine/creatinine ratio between groups: group 1: 0.23 ± 0.11, group 2: 0.22 ± 0.07, group 3: 0.25 ± 0.13, group 4: 0.25 ± 0.15 mg/g creatinine; P > 0.05 for all the comparisons). Bland-Altman's analysis showed agreement between the standard method (group 1) and the experimental method (group 4). CONCLUSION Measurement of urinary metanephrines by HPLC method is not influenced by sample acidification nor freezing at - 20 °C for 3 months.

    更新日期:2020-01-09
  • Anti-gastric parietal cell antibodies for autoimmune gastritis screening in juvenile autoimmune thyroid disease.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    V Calcaterra,C Montalbano,E Miceli,O Luinetti,R Albertini,F Vinci,C Regalbuto,D Larizza

    OBJECTIVE Patients with autoimmune thyroid disease (ATD) have a higher prevalence of autoimmune gastritis (AIG) compared with the general population. The association between ATD and AIG is poorly characterized in the pediatric age. We reviewed the prevalence of anti-gastric parietal cell antibodies (PCA) in young patients with ATD to evaluate its usefulness as a marker for AIG screening. METHODS We evaluated 220 children and adolescents (11.28 ± 6.37 years) with ATD (186 with autoimmune thyroiditis (AT) and 34 with Graves' disease (GD). At ATD diagnosis and annually thereafter, blood counts and PCA levels were measured. In patients positive for PCA, plasma gastrin, chromogranin A, vitamin B12, iron and ferritin levels and H. pylori antigen were measured. PCA-positive patients > 18 years were invited to undergo a gastroscopic exam. RESULTS PCA positivity was detected in ten (4.5%) subjects (5F/5M; 12.6 ± 3.4 years). The prevalence of PCA positivity was not significantly different in the comparison of GD and AT patients (p = 0.9). PCA positivity was detected after 2.7 ± 2.7 years of follow-up in AT and 4.4 ± 4.0 years in GD (p = 0.4). Autoantibody positivity was more prevalent in female patients, in both AT and GD (p = 0.02 and p = 0.03, respectively). At detection of PCA positivity, five out of ten PCA-positive patients had iron deficiency, four vitamin B12 deficiency, two anemia, three hypergastrinemia and two elevated chromogranin values. Two patients had H. pylori infection. Gastroscopy was performed in the five ATD patients and in all patients, AIG was confirmed. CONCLUSION In the juvenile population, ATD and AIG may also be associated. PCA screening is useful to detect subjects at risk for this condition. Due to the longer life expectancy of the pediatric population and considering the relatively high risk of malignant transformation, early surveillance monitoring is mandatory for children and adolescents with ATD.

    更新日期:2020-01-09
  • Wrist circumference is a biomarker of adipose tissue dysfunction and cardiovascular risk in children with obesity.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    C Luordi,E Maddaloni,C Bizzarri,S Pedicelli,S Zampetti,L D'Onofrio,C Moretti,M Cappa,R Buzzetti

    PURPOSE To evaluate the relationship between wrist circumference, markers of adipose dysfunction, and cardiovascular risk in youths with obesity. METHODS In this cross-sectional study, we measured body mass composition by dual-energy X-ray absorptiometry, wrist circumference, waist-to-height ratio, fasting blood insulin, glucose, lipid profile, adiponectin, and leptin in 280 children with overweight/obesity and without diabetes (age: 7-18 years). Cardiovascular risk was estimated by "metabolic syndrome score" (MetS score). RESULTS Study participants had median [25th-75th percentile] wrist circumference of 17.5 [16.7-18.5] cm and waist-to-height ratio of 0.62 [0.59-0.67]. Lower adiponectin-leptin ratio was found among subjects in the upper 50th percentiles of wrist circumference [0.17 (0.09-0.36) vs. 0.38 (0.16-0.79); p < 0.001]. Wrist circumference was independently associated with MetS score (r = 0.5 p < 0.001). Among MetS score components, an independent association between wrist circumference HDLc, triglycerides, and systolic blood pressure was found (r = - 0.253 p < 0.001; r =+ 0.204 p < 0.001; r = + 0.403 p = < 0.001, respectively). The coefficient of determination for MetS score was nominally higher when considering wrist circumference as independent variable (Adj-R2 = 0.30) then when considering body mass index SD (Adj-R2 = 0.28), waist-to-height ratio (Adj-R2 = 0.26) or truncal fat percentage (Adj-R2 = 0.01). The addition of wrist circumference in age and gender adjusted models, accounting to any other anthropometric parameters, resulted in a significant improvement of the Adj-R2 (p < 0.001 for all). CONCLUSIONS Our study shows that wrist circumference independently relates to adiponectin-leptin ratio and to the prediction of cardiovascular risk, suggesting it as an efficient and adjunctive anthropometric marker of cardiometabolic risk in children with obesity.

    更新日期:2020-01-09
  • Metformin as a protective agent against natural or chemical toxicities: a comprehensive review on drug repositioning.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    S E Meshkani,D Mahdian,K Abbaszadeh-Goudarzi,M Abroudi,G Dadashizadeh,J-D Lalau,M E De Broe,H Hosseinzadeh

    BACKGROUND Metformin is the first prescribed drug for hyperglycemia in type 2 diabetes mellitus. Mainly by activating AMPK pathway, this drug exerts various functions that among them protective effects are of the interest. PURPOSE Herein, we aimed to gather data about the protective impacts of metformin against various natural or chemical toxicities. RESULTS An extensive search among PubMed, Scopus, and Google Scholar was conducted by keywords related to protection, toxicity, natural and chemical toxins and, metformin. Our literature review showed metformin alongside its anti-hyperglycemic effect has a wide range of anti-toxic effects against anti-tumour and routine drugs, natural and chemical toxins, herbicides and, heavy metals. CONCLUSION It is evident that metformin is a potent drug against the toxicity of a broad spectrum of natural, chemical toxic agents which is proved by a vast number of studies. Metformin mainly through AMPK axis can protect different organs against toxicities. Moreover, metformin preserves DNA integrity and can be an option for adjuvant therapy to ameliorate side effect of other therapeutics.

    更新日期:2020-01-09
  • The treatment with pasireotide in Cushing's disease: effect of long-term treatment on clinical picture and metabolic profile and management of adverse events in the experience of a single center.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    C Simeoli,R Ferrigno,M C De Martino,D Iacuaniello,F Papa,D Angellotti,C Pivonello,R Patalano,M Negri,A Colao,R Pivonello

    PURPOSES Pasireotide is the first medical therapy officially approved for adult patients with Cushing's disease (CD) experiencing failure of pituitary surgery or not candidates for surgery. The current study aimed at investigating pasireotide effects on clinical picture and metabolic profile in patients enrolled in the phase III CSOM230B2305 trial at Naples center. In addition, the current study focused on safety issues encountered during the study, detailing the management of the different adverse events associated with the treatment with pasireotide in Naples center. METHODS Fourteen patients entered the study; eight patients, receiving pasireotide for at least 6 months, were considered for the efficacy analysis, whereas the entire cohort of 14 patients was considered for the safety analysis. RESULTS Full or partial disease control was obtained in 85.7% of patients, according to a "per-protocol" methodology analysis, and in 42.9% of patients, according to an "intention-to-treat" methodology analysis, after 12 months of treatment. A relevant improvement in clinical signs and symptoms, mainly in facial rubor, supraclavicular fat pad, bruising, hirsutism, and muscle strength was observed; body weight, body mass index, and waist circumference significantly reduced, and a slight non-significant reduction was observed in the prevalence of visceral obesity, hypercholesterolemia, and hypertriglyceridemia. Deterioration of glucose metabolism represented the most common adverse event, occurring in 71.4% of patients, and requiring a dietary regimen as first step, metformin therapy and/or long-acting insulin as second step, and short-acting insulin, as third step; no patients discontinued treatment for hyperglycaemia. Additional adverse events of interest were nausea (21.4%), and vomiting (14.3%), spontaneously resolved in few weeks or some months, except in one patient unsuccessfully treated with metoclopramide and ondansetron, and diarrhoea (14.3%), improved with loperamide treatment. Millimetric gallstones and biliary sludge (7.1%) were managed with ursodeoxycholic acid, inducing lithiasis and biliary sludge resolution, whereas hypocortisolism-related adverse events (7.1%) were resolved with a reduction in the pasireotide dose. CONCLUSIONS The current study on a limited series of patients contributes to confirm that pasireotide may be considered a valid option for treatment of patients with CD, although it requires an appropriate management of adverse events, especially hyperglycaemia.

    更新日期:2020-01-09
  • Association between iodine intake and thyroid autoantibodies: a cross-sectional study of 7073 early pregnant women in an iodine-adequate region.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    J Sun,D Teng,C Li,S Peng,J Mao,W Wang,X Xie,C Fan,C Li,T Meng,S Zhang,J Du,Z Gao,Z Shan,W Teng

    PURPOSE The association between iodine intake and thyroid autoimmunity has been debated, especially in pregnant women. This study aimed to investigate thyroid autoantibodies and their association with iodine intake and hypothyroidism in early pregnancy. METHODS 7073 early pregnant women from an iodine-sufficient region participated in this study. Urinary iodine concentrations (UICs) were measured using an ammonium persulfate method. Serum thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and Tg were determined using an electrochemiluminescence immunoassay. RESULTS Iodine deficiency (UIC < 100 μg/L) was associated with higher risks of TPOAb positivity [adjusted odds ratio (aOR) = 1.64, 95% confidence interval [CI] (1.29-2.08)] and TgAb positivity [aOR = 1.44, 95% CI (1.16-1.80)]. Women with isolated TPOAb positivity, isolated TgAb positivity, or both TPOAb and TgAb positivity had a 14.64-fold, 7.83-fold, and 44.69-fold increased risk of overt hypothyroidism, and a 4.36-fold, 2.86-fold, and 6.26-fold increased risk of subclinical hypothyroidism, respectively. Moreover, the risks of overt and subclinical hypothyroidism in women with a high TPOAb titer were 16.99 and 4.80 times that in TPOAb-negative women, respectively. The risk of overt hypothyroidism in women with a high TgAb titer was 6.97 times that in TgAb-negative women. CONCLUSIONS Our work demonstrates that iodine deficiency during early pregnancy is an independent risk factor for both TPOAb positivity and TgAb positivity. Furthermore, positivity for both autoantibodies and a high thyroid autoantibody titer are associated with significantly higher risks of overt and subclinical hypothyroidism.

    更新日期:2020-01-09
  • Will the shepherd be able to play the alpine horn with that huge goiter (XVI century)?
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-06
    R. Dionigi, D. Zhang, G. Dionigi

    There are many of the representations in iconography of individuals with goiters reported in the literature.

    更新日期:2020-01-06
  • Association between vitamin D deficiency and common variants of Vitamin D binding protein gene among Mexican Mestizo and indigenous postmenopausal women
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-06
    B. Rivera-Paredez, A. Hidalgo-Bravo, A. de la Cruz-Montoya, M. M. Martínez-Aguilar, E. G. Ramírez-Salazar, M. Flores, A. D. Quezada-Sánchez, P. Ramírez-Palacios, M. Cid, A. Martínez-Hernández, L. Orozco, E. Denova-Gutiérrez, J. Salmerón, R. Velázquez-Cruz

    Abstract Purpose Vitamin D deficiency (VDD) and polymorphisms in the group-specific component (GC) gene are known to be associated in different populations. However, the effects of such genetic variants may vary across different populations. Thus, the objective of this study was to estimate the association between Vitamin D-Binding Protein (VDBP) haplotypes and VDD in mestizo postmenopausal women and Mexican Amerindian ethnic groups. Methods This was a cross-sectional study of 726 postmenopausal Mexican women from the Health Workers Cohort Study (HWCS) and 166 postmenopausal women from the Metabolic Analysis in an Indigenous Sample (MAIS) cohort in Mexico. GC polymorphisms (rs7045 and rs4588) were analyzed by TaqMan probes. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured by Chemiluminescent Microparticle Immuno Assay. Results The prevalence of VDD serum 25(OH)D < 20 ng/mL was 43.7% in mestizo women and 44.6% in indigenous women. In HWCS, the single nucleotide polymorphisms (SNPs) rs7041 and rs4588 were associated with VDD. In addition, women from the HWCS, carrying the haplotypes GC2/2 and GC1f/2 had higher odds of VDD (OR = 2.83, 95% CI 1.14, 7.02; and OR = 2.30, 95% CI 1.40, 3.78, respectively) compared to women with haplotype 1f/1 s. These associations were not statistically significant in the MAIS cohort. Conclusions Our results show genetic association of the analyzed SNPs and related haplotypes, on the GC gene, with VDD in mestizo Mexican postmenopausal women. Moreover, a high prevalence of VDD with high genetic variability within the country was observed. Our results support the need for national policies for preventing VDD.

    更新日期:2020-01-06
  • Long-term ultrasound follow-up of intrathyroidal ectopic thymus in children
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-04
    D. Januś, A. Kalicka-Kasperczyk, M. Wójcik, G. Drabik, J. B. Starzyk

    Abstract Objective To present the sonographic follow-up of intrathyroidal ectopic thymus (IET) in children and adolescent patients. Patients Out of the 507 children referred to FNAB between 2006 and 2018, 30 (5.9%) pediatric patients (10 females), mean age 5.7 years (1.2–13.8, median 4.9 years) were diagnosed with IET. Methods A retrospective analysis of medical files of patients diagnosed with IET between 2006 and 2018. Assessed data included ultrasound characterisation, elastographic strain ratio (SR) results and hormonal evaluation. Results Analysis of thyroid US scans revealed that the mean age at the first thyroid ultrasound was 5.7 (1.2–13.8, median 4.9) years, and at the last US 10.7 (3.7–18, median 10.5) years. The mean time of the IET observation was 59.6 (2–148, median 53.5) months. On US, IET was hypoechoic with multiple linear and punctate echoes, hypovascular, fusiform on longitudinal plane and round or polygonal on an axial plane, more common in the right thyroid lobe (66.7%) and located in the posterior part of the lobes (54.5%), bilateral in two patients and multifocal in one patient. SR of IET was similar to the surrounding normal thyroid tissue. Complete regression of IET was observed in 12/30 patients after a mean time of 81.7 months (median 76.5), at the mean age of 13.7 (9.2–18, median 13.9) years. FNAB was performed in 10/30 and a hemithyroidectomy in 1/30 IET patients. In the FNAB (+) group, patients were younger (5.08 vs 6.08 years) and lesions were larger (0.12 ml vs 0.05 ml) than in the FNAB (−) group. All patients with IET were euthyroid with negative TPOAb and TgAb levels. Conclusion The reproducibility of unique ultrasound features of IETs allows for safe long-term follow-up of these benign lesions in the majority of pediatric patients: not only monitoring the regression of IET but also screening towards the rare occurrence of a tumor arising from the IET.

    更新日期:2020-01-04
  • Alternate-day calcium dosing may be an effective treatment option for chronic hypoparathyroidism
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-03
    T. Akkan, M. Dagdeviren, A. O. Koca, D. T. Ertugrul, M. Altay

    Conventional treatment of chronic hypoparathyroidism consists of oral calcium supplements and active vitamin D analogs; however, some patients are unable to meet treatment goals despite the high dosage of oral calcium supplementation. We aimed to investigate the effectiveness of alternate-day oral calcium intake in patients with uncontrolled chronic hypoparathyroidism.

    更新日期:2020-01-04
  • Does autoimmune hypothyroidism increase the risk of neurovascular complications in type 1 diabetes?
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-03
    A. Rogowicz-Frontczak, B. Falkowski, A. Grzelka-Wozniak, A. Uruska, A. Araszkiewicz, D. Zozulinska-Ziolkiewicz

    Abstract Background Type 1 diabetes (T1DM) often coexists with other autoimmune diseases, most commonly with hypothyroidism. To date, the influence of coexisting autoimmune hypothyroidism (AHT) on the course of chronic neurovascular complications of autoimmune diabetes has not been established. The aim of the study was to assess the relationship between AHT and the occurrence of chronic T1DM complications. Methods The study group comprised 332 European Caucasian participants with T1DM [165 (49.7%) men]. AHT was recognized in subclinical and overt hypothyroidism and confirmed by the presence of anti-thyroid autoantibodies: anti-peroxidase (ATPO) and/or anti-thyroglobulin (ATg) and ultrasonography (hypoechogenicity, parenchymal heterogeneity, lymph nodes assessment). Results In the analyzed group, 48.5% of patients were diagnosed with at least one neurovascular complication. At the time of enrollment, 16.3% of participants were diagnosed with AHT. Patients with AHT, compared to those without AHT, were characterized by a higher prevalence of neurovascular complications (64.8 vs. 45.3%; P = 0.009) and retinopathy (55.6 vs. 38.9%; P = 0.02). There were significant differences between groups with and without neurovascular complications, with regard to classic risk factors for chronic diabetes complications: age, T1DM duration, SBP, DBP, HbA1c, TG, eGFR and hypertension prevalence. In the multivariate logistic regression analysis, AHT was an independent predictor of neurovascular complications after adjusting for age, DBP, HbA1c and TG (odds ratio, 2.40; 95% confidence interval, 1.17–4.92; P = 0.02). Conclusions AHT coexisting with T1DM was associated with a higher incidence of neurovascular complications.

    更新日期:2020-01-04
  • Is Somatostatin Receptor and Dopamine Receptor profiling useful in the management of silent somatotroph tumors?
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-02
    S. Martínez-López, A. García-Martínez, M. E. Torregrosa-Quesada, B. López-Muñoz, R. Cámara, C. Fajardo, C. Lamas, A. Picó

    Abstract Silent somatotroph tumors (sSTs) are pituitary neuroendocrine tumors (PitNETs) which do not give rise to the clinical syndrome of acromegaly. Differently to their functioning counterparts, the adjuvant medical treatment with somatostatin analogues (SSAs) or dopamine receptors agonists (DAs) has been scarcely addressed in these tumors. As preliminary results of an ongoing research on silencing mechanisms involved in the pathogenesis of sSTs, we have characterized by qRT-PCR the expression of SSTRs and DRDs in a large series of 18 silent and 68 functioning STs. Although the expression of SSTR2 and SSTR5 was lower in sSTs than in functioning ones, we found a negative correlation between SSTR2 and the tumor size of the sSTs. Additionally, levels of expression of DRD2 were similar between the two subtypes suggesting a possible basis for the treatment of these tumors with SSAs and DAs.

    更新日期:2020-01-04
  • Thyroid hormones T3 and T4 regulate human luteinized granulosa cells, counteracting apoptosis and promoting cell survival
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2020-01-01
    V. Di Paolo, C. Mangialardo, C. Zacà, M. Barberi, E. Sereni, A. Borini, M. Centanni, G. Coticchio, C. Verga-Falzacappa, R. Canipari

    Abstract Purpose Fine and balanced regulation of cell proliferation and apoptosis are key to achieve ovarian follicle development from the primordial to the preovulatory stage and therefore assure female reproductive function. While gonadotropins are the major and most recognized regulators of follicle cell growth and function, other factors, both systemic and local, play equally important roles. This work is aimed at evaluating the effects of thyroid hormones (THs) on human granulosa luteinized (hGL) viability. Methods Human GL cells derived from assisted reproduction treatments were exposed to T3 or T4. Cell viability was evaluated by MTT assay. Apoptosis was evaluated by the TUNEL assay and active caspase-3 staining. StAR, CYP19A1,Caspase-3, P53 and BAX mRNA were evaluated by real-time PCR. LC3-I/-II, AKT and pAKT were evaluated by western blot. Results T3 and T4 promoted cell viability in a dose-dependent modality and modulate StAR and CYP19A1 expression. T3 and to a lesser extent T4 mitigated cell death induced by serum starvation by inhibition of caspase-3 activity and expression of P53 and BAX; and attenuate cell death experimentally induced by C2-ceramide. Cell death derived from starvation appeared to be involved in autophagic processes, as the levels of autophagic markers (LC3-II/LC3-I ratio) decreased when starved cells were exposed to T3 and T4. This effect was associated with an increase in pAkt levels. Conclusion From the present study, THs emerge as potent anti-apoptotic agents in hGL cells. This effect is achieved by inhibiting the apoptosis signalling pathway of BAX and caspase-3, while maintaining active the PI3K/AKT pathway.

    更新日期:2020-01-04
  • Hypercalciuria: its value as a predictive risk factor for nephrolithiasis in asymptomatic primary hyperparathyroidism?
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-23
    F. Saponaro, F. Cetani, L. Mazoni, M. Apicella, M. Di Giulio, F. Carlucci, M. Scalese, E. Pardi, S. Borsari, J. P. Bilezikian, C. Marcocci

    Abstract Context The latest guidelines of the 4th International Workshop on Asymptomatic Primary Hyperparathyroidism (aPHPT) reintroduced hypercalciuria (i.e. urinary calcium > 400 mg/day) as criterion for surgery. However, the value of hypercalciuria as a predictor of nephrolithiasis and the correct cut-off values still need to be confirmed. Objective To evaluate the prevalence of silent kidney stones in a large series of patients with aPHPT and the sensibility, specificity and predictive value of different cut-off values of hypercalciuria in identifying patients with nephrolithiasis. Design One hundred seventy-six consecutive patients with aPHPT were evaluated at our Institution by serum and urinary parameters and kidney ultrasound. Results Silent nephrolithiasis was found in 38 (21.6%) patients. In the univariate and multivariate model, hypercalciuria was a predictor of nephrolithiasis using the criterion of 400 mg/24 h [(OR 2.30, (1.11–4.82) P = 0.025], 4 mg/kg/bw [OR 2.65, (1.14–6.25) P = 0.023], gender criterion [OR 2.79, (1.15–6.79) P = 0.023] and the cut-off value derived from the ROC analysis [(> 231 mg/24 h) OR 5.02 (1.68–14.97) P = 0.004]. Despite these several predictive criteria, however, hypercalciuria had a low positive predictive value (PPV), ranging from 27.4 to 32.7%. Conclusions Hypercalciuria is a predictor of nephrolithiasis, but its PPV is low.

    更新日期:2020-01-04
  • FGF23-related hypophosphatemia in patients with low bone mineral density and fragility fractures: challenges in diagnosis and management
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-20
    R. Indirli, G. Guabello, M. Longhi, S. Niada, K. Maruca, S. Mora, M. Maggioni, S. Corbetta

    Hypophosphatemia (HP) can be observed in patients evaluated for skeletal fragility. We investigated prevalence of HP among outpatients referred for low bone density or fragility fractures, HP-associated clinical and biochemical features and outcomes of recommended diagnostic algorithm in our cohort.

    更新日期:2020-01-04
  • Association of thyroid cancer risk with plasma 25-hydroxyvitamin D and vitamin D binding protein: a case–control study in China
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-20
    M.-J. Hu, Q.-S. Niu, H.-B. Wu, X.-L. Lu, L. Wang, X.-R. Tong, Fen Huang

    Abstract Purpose To investigate the association of thyroid cancer (TC) with 25-hydroxyvitamin D [25(OH)D] and vitamin D binding protein (DBP) and examine whether there was an interaction between 25(OH)D and DBP in relation to TC risk. Methods A matched case–control study based on multiple hospitals included 506 pairs of cases with newly diagnosed TC and controls. All subjects were divided into the quartiles according to the distribution of 25(OH)D and DBP in controls. Odds ratio (OR) and 95% confidence intervals (CIs) for the association of TC with 25(OH)D and DBP were estimated by conditional logistic regression. Results Comparing the highest to lowest quartiles, a decreased TC risk was respectively associated with plasma 25(OH)D (OR 0.63, 95% CI 0.40–1.00, P-trend = 0.046) and DBP (OR 0.49, 95% CI 0.32–0.77, P-trend = 0.001). However, the association between DBP and TC might be modified by 25(OH)D (P-interaction = 0.014) and physical activity (P-interaction = 0.017). Compared to participants with 25(OH)D and DBP concentrations respectively below medians, those with both concentrations above medians had a lower risk of TC (OR 0.56, 95% CI 0.39–0.82). In stratified analysis based on clinical characteristics of tumor, significantly negative association between 25(OH)D, and DBP and TC were observed among the cases with early stage of tumor progression. Conclusions This study suggested that 25(OH)D and DBP had protective effects against TC. But the negative association between TC and DBP might be modified by 25(OH)D and physical activity.

    更新日期:2020-01-04
  • Development of a novel score to predict probability of growth without growth hormone after resection of paediatric craniopharyngiomas: relative to tumour growth pattern
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-18
    J. X. Peng, L. Yang, G. L. Huang, Y. Liu, S. C. Zhang, J. Pan, S. T. Qi

    Some patients with paediatric craniopharyngiomas (PCs) showed normal growth despite growth hormone deficiency, which is known as growth without GH (GWGH); however, its mechanism remains unclear. We aimed to develop a novel clinical score to predict the probability of GWGH in PCs.

    更新日期:2020-01-04
  • Molecular markers for the classification of cytologically indeterminate thyroid nodules
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-18
    M. Muzza, C. Colombo, G. Pogliaghi, O. Karapanou, L. Fugazzola

    Abstract Background The diagnosis of indeterminate lesions of the thyroid is a challenge in cytopathology practice. Indeed, up to 30% of cases lack the morphological features needed to provide definitive classification. Molecular tests have been developed to assist in the diagnosis of these indeterminate cases. The first studies dealing with the preoperative molecular evaluation of FNA samples focused on the analysis of BRAFV600E or on the combined evaluation of two or three genetic alterations. The sensitivity of molecular testing was then improved through the introduction of gene panels, which became available for clinical use in the late 2000s. Two different categories of molecular tests have been developed, the ‘rule-out’ methods, which aim to reduce the avoidable treatment of benign nodules, and the ‘rule-in’ tests that have the purpose to optimize surgical management. The genetic evaluation of indeterminate thyroid nodules is predicted to improve patient care, particularly if molecular tests are used appropriately and with the awareness of their advantages and weaknesses. The main disadvantage of these tests is the cost, which makes them rarely used in Europe. To overcome this limitation, customized panels have been set up, which are able to detect the most frequent genetic alterations of thyroid cancer. Conclusions In the present review, the most recent available versions of commercial molecular tests and of custom, non-commercial panels are described. Their characteristics and accuracy in the differential diagnosis of indeterminate nodules, namely Bethesda classes III (Atypical follicular lesion of undetermined significance, AUS/FLUS) and IV (Suspicious for follicular neoplasm, FN/SFN) are fully analyzed and discussed.

    更新日期:2020-01-04
  • Non-invasive and real-time proliferative activity estimation based on a quantitative radiomics approach for patients with acromegaly: a multicenter study
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-17
    Y. Fan, Y. Chai, K. Li, H. Fang, A. Mou, S. Feng, M. Feng, R. Wang

    Abstract Background Proliferative activity prediction is important for determining individual treatment strategies for patients with acromegaly, and tumor proliferative activity is usually measured by the expression of Ki-67. Objective This study aimed to assess the value of a magnetic resonance imaging (MRI)-based radiomics approach in predicting the Ki-67 index of acromegaly patients. Methods A total of 138 patients with acromegaly were retrospectively reviewed and randomly assigned to primary and validation cohorts. Radiomics features were extracted from MR images, and then the elastic net and recursive feature elimination algorithms were applied to determine critical radiomics features for constructing a radiomics signature. Subsequently, multivariable logistic regression analysis was used to select the most informative clinical features, and a radiomics nomogram incorporating a radiomics signature and selected clinical features was constructed for individual predictions. Twenty-five acromegaly patients were enrolled for multicenter model validation. Results Seventeen radiomics features were selected to construct a radiomics signature that achieved an area under the curve (AUC) value of 0.96 and 0.89 in the primary cohort and the validation cohort, respectively. A radiomics nomogram that incorporated the radiomics signature and eight selected clinical features was constructed and showed good discrimination and calibration, with an AUC of 0.94 in the primary cohort and 0.91 in the validation cohort. The radiomics signature in the multicenter validation achieved an accuracy of 88.2%. The analysis of the decision curve showed that the radiomics signature and radiomics nomogram were clinically useful for patients with acromegaly. Conclusions The radiomics signature developed in this study could aid neurosurgeons in predicting the Ki-67 index of patients with acromegaly and could contribute to non-invasive measurement of proliferative activity, affecting individual treatment strategies.

    更新日期:2020-01-04
  • Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-16
    N. Schiuma, A. Costantino, T. Bartolotti, M. Dattilo, V. Bini, M. C. Aglietti, M. Renga, A. Favilli, A. Falorni, S. Gerli

    Fasting blood homocysteine is increased in PCOS women and is involved in several of its co-morbidities including cardiovascular disease and infertility. Corrective interventions based on the administration of supra-physiologic doses of folic acid work to a low extent. We aimed to test an alternative approach.

    更新日期:2020-01-04
  • Kisspeptin and neurokinin B analogs use in gynecological endocrinology: where do we stand?
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-14
    A. Szeliga, A. Podfigurna, G. Bala, B. Meczekalski

    Recent studies have found that kisspeptin/neurokinin B/dynorphin neurons (KNDy neurons) in the infundibular nucleus play a crucial role in the reproductive axis. Analogs, both agonists and antagonists, of kisspeptin and neurokinin B (NKB) are particularly important in explaining the physiological role of KNDy in the reproductive axis in animals. The use of kisspeptin and NKB analogs has helped elucidate the regulators of the hypothalamic reproductive axis.

    更新日期:2020-01-04
  • Systemic safety analysis of mycophenolate in Graves’ orbitopathy
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-13
    A. C. H. Lee, M. Riedl, L. Frommer, T. Diana, G. J. Kahaly

    The dual antiproliferative mechanism of mycophenolate appears to be beneficial in Graves’ orbitopathy (GO).

    更新日期:2020-01-04
  • XRCC1 Arg194Trp polymorphism and thyroid cancer
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-09
    S.-Y. Liu, W. Xue

    Previously published data on the association between the XRCC1 Arg194Trp polymorphism and thyroid cancer (TC) remain controversial.

    更新日期:2020-01-04
  • Primary sellar melanocytoma: pathological, clinical and treatment review
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-03
    L. Albano, M. Losa, L. R. Barzaghi, G. Spatola, P. Panni, M. R. Terreni, P. Mortini

    Sellar melanocytomas represent a small subgroup of primary melanocytic tumors. They arise from melanocytes located in the meningeal lining of the sellar floor or in the diaphragma sellae and this location is very uncommon. Usually, sellar melanocytomas are benign and slow-growing tumors with a high likelihood of recurrence.

    更新日期:2020-01-04
  • “The giant Hans Kraus” (1553): a Renaissance acromegaly by anonymous painter
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-05-20
    L. Cambioli, M. A. Riva

    The Wunderkammer of Schloss Ambras in Innsbruck was one of the first cabinets of curiosities, created in the sixteenth century. Among the many curiosities, the cabinet includes an anonymous Renaissance painting called “Der Riese Hans Kraus” (The giant Hans Kraus). The details suggest us that it could be a representation of an individual affected by acromegaly.

    更新日期:2020-01-04
  • Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-05-24
    R. Palui, J. Sahoo, S. Kamalanathan, S. S. Kar, K. Sridharan, H. Durgia, H. Raj, M. Patil

    Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH).

    更新日期:2020-01-04
  • Serum levels of adipokines in gestational diabetes: a systematic review.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2018-11-06
    I Bellos,G Fitrou,V Pergialiotis,D N Perrea,G Daskalakis

    OBJECTIVE To determine the difference of serum levels of 10 adipokines (apelin, chemerin, fatty acid-binding protein-4, fibroblast growth factor-21, monocyte chemoattractant protein-1, nesfatin-1, omentin-1, resistin, vaspin, and visfatin) among women with gestational diabetes and healthy pregnant controls. MATERIALS AND METHODS Literature search was conducted using the Medline (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2018), Clinicaltrials.gov (2008-2018) and Google Scholar (2004-2018) databases, along with the reference list of the included studies. RESULTS Ninety-one studies were included in the present review, with a total number of 11,074 pregnant women. A meta-analysis was not conducted due to the high inter-study heterogeneity. Current evidence suggests that fatty acid-binding protein-4 levels are significantly increased in pregnancies complicated with gestational diabetes, while no association of serum apelin and monocyte chemoattractant protein-1 with the disease can be supported. Data regarding the rest adipokines are conflicting, since the available studies did not unanimously indicate a significant change of their levels in gestational diabetes. CONCLUSIONS The findings of the present systematic review suggest the promising role of fatty acid-binding protein-4 in the prediction of gestational diabetes, while inconsistent evidence exists regarding the rest novel adipokines. Future cohorts are needed to assess their predictive efficacy and fully elucidate their contribution in the disease.

    更新日期:2019-11-01
  • Hormonal and metabolic gender differences in a cohort of myotonic dystrophy type 1 subjects: a retrospective, case-control study.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-02
    M Spaziani,A Semeraro,E Bucci,F Rossi,M Garibaldi,M A Papassifachis,C Pozza,A Anzuini,A Lenzi,G Antonini,A F Radicioni

    PURPOSE Myotonic dystrophy type 1 (DM1) is a genetic disorder caused by CTG expansion in the DMPK gene. The aim was to investigate the endocrine and metabolic aspects of DM1. PATIENTS AND METHODS Retrospective, case-control study. We compared pituitary, thyroid, adrenal, gonadal and liver function and glycolipid metabolism of 63 DM1 patients against 100 control subjects. Given age-related differences, 2 further subgroups were created to investigate the pituitary-gonadal axis: < 41 (1a) and ≥ 41 (1b) years old for male subjects and < 46 (2a) and ≥ 46 (2b) years old for female subjects. Testicular and thyroid ultrasounds were also performed in the DM1 group. RESULTS FT3 and FT4 were significantly lower in DM1 men than controls, while for both males and females, thyroglobulin, ACTH and cortisol were significantly higher in the DM1 group. Gonadotropin levels were significantly higher and inhibin B and DHEA-S levels significantly lower in DM1 patients than controls for both male subgroups. Testosterone and SHBG were significantly higher in controls than in patients for subgroup 1a. Prolactin was significantly higher in patients in subgroups 1b, while testosterone was lower in subgroup 2a than in age-matched female controls. A correlation between the number of CTG repeats and the percentage of male hypogonadal subjects was found. Finally, there was a worse glucose and lipid pattern and significantly higher transaminase and gamma-GT levels in both male and female patients. CONCLUSIONS The high frequency of endocrine and metabolic abnormalities in DM1 highlights the importance of endocrine monitoring to enable the prompt initiation of a suitable therapy.

    更新日期:2019-11-01
  • DR10601, a novel recombinant long-acting dual glucagon-like peptide-1 and glucagon receptor agonist for the treatment of obesity and type 2 diabetes mellitus.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : 2019-12-02
    W Wang,X Wen,W Duan,X Wang,Y Chen,J Dong,Z Yang,J Fang,Z Zhou,G Yao,Y Fang,Y Huang

    PURPOSE Both glucagon-like peptide-1 (GLP-1) and glucagon (GCG) belong to the incretin family. This study aimed to investigate the pharmacokinetics and pharmacodynamics of DR10601, a fully recombinant hybrid peptide with dual GLP-1/GCG receptor agonistic activity. METHODS The agonistic ability of DR10601 was indirectly assessed by inducing cAMP accumulation in Chinese hamster ovary cells transfected with GLP-1R or GCGR in vitro. Following s.c. administration, the plasma pharmacokinetics of DR10601 were analysed in male Sprague-Dawley rats. The antiobesity effects and improved glycaemic control of DR10601 in vivo were evaluated by administering DR10601 to high-fat DIO mice and ICR mice as a single dose or repeated s.c. doses once every 4 days for 24 days. RESULTS DR10601 exhibits dual agonistic activity on GLP-1 and glucagon receptors. The plasma half-life of DR10601 in Sprague-Dawley rats following s.c. administration was 51.9 ± 12.2 h. In an IPGTT, a single s.c. dose of DR10601 (30 nmol/kg) produced similar glycaemic control effects and a longer duration of action compared to dulaglutide (10 nmol/kg). Compared with that achieved with liraglutide (40 nmol/kg) s.c. administered daily, DR10601 administered s.c. once every 4 days at 90 nmol/kg exerted a nearly equivalent effect on food intake and significantly reduced the body weights of high-fat DIO mice at 24 days. CONCLUSIONS Repeated administration of DR1060 provides potent and sustained glycemic control and body weight loss effect in high-fat DIO mice. DR10601 is a promising long-acting agent deserving further investigation for the treatment of type 2 diabetes and obesity.

    更新日期:2019-11-01
  • 更新日期:2019-11-01
  • Monitoring exercise intensity in diabetes: applicability of "heart rate-index" to estimate oxygen consumption during aerobic and resistance training.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    A L Colosio,G Spigolon,E Bacchi,P Moghetti,S Pogliaghi

    PURPOSE Accurate quantification and monitoring of exercise "dose", described by oxygen consumption (VO2), is necessary for exercise prescription and individualization. However, due to the complexity and elevated cost of direct, gold-standard methods, this is rarely done outside research laboratories. Heart rate-index (HRindex) is a new simple method to estimate VO2 in healthy and clinical populations. We tested the performance of HRindex to estimate VO2 in diabetic patients during aerobic (AT) and isotonic training (IT). METHODS Data from 12 males (age: 64 ± 5 years; BMI: 26 ± 12) with type 2 diabetes were analysed. VO2 and heart rate were measured during one AT and one IT session. Furthermore, VO2 was indirectly estimated based on HRindex. Then, the correspondence between measured and estimated VO2 was evaluated by two-way RM-ANOVA, correlation and Bland-Altman analysis. RESULTS Estimated average VO2 values during AT (1292 ± 366 ml/min) were not different from (p = 0.243) and highly correlated with (r = 0.87, p < 0.001) the measured values (1369 ± 417 ml/min), with a small bias and imprecision. Conversely during IT, HRindex overestimated VO2 compared to the actual measures (1048 ± 404 vs 667 ± 230 ml/min, p ≤ 0.001) and only a moderate correlation was found between values (r = 0.43, p ≤ 0.001), with a large bias and imprecision. CONCLUSION VO2 of aerobic exercises can be accurately estimated in diabetes patients using HRindex. During isotonic exercise, this method is not recommended for monitoring metabolic intensity due to large overestimation and imprecision. In aerobic exercise, HRindex offers a simple and valid alternative to the direct VO2 determination and may favour the applicability of time-resolved measures of exercise "dose".

    更新日期:2019-11-01
  • Perfluoro-octanoic acid impairs sperm motility through the alteration of plasma membrane.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    I Šabović,I Cosci,L De Toni,A Ferramosca,M Stornaiuolo,A Di Nisio,S Dall'Acqua,A Garolla,C Foresta

    CONTEXT Perfluoroalkyl-substances (PFAS) are chemical additives considered harmful for humans. We recently showed that accumulation of perfluoro-octanoic acid (PFOA) in human semen of exposed subjects was associated with altered motility parameters of sperm cells, suggesting direct toxicity. OBJECTIVES To determine whether direct exposure of human spermatozoa to PFOA was associated to impairment of cell function. PATIENTS AND METHODS Spermatozoa isolated from semen samples of ten normozoospermic healthy donors were exposed up to 2 h to PFOA, at concentrations from 0.1 to 10 ng/mL. Viability and motility parameters were evaluated by Sperm Class Analyser. Cell respiratory function was assessed by both mitochondrial probe JC-1 and respiratory control ratio (RCR) determination. Sperm accumulation of PFOA was quantified by liquid chromatography-mass spectrometry. Expression of organic ion-transporters OATP1 and SLCO1B2 was assessed by immunofluorescence and respective role in PFOA accumulation was evaluated by either blockade with probenecid or membrane scavenging through β-cyclodextrin (β-CD). Plasma membrane fluidity and electrochemical potential (ΔΨp) were evaluated, respectively, with Merocyanine-540 and Di-3-ANEPPDHQ fluorescent probes. RESULTS Compared to untreated controls, a threefold increase of the percentage of non-motile sperms was observed after 2 h of exposure to PFOA regardless of the concentration of PFOA, whilst RCR was significantly reduced. Only scavenging with β-CD was effective in reducing PFOA accumulation, suggesting membrane involvement. Altered membrane fluidity, reduced ΔΨp and sperm motility loss associated with exposure to PFOA were reverted by β-CD treatment. CONCLUSION PFOA alters human sperm motility through plasma-membrane disruption, an effect recovered by incubation with β-CD.

    更新日期:2019-11-01
  • Towards the tailoring of glucocorticoid replacement in adrenal insufficiency: the Italian Society of Endocrinology Expert Opinion.
    J. Endocrinol. Investig. (IF 3.439) Pub Date : null
    A M Isidori,G Arnaldi,M Boscaro,A Falorni,C Giordano,R Giordano,R Pivonello,C Pozza,E Sbardella,C Simeoli,C Scaroni,A Lenzi,

    CONTEXT Glucocorticoid (GC) replacement therapy in patients with adrenal insufficiency (AI) is life saving. After over 50 years of conventional GC treatment, novel formulations are now entering routine clinical practice. METHODS Given the spectrum of medications currently available and new insights into the understanding of AI, the authors reviewed relevant medical literature with emphasis on original studies, prospective observational data and randomized controlled trials performed in the past 35 years. The Expert Opinion of a panel of selected endocrinologists was sought to answer specific clinical questions. The objective was to provide an evidence-supported guide, for the use of GC in various settings from university hospitals to outpatient clinics, that offers specific advice tailored to the individual patient. RESULTS The Panel reviewed available GC replacement therapies, comprising short-acting, intermediate and long-acting oral formulations, subcutaneous formulations and the novel modified-release hydrocortisone. Advantages and disadvantages of these formulations were reviewed. CONCLUSIONS In the Panel's opinion, achieving the optimal GC timing and dosing is needed to improve the outcome of AI. No-single formulation offers the best option for every patients. Recent data suggest that more emphasis should be given to the timing of intake. Tailoring of GS should be attempted in all patients-by experts-on a case-by-case basis. The Panel identified specific subgroups of AI patients that could be help by this process. Long-term studies are needed to confirm the short-term benefits associated with the modified-release GCs. The impact of GC tailoring has yet to be proven in terms of hospitalization rate, morbidity and mortality.

    更新日期:2019-11-01
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