Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
Advance online publication
Showing 1-34 articles out of 34 articles from Advance online publication
  • Ann-Rong Yan, Xiaojuan Zhang, Hong Shen, Xia Zhou, Rui Li, Zhexing Yua ...
    Type: Original
    Article ID: EJ18-0532
    Published: 2019
    [Advance publication] Released: March 19, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Excessive iodine intake has been associated with increased risk of thyroid cancer (TC) in many studies, but the results have not been consistent. Since it was common knowledge that urinary iodine (UI) is considered a sensitive marker of current iodine intake, we conducted a meta-analysis to clarify the association between high UI and TC. We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, and the Cochrane Collaboration. Between-group meta-analyses were performed to compare UI between TC patients and the healthy/euthyroid subjects in local residents and benign thyroid nodules (BTN) patients. Then, between-group meta-analyses to compare the incidence rate of iodine excess were also conducted. The 22 case-control studies included in the meta-analyses represented 15,476 participants. It is the first time to clarify that UI was increased in PTC patients, but was not altered by regional population iodine intake status. Compared with BTN patients, PTC patients exhibited both higher UIC and higher odds ratio of iodine excess only in adequate iodine intake status subgroup; UIC, not the odds ratio of iodine excess, was higher in patients with PTC than those with BTN in above requirements iodine intake subgroup. A novel insight is offered that high UI in PTC patients was less influenced by regional population iodine intake status. It is indicted that high iodine intake is not a risk factor for PTC and high urinary iodine is just a specific characteristic of the disease.

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  • Yuko Asari, Kazunori Kageyama, Aya Sugiyama, Hikaru Kogawa, Kanako Nii ...
    Type: Original
    Article ID: EJ18-0491
    Published: 2019
    [Advance publication] Released: March 15, 2019
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    Cushing’s disease is almost always caused by hypersecretion of adrenocorticotropic hormone (ACTH) from a pituitary adenoma. A mutation in the deubiquitinase gene USP8 has been found in human ACTH-producing pituitary adenoma cells. This mutational hotspot hyperactivates USP8, rescuing epidermal growth factor receptor (EGFR) from lysosomal degradation and ensuring its sustained signaling in Cushing’s disease. An EGFR inhibitor would be an effective anti-tumor agent in EGFR-related tumors. We investigated the effect of a potent dual tyrosine kinase inhibitor, lapatinib, on ACTH production and cell proliferation in AtT-20 mouse corticotroph tumor cells. Lapatinib decreased proopiomelanocortin (Pomc) mRNA levels and ACTH levels in AtT-20 cells and also inhibited cell proliferation, induced apoptosis, and decreased pituitary tumor-transforming gene 1 (Pttg1), a hallmark of pituitary tumors, mRNA levels. KSN/Slc nude mice were subcutaneously inoculated with AtT-20 cells. After 1 week, the mice were randomized either to control or lapatinib groups. The inhibitor decreased the tumor weight of AtT-20 allografts in vivo versus control mice. Lapatinib also significantly decreased Pomc and Pttg1 mRNA levels in the tumor and plasma ACTH and corticosterone levels in vivo. Thus, lapatinib decreases the ACTH production and proliferation of corticotroph tumor cells. An EGFR-targeting therapy could be an important treatment for Cushing’s disease.

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  • Miyuki Katai, Kanako Sakurai, Megumi Fujita, Mayumi Yamamoto, Mari Hot ...
    Type: Original
    Article ID: EJ18-0501
    Published: 2019
    [Advance publication] Released: March 15, 2019
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    The Japan Endocrine Society (JES) has the largest ratio of female membership among societies associated with Internal Medicine in Japan; half of female members are in their 20s or 30s at present. In 2009, JES organized the “JES-We-Can” committee to promote women’s career development. To evaluate the effectiveness of JES-We-Can, we investigated the gender balance of various activities at JES in fiscal 2009 and 2017. Significant gender-differences were not observed in the acquisition rate of board-certified endocrinologists (BCEs) aged <40 y in 2009 and 2017. However, the acquisition rate of BCEs among women aged ≥40 y was significantly lower than men in 2009. In 2017, the gender-difference among BCEs in this group (currently aged ≥50 y) has considerably improved, but is not resolved. The acquisition rate of certificated endocrine educators (CEEs) among women was still significantly lower than men at all ages in 2017. Since the ratio of women oral speakers or poster presenters at annual academic meetings have grown to equal or surpass the membership ratio, female members make efficient contributions to JES. The numbers of women chairpersons, symposiasts, lecturers and invited speakers have increased, but remain limited. JES-We-Can was found to be effective in reducing the gender gap in academic activities at JES, but JES-We-Can should support women more intensely to raise the rate of CEEs among all ages and BCEs currently over 50 y, and to promote more women into higher positions in JES in the future. These actions are expected to introduce new and diverse perspectives into academia.

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  • Takashi Koshikawa, Nao Fujita, Nanae Ueda, Yuko Ota, Eiichi Sasaki, Yo ...
    Type: Original
    Article ID: EJ18-0525
    Published: 2019
    [Advance publication] Released: March 14, 2019
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    We studied cytological specimens of conventional papillary thyroid carcinoma (PTC), follicular variant papillary thyroid carcinoma (FVPTC), and noninvasive follicular thyroid tumor with papillary-like nuclear features (NIFTP) (formerly noninvasive FVPTC) to identify useful cytological parameters for their differentiation. Cytological findings of invasive FVPTC and NIFTP were very similar to each other but differed from those of conventional PTC. Intranuclear cytoplasmic inclusions, true papillary cell clusters, monolayered cell sheets, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background were the observed characteristic features of conventional PTC. Microfollicular cell clusters and dense globules of colloids were characteristic features of invasive FVPTC and NIFTP. Scoring the eight parameters (intranuclear cytoplasmic inclusions, nuclear grooves, powdery chromatin, true papillary cell clusters, ropy colloids, multinucleate giant cells, psammoma bodies, and cystic background) readily distinguished NIFTP from conventional PTC, but could not distinguish NIFTP from invasive FVPTC. The average total score of NIFTP, invasive FVPTC, and conventional PTC were 2.60 ± 0.55, 2.63 ± 0.62, and 4.57 ± 0.99, respectively. The difference between conventional PTC and NIFTP or invasive FVPTC was statistically significant (p < 0.001, Student’s t-test). Individuals with more than three of the identified parameters likely harbor conventional PTC, rather than NIFTP. In this way, 87.5% (112/128) of conventional PTCs could be differentiated from NIFTP, and definitively diagnosed as malignant by cytology.

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  • Kazuhiro Ueda, Atsushi Kiyota, Mariko Tsuchida, Mikako Okazaki, Nobuak ...
    Type: Original
    Article ID: EJ18-0469
    Published: 2019
    [Advance publication] Released: March 08, 2019
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    Myxedema coma is a rare endocrine emergency resulting from the decompensation of severe hypothyroidism, which is associated with a high mortality rate. It is characterized by the deterioration of mental status, hypothermia, hypotension, hyponatremia, and hypoventilation. Early disease diagnosis and advancements in intensive supportive care have reduced the mortality rate. Besides intensive supportive care, appropriate management of the underlying thyroid hormone deficiency is essential. However, as the disease is rare and unrecognized, evidence-based treatment of myxedema has not yet been established in many countries. An 84-year-old Japanese man with a history of Hashimoto’s thyroiditis was referred to our hospital. On arrival, conscious disturbance, hypothermia, hypotension, and hypoventilation were observed. He had discontinued thyroid hormone replacement therapy for a year. He was diagnosed with myxedema coma. Immediately, he received intensive supportive care and a combination therapy of 200 μg levothyroxine and 50 μg liothyronine until the fifth hospital day. Subsequently, monotherapy with levothyroxine was continued at a dose of 150 μg daily. The thyroid hormone level reached the normal range a few days later, and cardiovascular disease did not develop during hospitalization. This case demonstrated the efficacy of the combination of levothyroxine and liothyronine in treating myxedema coma.

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  • Akemi Hara, Yuko Nakagawa, Keiko Nakao, Motoyuki Tamaki, Tetsuya Ikemo ...
    Type: Original
    Article ID: EJ18-0441
    Published: 2019
    [Advance publication] Released: March 06, 2019
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    Pancreatic polypeptide (PP) is a 36-amino acid peptide encoded by the Ppy gene, which is produced by a small population of cells located in the periphery of the islets of Langerhans. Owing to the high amino acid sequence similarity among neuropeptide Y family members, antibodies against PP that are currently available are not convincingly specific to PP. Here we report the development of mouse monoclonal antibodies that specifically bind to PP. We generated Ppy knockout (Ppy-KO) mice in which the Ppy-coding region was replaced by Cre recombinase. The Ppy-KO mice were immunized with mouse PP peptide, and stable hybridoma cell lines producing anti-PP antibodies were isolated. Firstly, positive clones were selected in an enzyme-linked immunosorbent assay for reactivity with PP coupled to bovine serum albumin. During the screening, hybridoma clones producing antibodies that cross-react to the peptide YY (PYY) were excluded. In the second screening, hybridoma clones in which their culture media produce no signal in Ppy-KO islets but detect specific cells in the peripheral region of wild-type islets, were selected. Further studies demonstrated that the selected monoclonal antibody (23-2D3) specifically recognizes PP-producing cells, not only in mouse, but also in human and rat islets. The monoclonal antibodies with high binding specificity for PP developed in this study will be fundamental for future studies towards elucidating the expression profiles and the physiological roles of PP.

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  • Sadegh Rajabi, Mohammad Hossein Dehghan, Romina Dastmalchi, Farideh Ja ...
    Type: Review
    Article ID: EJ18-0537
    Published: 2019
    [Advance publication] Released: March 06, 2019
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    Thyroid cancer is the most prevalent endocrine cancer worldwide. Angiogenesis, the formation of new blood vessels, plays a pivotal role in the development and progression of tumors. Over the past years, cancer research has focused on the ability of tumors to induce newly formed blood vessel, because tumor growth and the process of cancer metastasis mainly depends on angiogenesis. Tumor neovascularization occurs following the imbalance between pro-angiogenic and anti-angiogenic factors until the tumor switches to an angiogenic phenotype. A number of signaling factors and receptors that are implicated in the regulation of angiogenesis have been identified and characterized; most notably, the vascular endothelial growth factors (VEGFs) family and their receptors, which are the main pro-angiogenic molecules during early development and in pathological conditions such as cancer. Although thyroid is a highly vascularized organ, angiogenic switch in tumors of this organ leads to the formation of a vast network of blood vessels that favors the dissemination of tumor cells to distant organs and results in deterioration of patient conditions. Accordingly, the identification of key angiogenic biomarkers for thyroid cancer can facilitate diagnosis, prognosis and clinical decision-making and also may help to discover targeting factors for effective cancer therapy as well as monitoring response to therapy. Hence, the main purposes of this review are to summarize the types and mechanisms of angiogenesis emphasizing the prominent factors implicated in thyroid cancer angiogenesis.

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  • Xiuying Zhang, Yufeng Li, Xianghai Zhou, Xueyao Han, Ying Gao, Linong ...
    Type: Original
    Article ID: EJ18-0140
    Published: 2019
    [Advance publication] Released: March 05, 2019
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    The relationship between variations in thyroid function and indices of obesity remains a focus of debate. To explore the associations between thyroid function within the normal range and obesity and to evaluate potential modifying factors, we analyzed a large and well-characterized community cohort in Beijing, China, containing 1,816 men and 1,774 women with serum thyrotropin (TSH) levels within the reference range (0.55–4.78 μIU/mL). Associations between TSH levels and BMI were identified using correlation analysis, ANOVA and Chi-square tests. Logistic regression analyses were used to estimate the impact of serum TSH on obesity before and after adjustment for possible confounding factors. The mean serum TSH was 2.04 ± 0.94 μIU/mL. TSH within the reference range was positively associated with BMI in both genders. Compared with euthyroid adults whose TSH was in the middle quartiles (TSH 1.30–2.60 μIU/mL) of the reference range, the odds of obesity (BMI ≥ 28.0 kg/m2) and severe obesity (BMI ≥ 33.0 kg/m2) was 38% (OR = 1.38, 95% CI 1.17–1.64) and 58% (OR = 1.58, 95% CI 1.12–2.21) more likely, respectively, among those with TSH in the upper quartile. For women, postmenopausal subjects with lower TSH levels had a lower risk of severe obesity (OR = 0.42, 95% CI 0.20–0.91) than those in the middle TSH quartile. Positive associations were found between serum TSH within the euthyroid range and obesity, and menopause showed a significant influence on the relationship between TSH level and severe obesity.

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  • Daisuke Watanabe, Hideaki Yagasaki, Satoru Kojika, Masakazu Ogiwara, H ...
    Type: Original
    Article ID: EJ18-0370
    Published: 2019
    [Advance publication] Released: February 28, 2019
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    GH-secreting pituitary adenomas (GHomas) are rare in the pediatric population. Guanine nucleotide-binding protein, alpha stimulating (GNAS) somatic mutations are often found in patients with GHoma. Here, we report an 8-year-old girl with GH-secreting pituitary adenoma successfully treated by operative tumor resection and postoperative treatment with octreotide long-acting release (LAR). Tumor DNA sequence analysis revealed a somatic heterozygous c.680A>T (p.Gln227Leu) mutation in GNAS. We reviewed 1,084 cases of GHomas, 409 (37.7%) of which harbored GNAS mutations. In pediatrics cases, aged 15 years or younger, 11 harbored a GNAS mutation, and GNAS p.Arg201Cys was identified in five cases. No other cases of codon 227 mutation were detected. These cases suggest that, in pediatric patients, the clinical features of GHoma may differ from those observed in adults. This is possibly related to octreotide or dopamine agonist resistance. Of six patients with surgical resistance, only one was reactive when treated with octreotide. Our case shows that octreotide LAR is an effective choice for treating GNAS-induced GHoma. This is the first report detailing the effectiveness of octreotide LAR in a GNAS codon 227 mutation-induced GHoma in a pediatric case. Examination of the relationship between genetic variation and clinical features in pediatric patients will enable us to assess the long-term effects of surgical and medical treatment of GHomas.

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  • Huiyan Wang, Guangtong She, Wenbai Zhou, Kezhuo Liu, Jun Miao, Bin Yu
    Type: Original
    Article ID: EJ18-0291
    Published: 2019
    [Advance publication] Released: February 27, 2019
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    Forty-five pregnant women who underwent cesarean section, including 30 cases of gestational diabetes mellitus (GDM) and 15 normal pregnant women, were enrolled in this study to examine the differential expression of circular RNAs (circRNAs) in the placentas of women with GDM by RNA sequencing (RNA-seq) analysis. The differentially expressed circRNAs were analyzed bioinformatically using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and circRNA-microRNA (miRNA) interaction prediction. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the results. A total of 8,321 circRNAs were identified in the human placenta, among which 46 were differentially expressed (fold change ≥2 and p < 0.05), including three that were upregulated and 43 that were downregulated. According to the GO and KEGG enrichment results, these circRNAs may be associated with vital biological processes, cellular components, molecular functions, and signaling pathways. In particular, KEGG analysis shown they may be involved in advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE) signaling pathway in diabetic complications, indicating that these circRNAs might participate in the occurrence and pathogenesis of GDM. qRT-PCR verified that the expression of circ_5824, circ_3636, and circ_0395 was consistent with RNA-seq analysis; their expression levels were significantly lower in the GDM group than in the control group. The circRNA-miRNA interaction was analyzed according to the molecular sponge mechanism, and its potential function is discussed. These results shed light on future functional studies of circRNAs related to GDM.

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  • Sumie Okahata, Kentaro Sakamoto, Takako Mitsumatsu, Yuko Kondo, Shinsu ...
    Type: Original
    Article ID: EJ18-0328
    Published: 2019
    [Advance publication] Released: February 27, 2019
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    Therapeutic blocking antibodies against programmed death 1 (PD1) and cytotoxic T-lymphocyte antigen 4 (CTLA4) are applied for advanced cancer therapy, but induce a wide range of immune-related adverse events. In our recent case of a 52-year-old female doctor suffering from breast cancer having metastasized to the lung and liver, it was decided to use nivolumab to prevent the disease progressing after excisional surgeries and multiple chemotherapies. One month after completing the nivolumab course, fatigue, hypoglycemia and hypotension developed and isolated ACTH deficiency (IAD) was diagnosed. A further month later, under steroid supplementation, hyperglycemia emerged alongside thirst and polydipsia, prompting a diagnosis of fulminant type 1 diabetes (FT1D). Her susceptibility to type 1 diabetes was examined by HLA haplotype and CTLA4 gene polymorphism analyses. Polymorphisms CT60G>A and +49G>A in CTLA4 both generated a GG genotype. Our patient manifested one of the rarest combinations of autoimmune disease induced by nivolumab. Whereas the HLA haplotype was unsusceptible to autoimmune type 1 diabetes, polymorphisms of CTLA4, the antibody of which frequently causes hypophysitis, were susceptible to FT1D. Peripheral modulation of activated T cells, mainly by PD-1 antibodies, induced FT1D associated with IAD in patients with CTLA4 polymorphism. This case reveals hints of the T-cell etiology in T1D and evidence of CTLA4 involvement in IAD.

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  • Aya Yoshihara, Yuqian Luo, Yuko Ishido, Kensei Usukura, Kenzaburo Oda, ...
    Type: Original
    Article ID: EJ18-0380
    Published: 2019
    [Advance publication] Released: February 27, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Methimazole (MMI) and propylthiouracil (PTU) are commonly used for the treatment of Graves’ disease. They share similar inhibitory effects on thyroid hormone biosynthesis by interfering with thyroid peroxidase (TPO)-mediated oxidation and organification of iodine. However, their potential effects on other thyroid functional molecules have not been explored in depth. To identify novel effects of MMI and PTU, DNA microarray analysis, real-time PCR, Western blotting, immunofluorescence staining and confocal laser scanning microscopy were performed using FRTL-5 rat thyroid cells. DNA microarray analysis indicated that both MMI and PTU suppress iodotyrosine deiodinase 1 (Iyd, Dehal1) mRNA levels. Further studies revealed that Dehal1 mRNA levels was stimulated by TSH, insulin and serum, while it was suppressed by iodine and a follicular concentration of thyroglobulin. MMI and PTU significantly suppressed Dehal1 expression induced by TSH, insulin and serum. On the other hand, although MMI suppressed Dehal1 expression in the absence of TSH, PTU only weakly suppressed Dehal1 without TSH. These results suggest that PTU and MMI may use different mechanisms to regulate Dehal1 expression, and TSH may play essential and differential roles in mediating PTU and MMI signals in thyrocytes. The drugs also inhibited re-distribution of Dehal1 protein into newly formed lysosomes following thyroglobulin endocytosis. These findings imply complex and multifaceted regulation of Dehal1 in the thyroid and suggest that MMI and PTU modulate Dehal1 expression and distribution of the protein in thyrocytes to exert their effect.

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  • Tatjana Zake, Sandra Skuja, Ieva Kalere, Ilze Konrade, Valerija Groma
    Type: Original
    Article ID: EJ18-0396
    Published: 2019
    [Advance publication] Released: February 27, 2019
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    T helper (Th) 17 cells and interleukin (IL)-17 play a significant role in the pathogenesis of autoimmune thyroid disease (AITD). However, it has recently become clear that Th17 cells are more heterogeneous and exhibit two different phenotypes, whereas IL-23 and IL-1β are crucial for the generation of pathogenic Th17 lymphocytes. We aimed to investigate the association between IL-17 and Th17-promoting cytokines in AITD by studying the immunoexpression patterns of IL-17, IL-23, and IL-1β in thyroid tissue. Following thyroidectomy, 29 patients with AITD (21 cases of Hashimoto’s thyroiditis (HT) and 8 cases of Graves’ disease (GD)) and 18 patients with colloid goiter, as controls, were enrolled in this study, and immunohistochemistry was performed. The expression level of IL-17 in thyrocytes was significantly higher in HT and GD patients than in colloid goiter patients. Immunopositivity for both IL-23 and IL-1β was significantly increased in HT patients compared to GD and colloid goiter patients. However, no difference was found between IL-23 or IL-1β expression in patients with GD and colloid goiter. A positive correlation between IL-17 and IL-23 as well as IL-17 and IL-1β expression was observed in HT patients (r = 0.574, p = 0.007 and r = 0.461, p = 0.036, respectively). In the GD group, IL-17 was positively correlated with IL-1β (r = 0.817, p = 0.013) but not with IL-23 expression. We found increased IL-23 and IL-1β expression in the HT group but not in the GD group. Furthermore, both interleukins were correlated with IL-17 immunopositivity in thyroid tissue, suggesting that pathogenic Th17-promoting cytokines may play a role in HT pathogenesis.

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  • Takahiro Nojiri, Makoto Kurano, Osamu Araki, Kazuki Nakawatari, Masako ...
    Type: Original
    Article ID: EJ18-0451
    Published: 2019
    [Advance publication] Released: February 27, 2019
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    Graves’ Disease is a representative autoimmune thyroid disease that presents with hyperthyroidism. Emerging evidence has shown the involvement of lysophosphatidic acid (LPA) and its producing enzyme, autotaxin (ATX), in the pathogenesis of various diseases; among them, the involvement of the ATX/LPA axis in some immunological disturbances has been proposed. In this study, we investigated the association between serum ATX levels and Graves’ disease. We measured the levels of serum total ATX and ATX isoforms (classical ATX and novel ATX) in patients with untreated Graves’ disease, Graves’ disease treated with anti-thyroid drugs, patients with subacute thyroiditis, silent thyroiditis, Plummer’s disease, or Hashimoto’s thyroiditis, and patients who had undergone a total thyroidectomy, as well as normal subjects. The serum total ATX and ATX isoform levels were higher in the patients with Graves’ disease, compared with the levels in the healthy subjects and the patients with subacute thyroiditis. Treatment with anti-thyroid drugs significantly decreased the serum ATX levels. The serum ATX levels and the changes in serum ATX levels during treatment were moderately or strongly correlated with the serum concentrations or the changes in thyroid hormones. However, the administration of T3 or T4 did not increase the expression or serum levels of ATX in 3T3L1 adipocytes or wild-type mice. In conclusion, the serum ATX levels were higher in subjects with Graves’ disease, possibly because of a mechanism that does not involve hyperthyroidism. These results suggest the possible involvement of the ATX/LPA axis in the pathogenesis of Graves’ disease.

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  • Simone Ciuffi, Luisella Cianferotti, Gabriella Nesi, Ettore Luzi, Fran ...
    Type: Original
    Article ID: EJ18-0387
    Published: 2019
    [Advance publication] Released: February 22, 2019
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    Hyperparathyrodism-jaw tumor (HPT-JT) syndrome is an autosomal dominant disorder. Loss of function of the cell division cycle protein 73 homolog (CDC73) gene is responsible for the syndrome. This gene encodes an ubiquitously expressed 531 amino acid protein, parafibromin, that acts as a tumor suppressor. Loss of heterozygosity (LOH) of the CDC73 locus in many HPT-JT associated parathyroid tumors from patients with germline mutation is in accordance with Knudson’s “two-hit” model for hereditary cancer. A 41-year-old man with mandible ossifying fibroma suffered from severe hypercalcemia due to parathyroid carcinoma (PC). Genetic analysis was performed to evaluate germinal and somatic CDC73 gene mutation as well as real-time qRT-PCR to quantify CDC73 mRNA, miR-155 and miR-664 expression levels. Immunohistochemistry and Western blotting (WB) assay were carried out to evaluate parafibromin protein expression. A novel heterozygous nonsense mutation, c.191-192 delT, was identified in the CDC73 gene. No CDC73 LOH was found in PC tissue, nor any differences in expression levels for CDC73 gene, miR-155 and miR-664 between PC and parathyroid adenoma control tissues. On the contrary, both immunohistochemistry and WB assay showed an approximate 90% reduction of parafibromin protein expression in PC. In conclusion, this study describes a novel germinal mutation, c.191-192 delT, in the CDC73 gene. Despite normal CDC73 gene expression, we found a significant decrease in parafibromin. We hypothesize that a gene silencing mechanism, possibly induced by microRNA, could play a role in determining somatic post-transcriptional inactivation of the wild type CDC73 allele.

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  • Ying Li, Wei Guan, Shuai Ma, Shibo Lin, Ningli Yang, Ruiping Liu, Hui ...
    Type: Original
    Article ID: EJ18-0446
    Published: 2019
    [Advance publication] Released: February 22, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Obesity is linked to a low-grade systemic inflammation and lipopolysaccharide (LPS) is a key factor. Sleeve gastrectomy (SG) can significantly cause weight loss, but few reports have looked into the changes of LPS and inflammatory cytokines after surgery. To explore the potential short-term impact of SG on LPS and inflammatory cytokines and their relationship to early metabolic changes in obesity. 30 Chinese adults with obesity (BMI 39.37 ± 8.22 kg/m2, 25 female) receiving SG were included in this study. Fasting blood samples were collected at baseline and 30 days after SG. Serum LPS markedly reduced from 336.50 (73.54, 500) pg/mL to 5.00 (5.00, 5.24) pg/mL at 1 month after SG (p < 0.05). There was a significant decrease in plasma IL-6, IL-8, and serum CRP after SG (all p < 0.05). Insulin resistance improved remarkably after surgery as displayed by reductions in fasting insulin level (FINS, p < 0.001), and HOMA-IR (p < 0.001). In addition, visceral fat area (VFA) decreased from 209.70 ± 39.96 cm2 to 193.28 ± 43.68 cm2 after SG (p < 0.001). LPS was positively correlated with FINS (r = 0.391, p = 0.033) and HOMA-IR (r = 0.38, p = 0.038) before SG. Meanwhile, VFA was positively associated with CRP (r = 0.388, p = 0.034) before surgery. When assessing 30-days postoperative changes, a positive correlation was found between the variations of LPS, IL-8 and the reduction of VFA. After multivariate analyses, only the reduced IL-8 level was independently associated with the reduction of VFA (p = 0.015). In conclusion, SG can significantly relieve the inflammation in obesity in the short term and LPS might be an earlier predictor of inflammatory changes after surgery.

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  • Kanako Tanase-Nakao, Kentaro Mizuno, Yutaro Hayashi, Yoshiyuki Kojima, ...
    Type: Note
    Article ID: EJ18-0494
    Published: 2019
    [Advance publication] Released: February 19, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Endogenous and exogenous androgens induce masculinization of external genitalia through binding to the androgen receptor (AR). The target genes of androgens in external genitalia remain to be determined, although previous studies have shown that the apolipoprotein D gene (APOD) was significantly upregulated by dihydrotestosterone (DHT), the most potent androgen in humans. In the present study, we performed microarray analysis for genital skin fibroblasts obtained from four boys with buried penis (the control individuals) and a patient with partial androgen insensitivity syndrome (PAIS) due to a hypomorphic mutation in AR (the PAIS patient). We identified 24 transcripts that were upregulated or downregulated by DHT in all samples of control individuals and, to a lesser extent, in the sample of the PAIS patient. Differences between DHT-treated and -untreated samples were small; the results of 24 transcripts did not reach statistical significance. The 24 transcripts included CYP1B1, a gene possibly involved in the development of genital tubercle in mice, and APOD, as well as several genes that have been reported as androgen targets in prostate or other tissues. The results of this study indicate that androgen-mediated masculinization of external genitalia is unlikely to depend on massive transcriptional changes in specific AR target genes. Rather, minor transcriptional changes of several genes, and/or a complex molecular network may play a major role in penile development. Importantly, our data suggest the possible involvement of CYP1B1 in human genital development and confirm the clinical importance of APOD as a biomarker for AR function.

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  • Daigo Saito, Yoichi Oikawa, Gen Mizutani, Kazuyuki Inoue, Masako Hatan ...
    Type: Original
    Article ID: EJ18-0417
    Published: 2019
    [Advance publication] Released: February 14, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    This research aimed to examine the relationship between anti-glutamic acid decarboxylase antibody (GADA) titers and clinical parameters at onset and to clarify the association between clinical severity and GADA titers in GADA-positive fulminant type 1 diabetes. This cross-sectional observational study included 20 cases with GADA-positive fulminant type 1 diabetes (4 cases from our hospital and 16 from cases reported in the literature). The association between GADA titers and clinical parameters [age, sex, body weight, body mass index, period from appearance of any prodromal symptoms to diagnosis, period from development of hyperglycemic symptoms to diagnosis, GADA titer, HbA1c level, blood pH and HCO3 level, serum levels of ketone bodies and pancreatic exocrine enzymes] were analyzed. Spearman’s rank correlation coefficient (rs) was used for the correlation analysis. The results showed that there was a significant inverse correlation between GADA titers and the “period from appearance of any prodromal symptoms to diagnosis” (rs = –0.559, p < 0.05). Moreover, GADA titers were inversely correlated with blood pH and HCO3 level (rs = –0.576, p < 0.05, rs = –0.578, p < 0.05, respectively), and positively correlated with serum levels of total ketone bodies, acetoacetate, and 3-hydroxybutyrate (rs = 0.661, p < 0.05; rs = 0.700, p < 0.05; and rs = 0.782, p < 0.01, respectively). These findings suggest that higher GADA titers may be linked to more severe clinical severity of GADA-positive fulminant type 1 diabetes at onset. This association may be attributed to possible pre-existence of autoimmunity-related β-cell damage before the onset of fulminant type 1 diabetes.

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  • Noriaki Fukuhara, Naoko Inoshita, Mitsuo Yamaguchi-Okada, Keita Tatsus ...
    Type: Original
    Article ID: EJ18-0458
    Published: 2019
    [Advance publication] Released: February 14, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Pituitary adenoma has been reported to be detectable in only 36–63% of Cushing’s disease (CD) patients by magnetic resonance imaging (MRI). In this study, we investigate the outcomes and problems associated with tumor identification using 3-Tesla (3-T) MRI, which provides clearer images than ≤1.5-T MRI, in 115 patients who were initially diagnosed with CD. Before surgery, 31 macroadenomas (27%) and 54 microadenomas (47%) were identified by 3-T MRI, but pituitary adenoma was invisible on MRI in the remaining 30 cases (26%). The smallest tumor diameter amenable to a definitive diagnosis was 2 mm, and spoiled gradient-echo was the best sequence for diagnosing microadenomas. In 14 of 30 cases of MRI-invisible CD, the pituitary adenoma was identified during surgery. Nine of these 14 tumors that developed from outside the pituitary gland were retrospectively identified on MRI by comparison with surgical findings. The remaining 16 cases of MRI-invisible CD in which the pituitary adenoma was not identified during surgery involved partial hypophysectomy. Seven cases were hormonally remitted, but another nine cases experienced persistent disease after surgery. The sensitivity and specificity of the pituitary adenoma diagnosis in CD patients after the introduction of 3-T MRI were 80% and 100%, respectively. However, the sensitivity decreased to 72% when macroadenomas were excluded. Some adenomas associated with CD are still undetectable on 3-T MRI due to tumor size, location and intensity. However, sensitivity can be improved by monitoring tumors that develop outside the pituitary gland.

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  • Hui-Xuan Wu, Jun Tang, Long Li, Shi-Ping Liu, Zhi-Guang Zhou, Jian-Xin ...
    Type: Original
    Article ID: EJ18-0560
    Published: 2019
    [Advance publication] Released: February 13, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Type 2 diabetic patients are becoming younger and having a tendency to family aggregation, they are easily suspected as maturity-onset diabetes of young (MODY) in the outpatient clinic and send to genetic testing. 9 diabetic families were compared in our outpatient clinic who met the primary diagnosis criteria of MODY. Detailed clinical features and laboratory data including gene sequence were collected and analyzed. The patients met the primary clinical diagnostic criteria of MODY for genetic testing at the first look. However, members of families A1 to A3 had normal Body mass index (BMI) and a lower C-peptide level which indicated impaired pancreatic islet function. In contrast, the members with diabetes of families B1 to B6 had normal or increased C-peptide level which indicated insulin resistance and were overweight with BMI. Genetic testing showed that the mutations in HNF1A, INS, KCNJ11 and so on in families A were consistent with the diagnosis of MODY. No pathogenic mutation was found in the members of families B which were diagnosed with familial T2D. Before the clinical laboratory testing and the further gene test, BMI and the concentration of C-peptide are important for the promptly differential diagnosis of MODY from familial type 2 diabetes and medication instruction in the outpatient clinic which could help to alleviate the burden of genetic testing for them.

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  • Seyfullah Kan, Muhammed Kizilgul, Bulent Celik, Selvihan Beysel, Musta ...
    Type: Original
    Article ID: EJ18-0502
    Published: 2019
    [Advance publication] Released: February 09, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Nodular thyroid disease is a very common disorder in patients with acromegaly. Insulin-like growth factor-1 (IGF-1) is a thyroid growth factor, and there is a correlation between IGF-1 levels and thyroid volume (TV) in patients with acromegaly. There is no study investigating the impact of somatostatin analog (SSA) treatment on thyroid nodule volume in patients with acromegaly. We aimed to assess thyroid nodule volume change with SSA treatment in patients with persistent acromegaly. We retrospectively analyzed data from 108 consecutive patients with acromegaly who were followed up by our clinic after undergoing surgery between 2002 and 2014. Patients who were cured after surgery were excluded. We only selected 43 patients (21 males, 22 females, mean age 52.8 ± 11.9 years) who did not meet the criteria of remission postoperatively, who were treated with SSA for at least six months and had normal thyroid function. Patients were divided into three groups (well-controlled, controlled, and active) according to their IGF-1 and growth hormone (GH) levels. All patients underwent an evaluation of TV and total thyroid nodule volume (TTNV) by ultrasound. TTNV decreased significantly in patients with well-controlled acromegaly (0.44 [0.75] to 0.23 [0.73], p < 0.001). TTNV did not change in controlled patients (0.18 [1.28] to 0.13 [1.54], p = 0.959); however TTNV increased in patients with active acromegaly (0.77 [1.46] to 1.03 [1.88], p = 0.028). Successful medical treatment of patients with active acromegaly decreases thyroid nodule volume. Sustained exposure to IGF-1 may cause an increase in thyroid nodule volume in patients with acromegaly.

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  • Sun-Young Lee, Deog-Yoon Kim, Mi Kyung Kwak, Seong Hee Ahn, Hyeonmok K ...
    Type: Original
    Article ID: EJ18-0352
    Published: 2019
    [Advance publication] Released: February 08, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    The inflammatory biomarkers that fully characterize the metabolically unhealthy (MU) state—which is a risk factor for cardiovascular disease (CVD)—remain unclear. Recent studies suggest follistatin-like protein 1 (FSTL1) could be used as a biomarker for inflammation and CVD, however there is little information on FSTL1 levels in the MU state. We aimed to evaluate the associations between FSTL1, the presence of MU state and subclinical coronary atherosclerosis. In a cross-sectional study, we evaluated FSTL1 levels and their relationship with the presence of MU state and coronary artery plaques in 230 Korean patients. Significant increase in FSTL1 levels was observed in subjects with MU state (p = 0.020), but not those with obesity state according to body mass index criteria (p = 0.790). After adjusting for confounders, the odd ratio (OR) for the MU state among patients in the highest FSTL1 tertile (T3) was higher in comparison with the lowest tertile (T1) (OR = 3.60, 95% confidence interval [95% CI] = 1.20–10.83). In a subgroup (n = 66), FSTL1 levels were also marginally higher in patients with plaques (p = 0.098). The OR for plaque presence in patients with T3 was significantly higher in comparison with T1 after adjusting for confounders (OR = 12.51, 95% CI = 1.15–135.73). Plasma FSTL1 may be a useful biomarker for the risk of MU state and CVD.

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  • Minsun Jung, Jeong Mo Bae, Yoon Kyung Jeon, Kyeong Cheon Jung, Sun Woo ...
    Type: Note
    Article ID: EJ18-0428
    Published: 2019
    [Advance publication] Released: February 05, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Parathyroid adenoma with prominent lymphocytic infiltrate is a rare disease. Until now, 11 patients have been reported. Herein, we report a 57-year-old man who had a neck mass that was incidentally found. Aspiration cytology and subsequent needle biopsy of the tumor were performed and suggested papillary thyroid carcinoma. From the resected specimen, however, the patient was finally diagnosed with parathyroid adenoma with prominent lymphocytic infiltrate, characterized by hyperplastic parathyroid cells with nuclear atypia within fibrotic stroma along with numerous lymphocytes forming germinal centers. Some eosinophils and plasma cells were also observed with some histological features highly suggestive of IgG4-related disease (IgG4-RD), including increased IgG4-positive plasma cells and IgG4/IgG-positive plasma cell ratio, storiform-type fibrosis, and obliterative phlebitis. It turned out that microfollicular or trabecular architecture and cellular atypia with high expression of HBME-1 observed in the aspiration cytology and needle biopsy had been misinterpreted as a thyroid malignancy. This is the first report describing microscopic features of aspiration cytology and needle biopsy of parathyroid adenoma with prominent lymphocytic infiltrate, warning that it can mimic papillary thyroid carcinoma in biopsy specimens. Furthermore, the IgG4-RD-like features of the present case and previous reports imply that parathyroid adenoma with prominent lymphocytic infiltrate may be a type of IgG4-RD.

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  • Muhammad Majid Aziz, Shimin Yang, Imran Masood, Shan Zhu, Muhammad Ali ...
    Type: Original
    Article ID: EJ18-0429
    Published: 2019
    [Advance publication] Released: February 05, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    This study was conducted to assess quality of counseling provided to type 2 diabetic patients. For this cross-sectional study, a simulated patient method was applied in 562 selected community pharmacies of Punjab, Pakistan. A scenario for the metformin oral therapy was developed that illustrates direct counseling for adult diabetic patients. Counseling and communication skills were also assessed. Descriptive statistics and chi-square tests were used for analysis. Only 29.4% of simulated patients received medication counseling directly; 47.6% received it on request. About 32.8% of clients were referred to a physician without counseling. The most frequently provided information was dietary instruction (94.8%) and dose of therapy (84.5%). Only one quarter (25.3%) of simulated patients were asked about disease duration and similar rate (25.0%) was found for discussions of special warnings. The side effects, drug storage, drug–drug interactions and duration of therapy were ignored. Minimal information was provided about other medication during therapy (0.2%) and effect of medicine withdrawal (2.7%). About 59.5% simulated patients were instructed for compliance to medication. Counseling to type 2 diabetic patients in Pakistani community pharmacies is not very satisfactory. Pharmacies’ staff have little focus on counseling. Professional training of staff could improve counseling and communication skills.

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  • Yoshinori Yasuda, Shintaro Iwama, Hiroshi Arima
    Type: Original
    Article ID: EJ18-0545
    Published: 2019
    [Advance publication] Released: February 02, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Primary sclerosing cholangitis (PSC) has been known as a cause of secondary osteoporosis, which often requires medication. Herein, we give the first report of a case of a 38-year-old man with fatigue and paralysis in both upper limbs who had been treated with denosumab for secondary osteoporosis associated with PSC. Since bisphosphonate (alendronate) was ineffective in our patient, the treatment was changed from alendronate to denosumab. Despite replacements with calcium and active vitamin D (alfacalcidol; 1-hydroxycholecalciferol), he developed severe hypocalcemia (albumin-adjusted serum calcium: 5.2 mg/dL) 2 weeks after the second administration of denosumab, which required immediate correction. After that, the corrected serum calcium levels were controlled within the normal range with 0.75 μg of eldecalcitol (1α,25-dihydroxy-2β-(3-hydroxypropyloxy)vitamin D3) and increased doses of calcium (1,500 mg daily) and phosphate (900 mg daily) without denosumab. Even though denosumab treatment had been terminated, the T score of the lumbar spine improved from –4.4 to –‍2.6 by 1 year after the second administration, possibly due to the amelioration of osteomalacia through the treatment with eldecalcitol and the higher doses of calcium and phosphate. This report indicates that denosumab can cause severe hypocalcemia in patients with osteoporosis associated with chronic diseases of the hepatobiliary system including PSC, in turn suggesting that the possibility of vitamin D deficiency or osteomalacia should be considered before administering treatments and that serum calcium levels should be closely monitored to detect life-threatening hypocalcemia in patients who have high risk factors for hypocalcemia.

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  • Ting Lu, Yao Wang, Ting Dou, Bizhen Xue, Yuanyuan Tan, Jiao Yang
    Type: Original
    Article ID: EJ18-0436
    Published: 2019
    [Advance publication] Released: January 30, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    The pathogenesis of type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and β-cell dysfunction. Earlier studies reported that increased levels of pancreatic fat may lead to the development of β-cell dysfunction and insulin resistance. The present study aimed to demonstrate the relationship between pancreatic fat content (PFC) and insulin secretion and insulin resistance in Chinese subjects with T2DM. Seventy-eight T2DM subjects and 35 non-diabetic volunteers were recruited in this study. All subjects were subjected to an oral glucose tolerance test (OGTT). We also measured PFC and liver fat content (LFC) by three-point Dixon method (3p-Dixon), and we examined the relations between PFC and OGTT-derived parameters. T2DM subjects had higher PFC than non-diabetic subjects (p < 0.01). PFC was correlated with body mass index (BMI), liver fat content (LFC) and age in two groups, however, it was only positively associated with insulin secretion, insulin resistance, early- and late-phase insulin secretion in male T2DM subjects, but not in non-diabetic and female T2DM subjects. After adjusting for BMI, LFC and age, the association still existed (all p < 0.05). Furthermore, the relationship was more obvious in male T2DM subjects with a shorter course of disease. PFC was associated with β-cell dysfunction and insulin resistance in subjects with T2DM and was more obvious in male T2DM subjects with shorter duration of diabetes. Therefore, PFC might represent a potential risk factor for the development of T2DM.

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  • Tatsuya Kondo, Miwa Nakamura, Junji Kawashima, Takeshi Matsumura, Taka ...
    Type: Original
    Article ID: EJ18-0496
    Published: 2019
    [Advance publication] Released: January 29, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Although hyperemesis gravidarum (HG), an extreme form of morning sickness, is a common complication during pregnancy, HG associated simultaneous onset of rhabdomyolysis and diabetes insipidus due to electrolyte abnormalities are rare. A 34-year-old woman with severe HG at 17 weeks of gestation complicated with appetite loss, weight reduction by 17 kg, general fatigue, myalgia, weakness and polyuria was identified to have simultaneous hypophosphatemia (1.6 mg/dL) and hypokalemia (2.0 mEq/L). Appetite recovery and the improvement of the hypophosphatemia (3.2 mg/dL) were observed prior to the first visit to our department. At the admission, she presented polyuria around 7,000~8,000 mL/day with impaired concentrating activity (U-Osm 185 mOsm/L), and abnormal creatine kinase elevation (4,505 U/L). The electrolyte disturbances and physio-metabolic abnormalities in undernourished state due to HG let us diagnose this case as refeeding syndrome (RFS). In this case, abnormal loss by vomiting, insufficient intake and previous inappropriate fluid infusion as well as the development of RFS may accelerate the severity of hypokalemia due to HG. Thus, as her abnormalities were considered as results of rhabdomyolysis and diabetes insipidus due to severe HG associated hypokalemia based on RFS, oral supplementation of potassium chloride was initiated. After 6 days of potassium supplementation, her symptoms and biochemical abnormalities were completely resolved. Severe HG followed by RFS can be causes of electrolyte abnormalities and subsequent complications, including rhabdomyolysis and renal diabetes insipidus. Appropriate diagnosis and prompt interventions including adequate nutrition are necessary to prevent electrolyte imbalance induced cardiac, neuromuscular and/or renal complications.

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  • Kun Huang, Yeqing Xu, Shuangqin Yan, Tao Li, Yuanhong Xu, Peng Zhu, Fa ...
    Type: Original
    Article ID: EJ18-0340
    Published: 2019
    [Advance publication] Released: January 24, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    This article aims to understand the isolated effect of maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and antithyroid peroxidase antibodies (TPOAb) in early pregnancy on gestational diabetes mellitus (GDM). Based on a birth cohort, pregnant women presented to maternity hospitals for the first antenatal care from Nov 2008 to Oct 2010 were invited to participate in the study. A self-administered questionnaire was asked to complete to collect data on socio-economic variables, previous adverse pregnancy outcomes, method of conception, previous endocrinic and metabolic diseases, and pregnancy-related anxiety in 1st trimester of the index pregnancy. Pre-pregnancy BMI was measured. Serum samples were collected, and TSH, FT4 and TPOAb were assayed. GDM was confirmed from medical records screened on 24–28 gestational weeks by using oral glucose tolerance test (OGTT). The prevalence of isolated subclinical hypothyroidism, hypothyroidemia and positive TPOAb in early pregnancy was 2.0%, 2.0% and 12.8%. Prevalence of GDM in women with the isolated sub-clinical hypothyroidism, hypothyroxinemia and positive TPOAb was 2.9%, 2.8% and 3.1%, respectively, which were all higher than that detected in euthyroidism women (1.2%). Women with isolated positive TPOAb had significantly higher TSH and lower FT4 level compared with euthyroidism women. It was found that isolated positive TPOAb in early pregnancy increased the risk of GDM, adjusted RR and 95%CI being 2.541(1.037–6.226). No significant relationships were identified between isolated sub-clinical hypothyroidism or hypothyroxinemia with GDM. In conclusion, isolated thyroid autoimmunity, represented by positive TPOAb, in early pregnancy were associated with GDM independent of TSH and FT4.

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  • Yuichi Miyakawa, Kei Takasawa, Yohei Matsubara, Kenji Ihara, Yoshiaki ...
    Type: Original
    Article ID: EJ18-0326
    Published: 2019
    [Advance publication] Released: January 23, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Pseudohypoparathyroidism type 1A (PHP1A) is characterized by resistance to multiple hormones, the Albright Hereditary Osteodystrophy phenotype, obesity, and developmental delay. Developmental delay usually appears prior to hypocalcemia due to parathyroid hormone resistance and could be a clinically important feature for early diagnosis of PHP1A. To date, however, the details have not been documented. With regard to developmental delays, we conducted a multicenter retrospective study of 22 PHP1A patients from 18 families who were diagnosed clinically or genetically from 2005 to 2015. For quantitative analysis of their development, we calculated the ratios of the milestone ages of the patients to those in normal reference data. The ratio of the ages with respect to speech development, i.e., speaking a first meaningful word (median: 1.67), was significantly higher than that for gross motor development, walking unassisted (median: 1.34). The ratio of age at stringing a two-word sentence (median: 1.32) was significantly lower than that of saying a first word (median: 1.84). Ten out of 11 (91%) patients exhibited two or three of the following clinical phenotypes: developmental delay, obesity, and hyperthyrotropinemia. These results suggest two possible clinical features of developmental delays in PHP1A patients: developmental delay is more obvious in speech acquisition than in gross motor skills, and speech delays could be attenuated during later childhood. Further, the presence of multiple of three clinical symptoms could be an important indicator to differentiate the diagnosis of PHP1A during early childhood.

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  • Yuya Tsurutani, Kengo Miyoshi, Kosuke Inoue, Tomoko Takiguchi, Jun Sai ...
    Type: Original
    Article ID: EJ18-0445
    Published: 2019
    [Advance publication] Released: January 22, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Adrenal Cushing’s syndrome (CS) is caused by cortisol-producing adrenal adenoma and is frequently accompanied by glucose metabolism disorders, which are characterized by increased insulin resistance and insufficient β-cell compensation. However, considering the rarity of CS, few studies have assessed whether the glucose metabolism disorders could be ameliorated by surgical treatment. In this case series, we evaluated glucose metabolism before and after surgery in 11 patients (10 women and 1 man) who underwent unilateral adrenalectomy for overt adrenal CS between 2005 and 2016. Patients with pre-diagnosed diabetes mellitus (DM) were excluded. Pre- and post-operative 75-g oral glucose tolerance tests were performed. Cortisol secretion decreased significantly after surgery (median 24-h urinary free cortisol: 582.0 μg/day [interquartile range: 321.0–743.0 μg/day] to 31.3 μg/day [23.6–40.6 μg/day], p = 0.001). The results of the OGTT generally improved after surgery (normal glucose tolerance/impaired glucose tolerance/DM: 2/8/1 to 8/3/0), with significant decreases in the immunoreactive insulin and glucose levels. We also found a decrease in the median homeostatic model assessment of insulin resistance (2.4 [1.4–2.8] to 1.0 [0.6–1.1], p = 0.002), and increases in the median Matsuda index (3.0 [2.3–4.5] to 8.2 [6.3–11.4], p < 0.001), median insulinogenic index (0.70 [0.22–1.51] to 1.22 [0.78–1.64], p = 0.08), and median disposition index (609.1 [237.8–1,095.2] to 1,286.0 [1,034.6–1,857.6], p = 0.002). These findings indicate that adrenalectomy for adrenal CS without overt DM may help ameliorate glucose metabolism disorders, and improve both insulin resistance and insulin secretion.

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  • Yasushi Hirota
    Type: Review
    Article ID: EJ18-0431
    Published: 2019
    [Advance publication] Released: January 08, 2019
    JOURNALS FREE ACCESS ADVANCE PUBLICATION

    Blastocyst implantation contains the following three processes: apposition, attachment, and invasion of the blastocyst. Ovarian hormone progesterone (P4) regulates these processes exquisitely. P4-induced molecular communications between the endometrial epithelium and stroma as well as endometrial proliferation-differentiation switching (PDS) until blastocyst attachment are fundamental steps in blastocyst implantation. Based on the knowledge obtained from the previous studies of mouse models by my group and others, this article outlines how P4 directs the uterus to complete blastocyst implantation.

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  • Nuri Karadurmus, Mehmet Ilkin Naharci, Sinasi Erol Bolu, Aydogan Aydog ...
    Article ID: RET10-1
    Published: 2010
    [Advance publication] Released: November 12, 2010
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    This article released online on September 22, 2010 as advance publication was withdrawn at the request of the authors.
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  • Nuri Karadurmus, Mehmet Ilkin Naharci, Sinasi Erol Bolu, Aydogan Aydog ...
    Article ID: K10E-195
    Published: 2010
    [Advance publication] Released: September 22, 2010
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    This article was retracted. See the Notification.
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  • Chengjiang LI, Mingzhi XU, Qing GU
    Article ID: K08E-187
    Published: 2008
    [Advance publication] Released: November 20, 2008
    JOURNALS FREE ACCESS ADVANCE PUBLICATION
    This article was retracted. See the Notification.
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