著者

Yukio IKEDA Tadashi SUEHIRO Shigeo YAMANAKA Yoshitaka KUMON Hiroshi TAKATA Shojiro INADA Naoko OGAMI Fumiaki OSAKI Mari INOUE Kaoru ARII Kozo HASHIMOTO

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.53, no.5, pp.665-670, 2006 (Released:2006-10-31)

参考文献数

23

被引用文献数

6 10

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The oxidative modification of low-density lipoproteins (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Iron plays a part in the formation of highly toxic free radicals such as hydroxide and superoxide anions, which can induce lipid peroxidation. We investigated whether serum iron status was associated with circulating oxidized LDL (oxLDL) levels in type 2 diabetic patients, in whom oxidative stress and susceptibility to lipid oxidation were supposedly increased. Serum ferritin levels were significantly correlated with plasma oxLDL concentrations in both male and female patients (p<0.02 and p<0.05, respectively). No correlation was detected between ferritin and LDL-cholesterol (LDL-C) concentrations despite the close correlation between LDL-C and oxLDL concentrations (p<0.0001). Stepwise regression analysis showed that ferritin concentration was an independent positive determinant of oxLDL level, in addition to triglyceride concentration, body mass index and sex. This is the first report to show that serum ferritin is associated with circulating oxLDL levels in patients with type 2 diabetes. Further work is required to establish a causative link between iron excess and the development of diabetic vascular complications.

著者

Goro Sasaki Tomohiro Ishii Naoaki Hori Naoko Amano Keiko Homma Seiji Sato Tomonobu Hasegawa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.66, no.9, pp.837-842, 2019 (Released:2019-09-28)

参考文献数

30

被引用文献数

3 11

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Steroid 5α-reductase type 2 deficiency (5αRD2) is a congenital disorder of sex development caused by impairment of conversion from testosterone (T) to 5α-dihydrotestosterone (DHT). DHT deficiency leads to various degrees of undervirilized external genitalia including micropenis, primarily correlated with mutations of the SRD5A2 gene that encodes 5α-reductase type 2. Four Japanese boys with isolated micropenis were diagnosed as 5αRD2 by elevated ratios of serum T/DHT, and decreased ratios of urinary 5α/5β-reduced steroid metabolites. Genetic analyses for SRD5A2 identified that the four patients shared a hypomorphic mutation R227Q that has a residual activity related to the mild-form of 5αRD2. For prepubertal micropenis, DHT was transdermally applied to the four patients at the ages of 4–11 year, increasing a median of stretched penile lengths (SPLs) from 2.6 cm (–2.5 SD) to 4.4 cm (–0.2 SD). Nevertheless, the post-pubertal penile growth was apparently retarded, despite normal levels of T secreted from well-developed testes. The second course of DHT treatment underwent at ages of 12–18 year, but unable to normalize SPLs at a range of 6.0 to 7.0 cm (–3.4 to –2.4 SD). The prostate volumes of two patients were variable at 8.1 and 21 cm3, and a sperm cell count of one patient was normal as young adult. DHT treatment contributes to development of the penis and prostate, which are favorable for the potential fertility of 5αRD2 adults. Meanwhile, the retarded penile growth and a risk of prostate overgrowth may complicate the post-pubertal management with DHT for 5αRD2 males.

著者

Tomohiro Suzuki Mayuko Hayashi Tetsuro Komatsu Akiko Tanioka Masahiro Nagasawa Kyoko Tanimura-Inagaki Mohammad Sharifur Rahman Shinnosuke Masuda Kosuke Yusa Juro Sakai Hiroshi Shibata Takeshi Inagaki

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ21-0255, (Released:2021-07-15)

被引用文献数

2

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α-Ketoglutarate (α-KG) also known as 2-oxoglutarate (2-OG) is an intermediate metabolite in the tricarboxylic acid (TCA) cycle and is also produced by the deamination of glutamate. It is an indispensable cofactor for a series of 2-oxoglutarate-dependent oxygenases including epigenetic modifiers such as ten-eleven translocation DNA demethylases (TETs) and JmjC domain-containing histone demethylases (JMJDs). Since these epigenetic enzymes target genomic DNA and histone in the nucleus, the nuclear concentration of α-KG would affect the levels of transcription by modulating the activity of the epigenetic enzymes. Thus, it is of great interest to measure the nuclear concentration of α-KG to elucidate the regulatory mechanism of these enzymes. Here, we report a novel fluorescence resonance energy transfer (FRET)-based biosensor with multiple nuclear localization signals (NLSs) to measure the nuclear concentration of α-KG. The probe contains the α-KG-binding GAF domain of NifA protein from Azotobacter vinelandii fused with EYFP and ECFP. Treatment of 3T3-L1 preadipocytes expressing this probe with either dimethyl-2-oxoglutarate (dimethyl-2-OG), a cell-permeable 2-OG derivative, or citrate elicited time- and dose-dependent changes in the FRET ratio, proving that this probe functions as an α-KG sensor. Measurement of the nuclear α-KG levels in the 3T3-L1 cells stably expressing the probe during adipocyte differentiation revealed that the nuclear concentration of α-KG increased in the early stage of differentiation and remained high thereafter. Thus, this nuclear-localized α-KG probe is a powerful tool for real-time monitoring of α-KG concentrations with subcellular resolution in living cells and is useful for elucidating the regulatory mechanisms of epigenetic enzymes.

著者

Cyndy Liu Tae Nakano-Tateno Motoyasu Satou Constance Chik Toru Tateno

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ21-0106, (Released:2021-07-10)

被引用文献数

4

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Pituitary adenomas are benign tumours that can cause an individual various clinical manifestations including tumour mass effects and/or the diverse effects of abnormal pituitary hormone secretion. Given the morbidity and limited treatment options for pituitary adenomas, there is a need for better biomarkers and treatment options. One molecule that is of specific interest is the signal transducer and activator of transcription 3 (STAT3), a transcription factor that plays a critical role in mediating cytokine-induced changes in gene expression. In addition, STAT3 controls cell proliferation by regulating mitochondrial activity. Not only does activation of STAT3 play a crucial role in tumorigenesis, including pituitary tumorigenesis, but a number of studies also demonstrate pharmacological STAT3 inhibition as a promising treatment approach for many types of tumours, including pituitary tumours. This review will focus on the role of STAT3 in different pituitary adenomas, in particular, growth hormone-producing adenomas and null cell adenomas. Furthermore, how STAT3 is involved in the cell proliferation and hormone regulation in pituitary adenomas and its potential role as a molecular therapeutic target in pituitary adenomas will be summarized.

著者

Miki Nonaka Nagomi Kurebayashi Takashi Murayama Masami Sugihara Kiyoshi Terawaki Seiji Shiraishi Kanako Miyano Hiroshi Hosoda Shosei Kishida Kenji Kangawa Takashi Sakurai Yasuhito Uezono

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.Suppl., pp.S35-S39, 2017 (Released:2017-06-24)

参考文献数

14

被引用文献数

2 9

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Cancer was considered an incurable disease for many years; however, with the development of anticancer drugs and state-of-the art technologies, it has become curable. Cardiovascular diseases in patients with cancer or induced by cancer chemotherapy have recently become a great concern. Certain anticancer drugs and molecular targeted therapies cause cardiotoxicity, which limit the widespread implementation of cancer treatment and decrease the quality of life in cancer patients significantly. The anthracycline doxorubicin (DOX) causes cardiotoxicity. The cellular mechanism underlying DOX-induced cardiotoxicity include free-radical damage to cardiac myocytes, leading to mitochondrial injury and subsequent death of myocytes. Recently, circulating orexigenic hormones, ghrelin and des-acyl ghrelin, have been reported to inhibit DOX-induced cardiotoxicity. However, little is known about the molecular mechanisms underlying their preventive effects. In the present study, we show the possible mechanisms underlying the effects of ghrelin and des-acyl ghrelin against DOX-induced cardiotoxicity through in vitro and in vivo researches.

著者

Yuko CHIBA Katsuhiko SATOH Satoshi UEDA Nobuo KANAZAWA Yoshiaki TAMURA Toshiyuki HORIUCHI

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.54, no.3, pp.379-383, 2007 (Released:2007-07-19)

参考文献数

21

被引用文献数

14 26

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Psychosomatic symptoms in primary hyperparathyroidism (PHPT) are various and include such conditions as obsessive-compulsive disorder, depression, anxiety, and paranoia. In the elderly the clinical features of the disease are often non-specific and difficult to diagnose. To quantify subjective symptoms of patients with hyperparathyroidism in the elderly, we determined whether these clinical manifestations resolved after surgical parathyroidectomy (PTX) in three PHPT patients over eighty years old. They were diagnosed with hypercalcemia, hypophosphatemia, high PTH concentrations, and osteoporosis. A single parathyroid adenoma was confirmed in each patient by Tc-MIBI scintigram, neck ultrasonography and computed tomographic scanning. PTX was performed in these three patients. Assessments of psychologic symptoms, using the Hamilton Rating Scale for Depression (HAM-D), serum calcium, and intact PTH were obtained before and after PTX. Mean weight of the resected adenomas was 438 ± 138 mg (mean ± SD). After PTX, serum calcium decreased from 11.1 ± 0.5 to 9.2 ± 0.5 mg/dl and intact PTH from 160.0 ± 25.2 to 45.3 ± 22.2 pg/ml. Total HAM-D scores in each patient decreased from 45 to 9, 17 to 1 and 15 to 5, respectively. Especially, there were marked improvements in depressive mood, psychomotor inhibition, anxiety and somatic symptoms after PTX. The quality of life in those patients was also improved by PTX. We propose here that PTX in elderly PHPT patients with psychiatric symptoms should be considered instead of oral administration, such as anti-depressants or bisphosphonates.

著者

NOBUYUKI AMINO HISATO TADA YOH HIDAKA KAZUO HASHIMOTO

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.49, no.4, pp.393-397, 2002 (Released:2003-08-29)

参考文献数

8

被引用文献数

8 16

著者

Tezcan Sezgin Muhammet İrfan Dönmez Aylin Dirican İsa Deniz Bülent Savut

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ18-0578, (Released:2019-03-28)

被引用文献数

1

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Partial androgen insensitivity syndrome (PAIS) is a form of disorders of sexual development. Besides the issues of gender assignment, the fate of gonads in these patients poses a challenging problem. Debate still remains on the need and/or timing of gonadectomy in either complete or partial androgen insensitivity syndromes. In this case report, we present a 68-year-old patient who was raised as a woman, stayed married for 45 years and admitted to our endocrinology department with complaint of male type hair distribution after initial examination following move to a nursing home. Physical examination revealed no breast development, a phallus of 6 cm, labia majoras that include testes and a blind ending vagina. Chromosomal analysis confirmed 46,XY with intact SRY and AZF regions. Pelvic ultrasonography and magnetic resonance imaging results indicated testicular tissue in labia majoras in addition to a rudimentary prostate. Gonadectomy was not offered to the patient due to lacking evidence of benefit in this age group and considering possible hormonal side effects. Our patient might be the oldest patient to be diagnosed with PAIS. Treatment and follow-up protocols for adults with PAIS are not standardized and therefore these patients should be individually evaluated and treated. Risks and benefits of surgery should be kept in mind when suggesting gonadectomy.

著者

Yuji Mizuno Eisaku Harada Daisuke Katoh Yusuke Kashiwagi Yoshinobu Morikawa Hitoshi Nakagawa Michihiro Yoshimura Yoshihiko Saito Hirofumi Yasue

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.60, no.1, pp.87-95, 2013 (Released:2013-01-31)

参考文献数

46

被引用文献数

16 27

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B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, PPPPPPP=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.

著者

Yumi Kim Sehee Kim Chanyang Kim Takahiro Sato Masayasu Kojima Seungjoon Park

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0436, (Released:2014-12-23)

被引用文献数

13 37

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Neurogenesis occurs in the adult hippocampus and is enhanced by dietary restriction (DR), and neurogenesis enhancement is paralleled by circulating ghrelin level enhancement. We have previously reported that ghrelin modulates adult neurogenesis in the hippocampus. In order to investigate the possible role of ghrelin in DR-induced hippocampal neurogenesis in adult mice, ghrelin knockout (GKO) mice and wild-type (WT) mice were maintained for 3 months on DR or ad libitum (AL) diets. Protein levels of ghrelin in the stomach and the hippocampus were increased by DR in WT mice. One day after BrdU administration, the number of BrdU-labeled cells in the hippocampal dentate gyrus was decreased in GKO mice maintained on the AL diet. DR failed to alter the proliferation of progenitor cells in both WT and GKO mice. Four weeks after BrdU injection, the number of surviving cells in the dentate gyrus was decreased in AL-fed GKO mice. DR increased survival of newborn cells in WT mice, but not in GKO mice. Levels of brain-derived neurotrophic factor protein in the hippocampus were similar between WT and GKO mice, and were increased by DR both in WT and GKO mice. These results suggest that elevated levels of ghrelin during DR may have an important role in the enhancement of neurogenesis induced by DR.

著者

Yinhua Ni Tao Wu Luna Yang Yang Xu Tsuguhito Ota Zhengwei Fu

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0500, (Released:2018-03-10)

被引用文献数

19

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Oxidative stress caused free radical and mitochondrial damage plays a critical role in the progression of aging and age-related damage at the cellular and tissue levels. Antioxidant supplementation has received growing attention and the effects of antioxidant on aging are increasingly assessed in both animal and human studies. However, additional and more promising treatments that contribute to the expansion of anti-aging therapies are needed. Astaxanthin, a super antioxidant carotenoid and free radical scavenger, inhibits lipid peroxidation more potently than vitamin E. In the present study, we investigated the preventative effects of astaxanthin on aging using an accelerated aging model: mice chronically treated with a combination of D-galactose and jet lag. After 6 weeks of treatment, astaxanthin administration tended to protect the liver weight loss in aged mice. It is probably by upregulating the mRNA expression of galactose-1-phosphate uridyltransferase, which contribute to the enhancement of D-galactose metabolism. Astaxanthin supplementation also improved muscle endurance of aged mice in a swimming test. These results were associated with reduced oxidative stress in serum and increased anti-oxidative enzymes activities and mRNA expression in vivo. Moreover, astaxanthin reversed the dysregulation of aging-related gene expression caused by the combination of D-galactose and jet lag in the liver and kidney of mice. In conclusion, astaxanthin prevents liver weight loss, ameliorates locomotive muscular function, exerts significant anti-aging effects by reducing oxidative stress and improving the expression of age-related genes in D-galactose and jet lag-induced aging model.

著者

Yasuhiro Ito Akira Miyauchi Mitsuyoshi Hirokawa Masatoshi Yamamoto Hitomi Oda Hiroo Masuoka Hisanori Sasai Mitsuhiro Fukushima Takuya Higashiyama Minoru Kihara Akihiro Miya

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0524, (Released:2018-04-04)

被引用文献数

9

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Follicular thyroid carcinoma (FTC), a form of differentiated thyroid carcinoma, is the second most common malignancy arising from thyroid follicular cells. Recently, the tumor-node-metastasis (TNM) classification for differentiated thyroid carcinoma was revised from the 7th to the 8th edition. The diagnostic criteria for poorly differentiated carcinoma (PDC) were also updated in the latest World Health Organization (WHO) classification. In this study, we investigated whether these changes are appropriate for accurately predicting prognosis. Three hundred and twenty-nine patients diagnosed with postoperative pathologically confirmed FTC, who underwent initial surgery at our hospital between 1984 and 2004, were enrolled. For this study, patients were re-evaluated and diagnosed with FTC (N = 285) or PDC (N = 44) without typical nuclear findings of papillary thyroid carcinoma. For FTC, the 8th TNM classification was a more accurate predictor of prognosis than the 7th TNM classification. In the 8th TNM classification, cause-specific survival became significantly poorer from Stage I to IVB. The cause-specific survival of PDC based on the latest WHO classification was worse than, but did not significantly differ from, that of PDC based only on the former WHO classification. For PDC, neither of the TNM classifications could accurately predict prognosis. Taken together, we conclude that (1) the 8th TNM classification more accurately reflects the prognosis of FTC than the 7th TNM classification; (2) PDC based on the former WHO classification should be retained, at least in Japan; and (3) the TNM classification may not be suitable for predicting the prognosis of PDC.

著者

Toshihiko Yanase Ikumi Yanagita Kazuo Muta Hajime Nawata

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ17-0390, (Released:2017-12-14)

被引用文献数

92

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Frailty is a state of vulnerability and a consequence of cumulative decline in multiple physiological systems over a lifespan. The occurrence of frailty depends on deterioration in muscle and nerve function, declining cardiopulmonary reserve and loss of executive function. Diabetes mellitus (DM) often causes functional impairment in each of the above systems, thus leading to a loss of whole body homeostasis and deterioration in physical function. Inability of self-management in DM patients may also have considerable impact on the development of sarcopenia/frailty. Thus, there may be positive feedback between the progression of diabetic complications and frailty/sarcopenia. While various factors are involved in this process, insulin resistance or insulin depletion may be an important factor in the progression of frailty in diabetes patients since insulin is well known to be an anabolic hormone in muscle. Interestingly, in our study targeting elderly DM patients, low HbA1c was a significant and independent risk factor for frailty, as assessed using a broad sense frailty scale, the Clinical Frailty Scale (CSF), suggesting that reverse metabolism due to malnutrition in elderly type 2 DM patients might be involved. Therefore, an intervention that includes proper nutrition and exercise training may be essential for the prevention of frailty. The pathogenesis of frailty in DM patients is extensively discussed in this review.

著者

Wataru Ogawa Yushi Hirota Shigeru Miyazaki Tadashi Nakamura Yoshihiro Ogawa Iichiro Shimomura Toshimasa Yamauchi Koutaro Yokote on behalf of the Creation Committee for Guidelines for the Management of Obesity Disease 2022 by Japan Society for the Study of Obesity (JASSO)

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ23-0593, (Released:2023-12-20)

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To identify those who might benefit from weight reduction within a large population of obese individuals, Japan Society for the Study of Obesity (JASSO) advocated the concept of “obesity disease.” Here we summarize the definition, criteria, and core concepts for the management of obesity disease based on JASSO’s latest guideline. JASSO defines obesity as excessive fat storage in adipose tissue associated with a BMI of ≥25 kg/m2. The threshold BMI of obesity is low as compared to Western countries given that Japanese individuals tend to develop obesity-related health disorders at lower BMI. Obesity with a BMI of ≥35 kg/m2 is referred to as “high-degree obesity” as treatment strategies vary based on the degree of obesity. Obesity is diagnosed as “obesity disease” if accompanied by any of the 11 specific obesity-related health disorders that weight reduction can prevent or alleviate, or if it meets the criteria for visceral fat obesity with a visceral fat area of ≥100 cm2. The initial weight reduction goals for high-degree obesity disease range from 5% to 10% of their current body weight, depending on the associated health disorders. That for those with obesity disease who do not qualify as high-degree is 3% or more. If these initial goals are not achieved, intensifying dietary therapy or introducing drug therapy (or both) may be necessary. While surgical treatment is primarily indicated for high-degree obesity disease, it might be appropriate for cases of obesity disease with a BMI <35 kg/m2, depending on the accompanying health disorders. Enhancing the quality of life for individuals with obesity or obesity disease necessitates a broader societal approach, emphasizing the resolution of related stigma.

著者

Natsuko Watanabe Jaeduk Yoshimura Noh Ai Kozaki Ran Yoshimura Ai Yoshihara Nami Suzuki Masako Matsumoto Miho Fukushita Aya Kinoshita Azusa Aida Hideyuki Imai Shigenori Hiruma Toshu Inoue Kosuke Inoue Kiminori Sugino Koichi Ito

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.70, no.11, pp.1087-1096, 2023 (Released:2023-11-28)

参考文献数

40

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Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves’ orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves’ disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16–1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15–1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96–4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

著者

Chong-gui Zhu Ya-xin Liu Hao Wang Bao-ping Wang Hui-qi Qu Bao-li Wang Mei Zhu

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.7, pp.663-673, 2017 (Released:2017-07-28)

参考文献数

35

被引用文献数

35 40

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The purpose of this study was to determine whether treatment using the active form of vitamin D (1,25(OH)2D3) could protect against high-fat diet (HFD)-induced non-alcoholic fatty liver disease (NAFLD) in rats and ameliorate oxidative stress. Male Sprague-Dawley rats were divided into three groups and treated with standard chow, HFD, or HFD plus intraperitoneal injection of 1,25(OH)2D3 (5 μg/kg body weight, twice per week), respectively, for 16 weeks. Serum lipid profiles, hepatic function, intrahepatic lipid, and calcium levels were determined. Hepatic histology was examined using hematoxylin/eosin, Masson’s trichrome, and Oil Red O staining. Oxidative stress was assessed by measuring hepatic malondialdehyde (MDA) and F2α-isoprostane content. Expression of nuclear factor-erythroid-2-related factor 2 (Nrf2) and downstream target genes was analyzed using quantitative RT-PCR. 1,25(OH)2D3 treatment improved the serum lipid profile, reduced intrahepatic lipid levels, and attenuated hepatic steatosis and inflammation in HFD rats. Furthermore, MDA and F2α-isoprostane levels in liver tissue were reduced by 1,25(OH)2D3 administration. Although 1,25(OH)2D3 did not regulate the expression of Nrf2 mRNA, it did induce Nrf2 nuclear translocation. The expression of Nrf2 target genes, including Gclc, Nqo1, Sod2, and Cat, was up-regulated by 1,25(OH)2D3. We conclude that 1,25(OH)2D3 protects against HFD-induced NAFLD by attenuating oxidative stress, inducing NRF2 nuclear translocation, and up-regulating the expression of genes encoding antioxidant enzymes.

著者

Sha Ye Yepei Huang Yi Lu Xiaoyan Li Meiling Ye Hongyu Lu Junhua Shi Jian Huang Hong Cai

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ23-0451, (Released:2023-11-17)

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This study explored a more precise association between androgens and glycolipid metabolism in healthy women of different ages. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio were used as body fat indicators. High-density lipoprotein (HDL), low-density lipoprotein, triglycerides, and total cholesterol were used as lipid markers. Fasting blood glucose (FBG), fasting insulin, and the homeostatic model assessment of insulin resistance were used to assess insulin resistance and glucose metabolism. Liquid chromatography-tandem mass spectrometry was used to measure androgen indicators, including testosterone, sex hormone-binding globulin (SHBG), free testosterone (FT), dihydrotestosterone (DHT), androstenedione (A4), dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEAS). DHEAS levels varied across age groups. Correlation analyses with Spearman’s coefficient showed that the free androgen index correlated positively with WC (p = 0.040), FT correlated positively with BMI (p = 0.033) and WC (p = 0.049), SHBG correlated positively with HDL (p = 0.013), and A4 correlated positively with FBG (p = 0.017). Multiple linear regression analysis showed that among healthful women aged 36–40 years, A4 increased with FBG, and SHBG increased with HDL. Even within healthy, nonobese women, lipid and glucose metabolism were robustly correlated with androgens. Yearly metabolic assessments are necessary, particularly for FBG and HDL, since these markers can predict the likelihood of hyperandrogenemia, enabling timely interventions.

著者

Caiyan Mo Liyong Zhong

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ23-0356, (Released:2023-10-25)

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Long-term stimulation of thyroid follicular epithelium by high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in patients with acromegaly can lead to thyroid dysfunction, goiter, thyroid nodules, and even thyroid cancer and thyroid-associated ophthalmopathy (TAO). Excessive GH/IGF-1 promotes goiter and thyroid nodule formation, which can be reversed by normalizing the IGF-1 levels with surgery or medical treatment. Whether patients with acromegaly have an increased risk of thyroid cancer remains controversial, and routine thyroid ultrasonography and regular cancer screening are recommended in such cases, especially when the nodules possess malignant propensity. TAO is an autoimmune disease and newer treatments are being discovered against it. Recent studies have reported that the IGF-1 receptor (IGF-1R) plays an important role in the pathogenesis of TAO, and the IGF-1R inhibitor teprotumumab involves significantly improved disease endpoints in patients with active TAO. Thyroid-stimulating hormone (TSH) receptor (TSHR) and IGF-1R co-immunoprecipitate in orbital and thyroid tissues to form a functional complex; thus, combined therapy targeting TSHR and IGF-1R may be more effective than single therapy.

著者

Kai Yoshimura Masaaki Yamamoto Tomoya Inoue Hidenori Fukuoka Keiji Iida Wataru Ogawa

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.69, no.11, pp.1335-1342, 2022 (Released:2022-11-28)

参考文献数

54

被引用文献数

1 8

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Coronavirus disease 2019 (COVID-19) is associated with endocrine disorders, but their long-term clinical course remains unclear. We here report the 15-month clinical course for an individual with multiple endocrine disorders of the pituitary gland and testis likely triggered by COVID-19. A 65-year-old man with no history of endocrinopathy was admitted for acute COVID-19 pneumonia. Although his respiratory condition improved after administration of antiviral drugs, his blood pressure dropped suddenly to a preshock level and was refractory to vasopressors. The circulating adrenocorticotropic hormone (ACTH) and cortisol concentrations were low, and secondary adrenal insufficiency was suspected. Administration of hydrocortisone rapidly ameliorated the hypotension, and the patient was discharged taking 15 mg of hydrocortisone daily. An insulin tolerance test performed 3 months later revealed impaired ACTH, cortisol, and growth hormone (GH) responses, indicative of combined hypopituitarism. The patient also manifested symptoms of hypogonadism, and a hormonal workup suggested primary hypogonadism. At 12 months after discharge, GH and ACTH responses had recovered completely and partially, respectively. After another 3 months, basal ACTH and cortisol levels had been restored to the normal range and the patient discontinued hydrocortisone replacement without exacerbation of symptoms, although his hypogonadism persisted. The patient thus developed transient GH and ACTH deficiency that lasted for more than a year as well as persistent primary hypogonadism during intensive care for COVID-19. Certain prolonged symptoms of COVID-19 might be accounted for by such hormonal disturbance.

著者

Kumiko Hamano Hiroshi Nishiyama Akiko Matsui Manaka Sato Masakazu Takeuchi

出版者

The Japan Endocrine Society

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.64, no.4, pp.449-456, 2017 (Released:2017-04-29)

参考文献数

24

被引用文献数

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In 855 Japanese patients with type 2 diabetes receiving once weekly dulaglutide 0.75 mg in 3 phase 3 studies, the effects on efficacy and safety at week 26 (last observation carried forward) were investigated in a post hoc descriptive analysis of subgroups of age (<65 years [young], ≥65 years [elderly]) and body mass index (BMI [<25 kg/m2, ≥25 kg/m2]). The 4 subgroups were as follows: 1) the young/low-BMI subgroup (Y/L) (n = 255); 2) the young/high-BMI subgroup (Y/H) (n = 386), 3) the elderly/low-BMI subgroup (E/L) (n = 137), and 4) the elderly/high-BMI subgroup (E/H) (n = 77). The mean changes from baseline in glycated hemoglobin (HbA1c) and body weight, respectively, were -1.69% and -0.29 kg in the Y/L subgroup; -1.48% and -0.09 kg in the Y/H subgroup; -1.68% and -0.20 kg in the E/L subgroup; and -1.72% and -0.26 kg in the E/H subgroup. The incidences of nausea and hypoglycemia, respectively, were 6.7% and 11.0% in the Y/L subgroup; 7.0% and 8.0% in the Y/H subgroup; 10.2% and 18.2% in the E/L subgroup; and 3.9% and 22.1% in the E/H subgroup. Dulaglutide improved HbA1c regardless of age or BMI; a higher incidence of hypoglycemia was observed in elderly patients compared to younger patients.