著者

Katsumi IIZUKA Yukio HORIKAWA

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.55, no.4, pp.617-624, 2008 (Released:2008-08-27)

参考文献数

46

被引用文献数

62 158

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Excess carbohydrate intake leads to fat accumulation and insulin resistance. Glucose and insulin coordinately regulate de novo lipogenesis from glucose in the liver, and insulin activates several transcription factors including SREBP1c and LXR, while those activated by glucose remain unknown. Recently, a carbohydrate response element binding protein (ChREBP), which binds to the carbohydrate response element (ChoRE) in the promoter of rat liver type pyruvate kinase (LPK), has been identified. The target genes of ChREBP are involved in glycolysis, lipogenesis, and gluconeogenesis. Although the regulation of ChREBP remains unknown in detail, the transactivity of ChREBP is partly regulated by a phosphorylation/dephosphorylation mechanism. During fasting, protein kinase A and AMP-activated protein kinase phosphorylate ChREBP and inactivate its transactivity. During feeding, xylulose-5-phosphate in the hexose monophosphate pathway activates protein phosphatase 2A, which dephosphorylates ChREBP and activates its transactivity. ChREBP controls 50% of hepatic lipogenesis by regulating glycolytic and lipogenic gene expression. In ChREBP -/- mice, liver triglyceride content is decreased and liver glycogen content is increased compared to wild-type mice. These results indicate that ChREBP can regulate metabolic gene expression to convert excess carbohydrate into triglyceride rather than glycogen. Furthermore, complete inhibition of ChREBP in ob/ob mice reduces the effects of the metabolic syndrome such as obesity, fatty liver, and glucose intolerance. Thus, further clarification of the physiological role of ChREBP may be useful in developing treatments for the metabolic syndrome.

著者

Masato Kotani Fumihiko Katagiri Tsuyoshi Hirai Jiro Kagawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.11, pp.1137-1140, 2014 (Released:2014-11-28)

参考文献数

14

被引用文献数

2 14

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The hypothalamic hormone kisspeptin (metastin) regulates human reproduction by modulating gonadotropin-releasing hormone (GnRH) secretion. Kisspeptin is detected in peripheral blood, although GnRH is not. In this study, we measured plasma kisspeptin levels in four male cases with hypogonadism and seven normal male controls using enzyme immunoassay (EIA) to elucidate the clinical implications of kisspeptin levels in male hypogonadism. The results showed a variety of plasma kisspeptin levels: 6.0 fmol/mL in a male with isolated hypogonadotropic hypogonadism (IHH), 43.2 fmol/mL in a male with Kallmann’s syndrome, 40.7 fmol/mL in a male with azoospermia, 323.2 fmol/mL in a male with hypergonadotropic hypogonadism, and 12.3 ± 2.5 fmol/mL (mean ± SD) in seven normal controls. Except for the case with IHH, the plasma kisspetin levels were elevated in the three cases with Kallmann’s syndrome, azoospermia, and hypergonadotropic hypogonadism. The reason why the three cases had high values was their lesions were downstream of the kisspeptin neuron in the hypothalamic-pituitary-gonadal axis, suggesting that elevated kisspeptin levels were implicated in hypothalamic kisspeptin secretion under decreased negative feedback of gonadal steroids. The result that the plasma kisspeptin levels were decreased by gonadotropin therapy in the case with Kallmann’s syndrome supported this hypothesis. In conclusion, to measure plasma kisspeptin levels could be useful for better understanding of male hypogonadism.

著者

Makito Tanabe Yuko Akehi Takashi Nomiyama Junji Murakami Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0313, (Released:2014-10-23)

被引用文献数

2 21

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Endogenous testosterone is known to be protective against metabolic syndrome (MetS) in men. While various markers of testosterone status including serum total testosterone (TT), free testosterone (measured using analogue ligand RIA [aFT]), calculated FT (cFT), calculated bioavailable T (cbT), and sex-hormone binding globulin (SHBG) are recognized, it is unclear which of these markers are the most appropriate ones for the detection of MetS. We measured various testosterone values and metabolic markers in 249 healthy Japanese males (mean age 52.7 ± 7.4 yr) and analyzed which testosterone value is most associated with various metabolic parameters, including MetS as diagnosed according to the International Diabetes Federation (IDF, 2009 version) or with the Japanese criteria. Age had no effect on the TT level but significantly decreased aFT, cFT, and cbT levels and significantly increased the SHBG level. All testosterone values and SHBG showed weak inverse relationships with the metabolic markers BMI, waist circumference, insulin, HOMA-R, and HOMA-β, with the strongest relationship being to TT. TT and SHBG were significantly lower in men with MetS than in men without MetS. All testosterone values gradually decreased as the number of MetS components increased. Multivariate analysis revealed that the TT median value of <4.0 ng/mL was the only significant marker for the detection of MetS. These results were essentially the same regardless of whether the diagnosis of MetS was based on the IDF or the Japanese criteria. In conclusion, among various testosterone values, TT is the most reliable indicator of MetS in middle-aged Japanese men.

著者

Yasuhiro Ito Akira Miyauchi Minoru Kihara Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0138, (Released:2014-04-17)

被引用文献数

6 30

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In papillary thyroid carcinoma (PTC), macroscopic extrathyroid extension (Ex) and clinical node metastasis (N) are prominent prognostic factors. Ex is divided into two grades in the UICC TNM classification: minimal and massive Ex. Massive Ex significantly affects patients’ prognoses, whereas minimal Ex has little prognostic value. N is also divided into two grades in the TNM classification: N1a and N1b, depending on the location of metastasis, with N1b graded higher than N1a. However, massive Ex and/or N-positive PTC includes patients with a wide range of biological characteristics and prognoses, depending on their degrees of Ex and N. Other clinicopathological features such as age, gender, and tumor size also influence the prognosis. In evaluations of the biological characteristics of PTC patients with Ex and/or N, we should consider the degrees and relationships of _Ex and N _ with other clinicopathological features.

著者

Shinya Furukawa Shin Yamamoto Yasuhiko Todo Kotatsu Maruyama Teruki Miyake Teruhisa Ueda Tetsuji Niiya Takatoshi Senba Masamoto Torisu Teru Kumagi Syozo Miyauchi Takenori Sakai Hisaka Minami Hiroaki Miyaoka Bunzo Matsuura Yoichi Hiasa Morikazu Onji Takeshi Tanigawa

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0206, (Released:2014-08-07)

被引用文献数

10 44

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Subclinical hypothyroidism (SCH) has been associated with type 2 diabetes mellitus. However, it is unknown whether common complications of type 2 diabetes, such as diabetic nephropathy, are also present with SCH. Here, we investigated the association between SCH and diabetic nephropathy among Japanese patients with type 2 diabetes mellitus. In this multicenter cross-sectional study, we recruited 414 such patients who had no previous history of thyroid disease. Serum thyroid hormone levels and the urinary albumin:creatinine ratio were measured. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.0 mIU/L), and diabetic nephropathy was defined as creatinine levels ≥300 mg/g. The prevalence of SCH was 8.7% (n = 36) among patients with type 2 diabetes mellitus. The SCH group had a higher prevalence of dyslipidemia (p = 0.008) and diabetic nephropathy (p = 0.014) than the euthyroid group. Multivariate analysis identified significant positive associations between diabetic nephropathy and SCH (odds ratio [OR], 3.51; 95% confidence interval [CI], 1.10-10.0; p = 0.034), hypertension (OR, 4.56; 95% CI, 1.69-14.7; p = 0.001), and smoking (OR, 3.02; 95% CI, 1.14-7.91; p = 0.026). SCH may be independently associated with diabetic nephropathy in Japanese patients with type 2 diabetes mellitus.

著者

Atsushi Yoshikawa Akihisa Imagawa Shinsuke Nakata Kenji Fukui Yohei Kuroda Yugo Miyata Yoshifumi Sato Toshiaki Hanafusa Taka-aki Matsuoka Hideaki Kaneto Hiromi Iwahashi Iichiro Shimomura

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ14-0219, (Released:2014-07-15)

被引用文献数

1

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Type 1 diabetes, one of two major forms of diabetes, results from the complete destruction of pancreatic beta cells. Viral infection has been suggested to be a trigger of beta cell destruction, the pathogenesis of type 1 diabetes. The aim of this study was to clarify the role of the protein encoded by intherferon stimulated gene (ISG) 15, an antiviral effector, in the development of this clinical entity. We used the mouse beta cell line MIN6 to investigate the role of ISG15 and paid special attention to apoptosis. Although not detected in native MIN6 cells, free ISG15 and ISG15 conjugated proteins were both present in dose-dependently increased amounts following stimulation with interferon alpha. As assessed both by caspase 3/7 activity and an annexin V assay, the percentage of apoptotic MIN6 cells (after exposure to the inflammatory cytokines of interleukin-1beta plus interferon gamma or tumor necrosis factor alpha) was decreased by pretreatment with adenovirus-expressing ISG15 and increased by expressing a short hairpin RNA directed against ISG15. In conclusion, ISG15 has an anti-apoptotic effect on MIN6 cells. Thus, promoting ISG15 expression in the pancreatic beta cells could be a potential therapeutic approach for patients with type 1 diabetes.

著者

Yasuhiro Ito Akira Miyauchi Minoru Kihara Takuya Higashiyama Kaoru Kobayashi Akihiro Miya

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.5, pp.491-497, 2014 (Released:2014-05-31)

参考文献数

12

被引用文献数

5 17

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Among the several prognostic factors of papillary thyroid carcinoma (PTC), age is the most prominent. It is well known that elderly PTC patients have poorer prognoses. Here we investigated the prognostic impact of young age in univariate and multivariate analyses. We retrospectively analyzed 5,733 PTC patients without distant metastasis at presentation, who underwent initial surgery at Kuma Hospital. The median follow-up period was 150 months. We classified the patients into three groups: young (< 30 years), middle-aged (30−59), and older patients (≥ 60 years). The tumor size was larger and clinical node positivity was higher in the young patients, and significant extrathyroid extension was higher in the older patients compared to the other two groups. In the univariate analysis, the young patients showed poorer extrathyroidal locoregional and distant recurrence rates than the middle-aged patients, but not cause-specific survival rates. In the multivariate analysis, age < 30 years was an independent or marginal predictor of extrathyroidal locoregional and distant recurrence, but not of carcinoma-related death. Age ≥ 60 years independently affected PTC recurrence and death. Taken together, we should carefully treat young PTC patients because of the likeliness of extrathyroidal locoregional and distant recurrence, which may not be life-threatening.

著者

Mika Shimamura Yuji Nagayama Michiko Matsuse Shunichi Yamashita Norisato Mitsutake

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.5, pp.481-490, 2014 (Released:2014-05-31)

参考文献数

44

被引用文献数

8 38

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Cancer stem-like cells (CSCs) play important roles in cancer initiation and progression. CSCs have been isolated using several markers, but those for thyroid CSCs remain to be confirmed. We therefore conducted a comprehensive search for thyroid CSC markers. Expression of nine cell surface markers (CD13, CD15, CD24, CD44, CD90, CD117, CD133, CD166, and CD326) and aldehyde dehydrogenase (ALDH) activity, which are CSC markers in various solid cancers, and the ability to form spheres in vitro and tumors in vivo were investigated using eight thyroid cancer cell lines (FRO, KTC1/2/3, TPC1, WRO, ACT1, and 8505C). Among these, four cell lines (FRO, KTC3, ACT1, and 8505C) possessed the both abilities; however, common markers indicative of CSCs were not observed. The pattern of ability to form spheres was completely matched to that of tumor formation, suggesting that our sphere assay is valuable for assessment of tumor-forming ability. Next, the cells were sorted using these markers and subjected to the sphere assay. In three cell lines (FRO, KTC3, and ACT1), ALDHpos cells showed higher sphere forming ability than ALDHneg cells but not in other cells. CD326hi also appeared to be a candidate marker only in FRO cells. However, these subpopulations did not follow a classical hierarchical model because ALDHneg and CD326low fractions also generated ALDHpos and CD326hi cells, respectively. These data suggest that ALDH activity is probably a major candidate marker to enrich thyroid CSCs but not universal; other markers such as CD326 that regulate different CSC properties may exist.

著者

Toru Takano

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0517, (Released:2014-01-22)

被引用文献数

5 30

---

Thyroid cancer cells were believed to be generated by multi-step carcinogenesis, in which cancer cells are derived from thyrocytes, via multiple incidences of damage to their genome, especially in oncogenes or anti-oncogenes that accelerate proliferation or foster malignant phenotypes, such as the ability to invade the surrounding tissue or metastasize to distant organs, until a new hypothesis, fetal cell carcinogenesis, was presented. In fetal cell carcinogenesis, thyroid tumor cells are assumed to be derived from three types of fetal thyroid cell which only exist in fetuses or young children, namely, thyroid stem cells (TSCs), thyroblasts and prothyrocytes, by proliferation without differentiation. Genomic alternations, such as RET/PTC and PAX8-PPARgamma1 rearrangements and a mutation in the BRAF gene, play an oncogenic role by preventing thyroid fetal cells from differentiating. Fetal cell carcinogenesis effectively explains recent molecular and clinical evidence regarding thyroid cancer, including thyroid cancer initiating cells (TCICs), and it underscores the importance of identifying a stem cells and clarifying the molecular mechanism of organ development in cancer research. It introduces three important concepts, the reverse approach, stem cell crisis and mature and immature cancers. Further, it implies that analysis of a small population of cells in a cancer tissue will be a key technique in establishing future laboratory tests. In the contrary, mass analysis such as gene expression profiling, whole genomic scan, and proteomics analysis may have definite limitations since they can only provide information based on many cells.

著者

Nisha Balmiki Biswabandhu Bankura Srikanta Guria Tapas Kumar Das Arup Kumar Pattanayak Anirban Sinha Sudipta Chakrabarti Subhankar Chowdhury Madhusudan Das

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.61, no.3, pp.289-296, 2014 (Released:2014-03-30)

参考文献数

31

被引用文献数

1 15

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Recent research has revealed that genetic defects due to mutation in the Thyroid Peroxidase (TPO ) gene can lead to thyroid dysfunction in the population. We aimed to study the association between genetic defects in TPO gene and patients with hypothyroidism found in adult age. Two hundred consecutive treatment naive hypothyroid patients (age ≥ 18 years) (cases) who were negative for anti TPO antibody and their corresponding sex and age matched two hundred normal individuals (controls) were enrolled. The 17 exonic regions of the TPO gene were amplified and sequenced directly. We identified 6 different previously known single nucleotide polymorphisms (SNPs) and 2 novel deletions in TPO gene. Two of the six SNPs revealed a significant association with hypothyroidism; Thr725Pro (rs732609) and Asp666Asp (rs1126797). The c.2173C allele of the Thr725Pro in TPO showed a significant association among hypothyroid patients compared to controls (p = 0.01; Odds ratio=1.45; 95% CI: 1.09-1.92) suggesting it to be a potential risk allele toward disease predisposition. Analysis of genotype frequencies of the polymorphism between the two groups demonstrated CC as a potential risk genotype (p = 0.006; Odds ratio=1.95; 95% CI: 1.2-3.15) for the disease while another SNP Asp666Asp (c.1998T allele) showed protectiveness towards the disease (p = 0.006; Odds ratio = 0.67; 95%CI: 0.50-0.89). To our knowledge, this is first study reporting the role of TPO gene with hypothyroidism in a population of Asian Indian origin. The study threw up the possibility of TPO gene polymorphisms as a possible pathogenetic mechanism of hypothyroidism.

著者

Mika Shimamura Yuji Nagayama Michiko Matsuse Shunichi Yamashita Norisato Mitsutake

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0526, (Released:2014-02-15)

被引用文献数

8 38

---

Cancer stem-like cells (CSCs) play important roles in cancer initiation and progression. CSCs have been isolated using several markers, but those for thyroid CSCs remain to be confirmed. We therefore conducted a comprehensive search for thyroid CSC markers. Expression of nine cell surface markers (CD13, CD15, CD24, CD44, CD90, CD117, CD133, CD166, and CD326) and ALDH activity, which are CSC markers in various solid cancers, and the ability to form spheres in vitro and tumors in vivo were investigated using eight thyroid cancer cell lines (FRO, KTC1/2/3, TPC1, WRO, ACT1, and 8505C). Among these, four cell lines (FRO, KTC3, ACT1, and 8505C) possessed the both abilities; however, common markers indicative of CSCs were not observed. The pattern of ability to form spheres was completely matched to that of tumor formation, suggesting that our sphere assay is valuable for assessment of tumor-forming ability. Next, the cells were sorted using these markers and subjected to the sphere assay. In three cell lines (FRO, KTC3, and ACT1), ALDHpos cells showed higher sphere forming ability than ALDHneg cells but not in other cells. CD326hi also appeared to be a candidate marker only in FRO cells. However, these subpopulations did not follow a classical hierarchical model because ALDHneg and CD326low fractions also generated ALDHpos and CD326hi cells, respectively. These data suggest that ALDH activity is probably a major candidate marker to enrich thyroid CSCs but not universal; other markers such as CD326 that regulate different CSC properties may exist.

著者

Yoshifumi Saisho Kumiko Tanaka Takayuki Abe Toshihide Kawai Hiroshi Itoh

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0376, (Released:2013-11-09)

被引用文献数

7 17

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The aim of this study was to clarify the relationship between baseline beta cell function and future glycated albumin (GA) to glycated hemoglobin ratio (GA/HbA1c) in patients with type 2 diabetes. In our retrospective cohort, 210 type 2 diabetic patients who had been admitted to our hospital and in whom HbA1c and GA had been measured at baseline and 2 years after admission were included in this study. Baseline beta cell function was assessed by postprandial C-peptide immunoreactivity index (PCPRI) during admission. With intensification of treatment during admission, HbA1c and GA were significantly decreased 1 year and 2 years after admission. While baseline HbA1c was not significantly correlated with HbA1c after 2 years, baseline GA/HbA1c was strongly correlated with GA/HbA1c after 2 years (r = 0.575, P <0.001). When the patients were divided into two groups according to median PCPRI, patients with low PCPRI showed higher GA/HbA1c both at baseline and after 2 years compared to those with high PCPRI. There was a significant negative correlation between PCPRI and GA/HbA1c after 2 years (r = -0.379, P <0.001). Multiple regression analysis revealed that PCPRI was an independent predictor of GA/HbA1c after 2 years. In conclusion, our findings suggest that lower beta cell function is associated with sustained higher GA/HbA1c ratio in patients with type 2 diabetes.

著者

Aya Nakamura Masami Watanabe Morito Sugimoto Tomoko Sako Sabina Mahmood Haruki Kaku Yasutomo Nasu Kazushi Ishii Atsushi Nagai Hiromi Kumon

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.60, no.3, pp.275-281, 2013 (Released:2013-03-31)

参考文献数

11

被引用文献数

7 73

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Gender identity disorder (GID) is a conflict between a person’s actual physical gender and the one they identify him or herself with. Testosterone is the key agent in the medical treatment of female to male GID patients. We conducted a dose-response analysis of testosterone replacement therapy (TRT) in 138 patients to determine the onset of the therapeutic effects. The TRT consisted of intramuscular injection of testosterone enanthate and patients were divided into three groups; 250 mg every two weeks, 250 mg every three weeks and 125 mg every two weeks. The onset of deepening of voice, increase in facial hair and cessation of menses was evaluated in each group. At one month after the start of TRT, the onset of these physical changes was more prevalent in the group receiving the higher dose of testosterone, and there were dose-dependent effects observed between the three treatment groups. On the other hand, at six months after the start of TRT, most of the patients had achieved treatment responses and there were no dose-dependent effects with regard to the percentage of patients with therapeutic effects. No significant side effects were observed in any of the treatment groups. We demonstrated that the early onset of the treatment effects of TRT is dose-dependent, but within six months of starting TRT, all three doses were highly effective. Current study provides useful information to determine the initial dose of TRT and to suggest possible changes that should be made in the continuous dosage for long term TRT.

著者

Yoshihiro Miyake Keiko Tanaka Tetsuo Nishikawa Mitsuhide Naruse Ryoichi Takayanagi Hironobu Sasano Yoshiyu Takeda Hirotaka Shibata Masakatsu Sone Fumitoshi Satoh Masanobu Yamada Hajime Ueshiba Takuyuki Katabami Yasumasa Iwasaki Hirotoshi Tanaka Yusuke Tanahashi Shigeru Suzuki Tomonobu Hasegawa Noriyuki Katsumata Toshihiro Tajima Toshihiko Yanase

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0353, (Released:2013-09-28)

被引用文献数

7 36

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The Research Committee of Disorders of Adrenal Hormones, Japan, undertook a nationwide epidemiological study of primary aldosteronism (PA). The present study was undertaken as a part of this study to reveal the relationship between type of treatment and the prognosis of PA. In the primary survey, 4161 patients with PA during the period January 1, 2003-December 31, 2007 were reported from 3252 departments of internal medicine, pediatrics and urology. In the secondary survey, a questionnaire that requested detailed clinical information on individual patients was sent to those departments reporting patients in the primary survey. In total, data on 1706 patients with PA were available in the present study. Among patients with bilateral or unilateral aldosterone-producing adenoma, after adjustment for age at which prognosis was examined, sex, surgical treatment and medical treatment, surgical treatment was significantly associated with amelioration of hypertension (adjusted odds ratio [OR]: 0.47 [95% confidence interval (CI): 0.29–0.77]) and hypokalemia (adjusted OR: 0.17 [95% CI: 0.11–0.29]). No significant relationship was observed between medical treatment and such prognosis in this group of patients. Among patients with bilateral or unilateral adrenal hyperplasia, surgical, but not medical, treatment was significantly associated with amelioration of hypokalemia (adjusted OR: 0.23 [95% CI: 0.06–0.74]), while there was no relationship between surgical or medical treatment and the prognosis of hypertension. In conclusion, surgery offered a better prognosis of PA than medication with regards to hypertension and hypokalemia, with the limitation that a new anti-aldosterone drug, eplerenone, was not available during the study period.

著者

Ayhan ZENGI Muammer KARADENIZ Mehmet ERDOGAN Ahmet Gökhan OZGEN Fusun SAYGILI Candeger YILMAZ Taylan KABALAK

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.55, no.2, pp.325-330, 2008 (Released:2008-05-10)

参考文献数

25

被引用文献数

5 8

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Besides the genetic and environmental factors, radiation is an important aetiological cause in the occurrence of thyroid cancer (TC), particularly papillary carcinoma. Chernobyl disaster led to a dramatic increase in the frequency of TC in Eastern Europe. We aimed to determine the data of TC in our unit from 1982 to 2006 and whether Chernobyl disaster has a possible effect on TC distribution. The data of 351 patients with TC are reviewed retrospectively. The dates at diagnosis were classified in five time periods. The ratios of TCs in our unit were concordant with the literature. Comparing the five 5-year periods, there was a significant decrease in the ratio of follicular carcinoma (p<0.01) although the ratio of other thyroid cancers did not change (p>0.05). The ratio of papillary microcarcinoma increased (p<0.01) while the ratio of classical form decreased (p<0.01). The differences between the time periods and the mean ages at diagnosis for each TCs were not significant (p>0.05). If Chernobyl disaster had any effect, the mean age at diagnosis would be younger. The decrease in the ratio of follicular carcinoma in our study may be due to iodine supplementation. The higher ratio of papillary microcarcinoma can be related to increased diagnostic scrutiny. Epidemiological studies are necessary to determine TC incidence in Turkey.

著者

Hiroaki Kurahashi Masami Watanabe Morito Sugimoto Yuichi Ariyoshi Sabina Mahmood Motoo Araki Kazushi Ishii Yasutomo Nasu Atsushi Nagai Hiromi Kumon

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

pp.EJ13-0203, (Released:2013-09-18)

被引用文献数

1 42

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Gender identity disorder (GID) results from a disagreement between a person’s biological sex and the gender to which he or she identifies. With respect to the treatment of female to male GID, testosterone replacement therapy (TRT) is available. The uric acid (UA) level can be influenced by testosterone; however, the early effects and dose-dependency of TRT on the serum UA concentration have not been evaluated in this population. We herein conducted a dose-response analysis of TRT in 160 patients with female to male GID. The TRT consisted of three treatment groups who received intramuscular injections of testosterone enanthate: 125 mg every two weeks, 250 mg every three weeks and 250 mg every two weeks. Consequently, serum UA elevation was observed after three months of TRT and there was a tendency toward testosterone dose-dependency. The onset of hyperuricemia was more prevalent in the group who received the higher dose. We also demonstrated a positive correlation between increased levels of serum UA and serum creatinine. Since the level of serum creatinine represents an individual’s muscle volume and the muscle is a major source of purine, which induces UA upregulation, the serum UA elevation observed during TRT is at least partially attributed to an increase in muscle mass. This is the first study showing an association between serum UA elevation and a TRT-induced increase in muscle mass. The current study provides important information regarding TRT for the follow-up and management of the serum UA levels in GID patients.

著者

Seiji FUKUMOTO

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.55, no.1, pp.23-31, 2008 (Released:2008-03-13)

参考文献数

52

被引用文献数

39 103

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Fibroblast growth factors (FGFs) are humoral factors with diverse biological functions. While most FGFs were shown to work as local factors regulating cell growth and differentiation, recent investigations indicated that FGF19 subfamily members, FGF15/19, FGF21 and FGF23 work as systemic factors. FGF15/19 produced by intestine inhibits bile acid synthesis and FGF21from liver is involved in carbohydrate and lipid metabolism. In addition, FGF23 was shown to be produced by bone and regulate phosphate and vitamin D metabolism. Furthermore, these FGFs require klotho or βklotho for their actions in addition to canonical FGF receptors. It is possible that these FGFs together with their receptor systems might be targets for novel therapeutic measures in the future.

著者

Yasuhiro ITO Mitsuhiro FUKUSHIMA Chisato TOMODA Hiroyuki INOUE Minoru KIHARA Takuya HIGASHIYAMA Takashi URUNO Yuuki TAKAMURA Akihiro MIYA Kaoru KOBAYASHI Fumio MATSUZUKA Akira MIYAUCHI

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.56, no.6, pp.759-766, 2009 (Released:2009-09-25)

参考文献数

15

被引用文献数

55 108

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Lymph node metastasis is an important clinicopathological feature of papillary thyroid carcinoma (PTC). PTC having clinically apparent lateral node metastasis detectable on preoperative imaging studies (N1b) is known to show a dire prognosis. However, N1b cases include various levels of biological aggressiveness, depending on the size, number, laterality and invasiveness of metastatic nodes. We investigated differences in the prognoses of 621 N1b patients based on these features and compared their prognoses with those of 4297 patients without clinically apparent metastasis (N0) and 125 patients with clinically apparent central node metastasis only (N1a). Disease-free survival (DFS) and cause-specific survival (CSS) of N1b or N1a patients were significantly worse than those of N0 patients, but the prognosis of N1b patients did not differ from that of N1a patients. In the subset of N1b patients, metastatic nodes larger than 3cm, extranodal extension, or 5 or more clinically apparent metastatic nodes independently affected DFS and a combination of the former two features also showed an effect on CSS on multivariate analysis. Prognosis of N1b patients who had none of these features did not differ from that of N1a patients. It is therefore suggested that N1b patients having metastasis larger than 3cm, those showing extranodal extension, and those having 5 or more clinically apparent metastasis should regarded as high-risk, and that careful surgical treatment and postoperative follow-up are necessary.

著者

Yasuhiro Ito Takumi Kudo Minoru Kihara Yuuki Takamura Kaoru Kobayashi Akihiro Miya Akira Miyauchi

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.2, pp.119-125, 2012 (Released:2012-02-29)

参考文献数

13

被引用文献数

10 44

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It is well-known that papillary thyroid carcinoma (PTC) has a generally indolent character and shows a favorable prognosis unless it has no high-risk features such as clinical lymph node metastasis, distant metastasis, and significant extrathyroid extension. In this study, we investigated the prognosis of 3,965 patients with PTC without these features. We classified these patients into 3 groups: T-1, tumor ≤ 2 cm (n = 2,591); T-2, tumor 2.1-4 cm (n = 1,123); T-3, tumor > 4 cm (n = 251). Ten-year recurrence rates of T-1, T-2, and T-3 patients were 0.3, 1.3, and 1.9% for the thyroid (in the subset of patients who underwent limited thyroidectomy), 1.9, 4.6, and 8.1% for lymph nodes, and 0.4, 1.6, and 3.4% for distant organs, respectively. A tumor size larger than 2 cm had an independent prognostic impact on all these recurrences also on multivariate analysis. These findings suggest that PTC larger than 2 cm exhibited more aggressive biological characteristics than that measuring 2 cm or less, even though it had no other high-risk features. However, the incidences of distant recurrence and carcinoma death were still low and it remains unclear whether extensive surgery is mandatory for otherwise low-risk PTC patients with large tumor.

著者

Eiji Kawasaki

出版者

(社)日本内分泌学会

雑誌

Endocrine Journal (ISSN:09188959)

巻号頁・発行日

vol.59, no.7, pp.531-537, 2012 (Released:2012-07-31)

参考文献数

31

被引用文献数

13 44

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Zinc is essential for the proper storage, secretion, and the action of insulin and is transported from cytoplasm to insulin secretory granules in the pancreatic β-cells by SLC30A zinc transporters (ZnT). ZnT8 is specifically expressed in the pancreatic β-cells and has been identified as a novel target autoantigen in patients with type 1 diabetes. Autoantibodies to ZnT8 (ZnT8A) are detected in 50-60% of Japanese patients with acute-onset and 20% with slow-onset type 1 diabetes. Furthermore, humoral autoreactivity to ZnT8 is unique in terms of a key determinant, which is not reported on other islet autoantigens such as insulin, glutamic acid decarboxylase, or the protein tyrosine phosphatase-related molecules IA-2. Type 2 diabetes-associated nonsynonymous single nucleotide polymorphism in SLC30A8 (the gene of ZnT8), rs13266634 (Arg325Trp), modulates ZnT8A specificities thereby indicating that this amino acid substitution has the critical role in antibody binding. The humoral autoreactivity to ZnT8 depends on the clinical phenotype, which may provide clues to understand the role of this protein in the pathogenesis of type 1 diabetes.