著者
Akira Shimatsu Noriyuki Iwamoto Toshiaki Tanaka Akira Teramoto Masanori Taketsuna Katsuichiro Ihara Jumpei Funai Minoru Irie Kazuo Chihara
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.62, no.8, pp.749-756, 2015 (Released:2015-08-29)
参考文献数
27

In addition to impaired physical activity, adult GH deficiency (GHD) can decrease quality of life (QOL). Hence, assessment of QOL is important to evaluate the efficacy of GH replacement therapy. This study aimed to identify factors that may be predictive of long-term improvement in QOL among clinical/laboratory variables during GH replacement therapy. The analysis included 83 Japanese adults with GHD who participated in the Hypopituitary Control and Complications Study (HypoCCS). Correlations between the change from baseline in clinical/laboratory variables at 6 months and the change from baseline in Quality of life (Short-Form 36 [SF-36] component scores) at 12 months were examined. Unexpectedly, all component scores were negatively correlated with the change in fasting plasma glucose concentration (FPG) (physical component summary [PCS], r = -0.456; mental component summary [MCS], r = -0.523; role/social component summary [RCS], r = -0.433). The change in MCS was positively correlated with the change in insulin-like growth factor-1 standard deviation score (IGF-1 SDS) (r = 0.417). The change in PCS was positively correlated with the change in body fat (r = 0.551). The change in RCS was positively correlated with the change in waist circumference (r = 0.528). Short-term changes in several clinical/laboratory variables, most notably FPG and IGF-1 SDS, were correlated with long-term changes in QOL. The clinical importance of these correlations for predicting GH replacement treatment efficacy warrants further investigation.
著者
Akinori Hayashi Koji Takano Sayuki Kawai Masayoshi Shichiri
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.63, no.2, pp.187-191, 2016 (Released:2016-02-29)
参考文献数
9
被引用文献数
2 10

Diabetes mellitus complicated with insulin antibodies is rare in clinical practice but usually difficult to control. A high amount of insulin antibodies, especially with low affinity and high binding capacity, leads to unstable glycemic control characterized by hyperglycemia unresponsive to large volume of insulin and unanticipated hypoglycemia. There are several treatment options, such as changing insulin preparation, immunosupression with glucocorticoids, and plasmapheresis, most of which are of limited efficacy. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of drug which decrease renal glucose reabsorption and lowers plasma glucose level independent of insulin action. We report here a case with diabetes complicated with insulin antibodies who was effectively controlled by an SGLT2 inhibitor. A 47-year-old man with type 2 diabetes treated with insulin had very poor glycemic control characterized by postprandial hyperglycemia unresponsive to insulin therapy and repetitive hypoglycemia due to insulin antibodies. Treatment with ipragliflozin, an SGLT2 inhibitor, improved HbA1c from 8.4% to 6.0% and glycated albumin from 29.4% to 17.9%. Continuous glucose monitoring revealed improvement of glycemic profile (average glucose level from 212 mg/dL to 99 mg/dL and glycemic standard deviation from 92 mg/dL to 14 mg/dL) with disappearance of hypoglycemic events. This treatment further ameliorated the characteristics of insulin antibodies and resulted in reduced insulin requirement. SGLT2 inhibitors may offer an effective treatment option for managing the poor glycemic control in diabetes complicated with insulin antibodies.
著者
Yumiko Komatsu Akinobu Nakamura Masahiro Takihata Yuichiro Inoue Satoko Yahagi Kazuki Tajima Hirohisa Tsuchiya Tatsuro Takano Tadashi Yamakawa Masahiro Yoshida Hideaki Miyoshi Yasuo Terauchi
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.63, no.3, pp.311-314, 2016 (Released:2016-03-31)
参考文献数
11
被引用文献数
2 13

Diazoxide is a non-diuretic benzothiadiazine derivative, one of a group of substances introduced into clinical practice in the 1950s for the treatment of hypertension. Fajans reported the use of diazoxide for the treatment of insulinoma in 1979. Although patients with hyperinsulinemic hypoglycemia worldwide have been treated with diazoxide for more than 30 years, there are no recent reports about the adverse effects of this drug in Asian patients, including Japanese patients. Herein, we report the results of our retrospective clinical record review of 6 Japanese patients (3 females and 3 males, ranging in age from 58 to 91 years) with hyperinsulinemic hypoglycemia and inoperable insulinoma treated with diazoxide. Diazoxide improved control of hypoglycemic symptoms and maintained normoglycemia in 5 of the 6 patients, and was ineffective in one patient. Surprisingly, although all 6 patients received diazoxide according to the treatment strategy recommended in Western patients, 5 of the 6 patients developed edema and two developed congestive heart failure. Thus, when starting treatment with diazoxide in Japanese patients, the symptoms and signs of fluid retention should be evaluated carefully. Also, appropriate protocols for treatment with diazoxide should be evaluated by means of clinical trials in Japanese patients with hyperinsulinemic hypoglycemia.
著者
Junichiro Sato Noriko Makita Taroh Iiri
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ16-0084, (Released:2016-03-08)
被引用文献数
25

In the classical two-state model, G protein-coupled receptors (GPCRs) are considered to exist in equilibrium between an active and an inactive conformation. Thus, even at the resting state, some subpopulation of GPCRs is in the active state, which underlies the basal activity of the GPCRs. In this review, we discuss inverse agonists, which are defined as GPCR ligands that shift the equilibrium toward the inactive state and thereby suppress the basal activity. Theoretically, if constitutive activation plays an essential role in the pathogenesis of a disease, only inverse agonists, and not neutral antagonists, can reverse this pathophysiological activation. Although many pharmacological examples of inverse agonism have been identified, its clinical importance is still unclear and debated. Thus, even though inverse agonism of angiotensin receptor blockers (ARBs) has been discussed for more than 10 years, its clinical relevance remains to be completely clarified.
著者
Xi Xie Wenyuan Li Tian Lan Weihua Liu Jing Peng Kaipeng Huang Juan Huang Xiaoyan Shen Peiqing Liu Heqing Huang
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.58, no.9, pp.761-768, 2011 (Released:2011-09-30)
参考文献数
35
被引用文献数
14 40

Recently, it is implicated that the abnormality of Akt signaling pathway is involved in the diabetic pathology. Previous studies have demonstrated that berberine could decrease blood glucose by elevating liver glycogen synthesis. However, the underlying mechanism is still unclear. In the present study, we investigated the effects of berberine on fasting blood glucose, liver glycogen, Akt, Glycogen synthase kinase-3, glucokinase and insulin receptor substrate (IRS) in alloxan-induced diabetic mice, exploring its possible hypoglycemic mechanism. We found that in alloxan-induced diabetic mice, the high blood glucose was significantly lowered by berberine treatment. Liver glycogen content, the expression and activity of glucokinase and the phosphorylated Akt and IRS were all significantly reduced in diabetic mice whereas berberine blocked these changes. Berberine also depressed the increasing of phosphorylated GSK-3β in diabetic mice. Collectively, Berberine upregulates the activity of Akt possibly via insulin signaling pathway, eventually lowering high blood glucose in alloxan-induced diabetic mice.
著者
Yo Kunii Takashi Uruno Koji Mukasa Kenichi Sekiya Kenji Iwaku Akifumi Suzuki Kiminori Sugino Jaeduk Yoshimura Noh Koichi Ito
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.63, no.1, pp.21-27, 2016 (Released:2016-01-31)
参考文献数
20
被引用文献数
1 5

In the event of a nuclear power plant accident, prophylactic administration of potassium iodide (KI) is recommended to prevent thyroid damage due to uptake of radioiodine. To assess the inhibitory effect of low-dose inorganic iodine on thyroidal radioactive iodine uptake (RAIU) in healthy adults without dietary iodine restriction, single or repeated doses of 10 mg inorganic iodine solution were given to 22 Japanese volunteers, 18 men and 4 women with the mean age of 35.7 years, between 2011 and 2013. Changes in urinary iodine excretion, thyroid function and 24-hour RAIU were also evaluated. The median 24-hour RAIU without iodine restriction was 13 % (range, 5-26 %). A single-dose of 10 mg inorganic iodine suppressed the median 24-hour RAIU measured one hour after iodine administration to 3 % (range, 1-7 %) and, in 90.9% of 22 participants their 24-hour RAIU was < 5 %. For seven participants given 10 mg of inorganic iodine daily for 14 days, the median 24-hour RAIU measured at 24 hours after the last administration of iodine was 6 % (range, 2-12 %), although the inhibitory effect was diminished in two participants. Serum thyroid stimulating hormone concentration was slightly elevated in three participants without decreased serum FT3 and FT4 levels. We conclude that a single-dose of 10 mg inorganic iodine is sufficient to inhibit RAIU in adults, although the inhibitory effect of repeated-dose on RAIU is diminished when KI is given once daily. The dose, duration or interval of iodine administration should be evaluated in iodine-sufficient regions in a future.
著者
Hiroshi Kumagai Asako Zempo-Miyaki Toru Yoshikawa Takehiko Tsujimoto Kiyoji Tanaka Seiji Maeda
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ14-0555, (Released:2015-03-01)
被引用文献数
3 44

Obesity has reached global epidemic proportions and is associated with multiple comorbidities, including cardiovascular disease. A novel predictor of cardiovascular disease is elevated central systolic blood pressure. In fact, lifestyle modifications have been shown to decrease the central systolic blood pressure in overweight and obese men. The mechanism underlying these changes has yet to be fully elucidated. Interestingly, testosterone has been found to have cardioprotective effects. Moreover, serum testosterone levels are lower in obese men than in normal weight men. However, it is still unclear whether testosterone participates in the decrease of central blood pressure in overweight and obese men following lifestyle modifications. So, the purpose of the present study was to investigate the effect of testosterone on central systolic blood pressure in overweight and obese men before and after the 12-week lifestyle modification program. Forty-four overweight and obese men completed a 12-week lifestyle modification program (aerobic exercise training and dietary modifications). For all participants, central systolic blood pressure and serum testosterone levels were measured before and after the program. After the program, central systolic blood pressure was significantly decreased while serum total testosterone levels were significantly increased in overweight and obese men. Moreover, we also found a significant negative relationship between the change in serum testosterone levels and that in central systolic blood pressure. The present study suggests that increased serum testosterone levels likely contribute to a decrease in central blood pressure in overweight and obese men.
著者
Radan Dzodic Marko Buta Ivan Markovic Dusica Gavrilovic Milovan Matovic Igor Djurisic Zorka Milovanovic Gordana Pupic Slobodan Tasic Nikola Besic
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.1079-1086, 2014 (Released:2014-11-28)
参考文献数
42
被引用文献数
2 12

Well-differentiated thyroid carcinoma in children and adolescents is rare but demonstrates aggressive behavior. Gross lymph node metastases and distant metastases are common upon first clinical presentation. During a 33-year period (1981-2014) at the Institute of Oncology and Radiology of Serbia, 62 children and adolescents underwent surgery due to well-differentiated thyroid carcinoma. Mean age was 16.7 (range 7-21) years. At the time of diagnosis 6% of patients had lung metastases. Total thyroidectomy or completion thyroidectomy was performed for all patients followed by central neck dissection and frozen section examination of jugular-carotid compartments. Median follow-up was 10.9 (range 0.69-33.05) years and median tumor size was 20 (range 2-60) mm. Papillary carcinoma was found in 96%, and follicular and Hürthle cell carcinoma in 2% of patients. Multifocal tumors were found in 50% and capsular invasion in 60% of patients. Lymphonodal metastases in either central or lateral neck compartments were found in 73% of patients. Multifocality and capsular invasion were significantly more frequent in patients less than 16 years of age (both p<0.01). Median disease-free interval had not been reached and overall survival rate was 100%. Well-differentiated thyroid carcinoma in children and adolescents is characterized by a high rate of loco-regional aggressiveness, multifocality, capsular invasion, lymph node metastases and distant metastases at the time of diagnosis. Adequate surgical approaches should be performed for both primary and recurrent disease in young patients with well-differentiated thyroid carcinoma in order to achieve loco-regional disease control and longer disease-free survival.
著者
Yi X. Chan Matthew W. Knuiman Joseph Hung Mark L. Divitini David J. Handelsman John P. Beilby Brendan McQuillan Bu B. Yeap
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ15-0196, (Released:2015-06-13)
被引用文献数
1 21

Clarifying the relationship of sex hormones to preclinical atherosclerosis could illuminate pathways by which androgens are associated with cardiovascular events and mortality. Our aim was to determine hormone profiles associated with carotid intima-media thickness (CIMT) and carotid atheroma, in men with and without known coronary artery disease (CAD). We included 492 community-based men aged 20-70 years (Group A) and 426 men with angiographically proven CAD aged <60 years (Group B). Fasting early morning sera were assayed for testosterone (T), dihydrotestosterone (DHT) and estradiol (E2) using mass spectrometry. CIMT and carotid plaque were assessed ultrasonographically. Mean (±SD) age was Group A: 53.8±12.6 and Group B: 49.6±5.1 years. Higher T was associated with reduced CIMT (-0.011 mm per 1-SD increase, p=0.042) and lower prevalence of carotid plaque (odds ratio [OR] per 1-SD increase, 0.68, p=0.012) in Group A, but not B. E2 was associated with increased CIMT in Group A (0.013 mm, p=0.011) but not B. Higher DHT and E2 were associated with reduced carotid plaque in Group B (DHT: OR=0.77, p=0.024; E2: OR=0.75, p=0.008), but not A. In community-dwelling men, higher T is associated with favourable CIMT and lower prevalence of carotid plaque, while higher E2 is associated with worse CIMT. In men with CAD, higher DHT or E2 are associated with less carotid plaque. T, DHT and E2 are differentially associated with preclinical carotid atherosclerosis in a cardiovascular phenotype-specific manner. Interventional studies are needed to examine effects of exogenous T and its metabolites DHT and E2, on atherogenesis.
著者
Alper Sonmez Cem Haymana Aydogan Aydogdu Serkan Tapan Yalcin Basaran Coskun Meric Kamil Baskoy Mustafa Dinc Mahmut Yazici Abdullah Taslipinar Cem Barcin Mahmut Ilker Yilmaz Erol Bolu Omer Azal
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ15-0125, (Released:2015-04-28)
被引用文献数
6

Patients with hypogonadism have poor cardiovascular and metabolic outcomes, and the effect of testosterone replacement therapy (TRT) is not clear. We investigated the presence of inflammation, insulin resistance and endothelial dysfunction in an unconfounded population of congenital hypogonadotrophic hypogonadism (CHH) and the effect of TRT on these subjects. A total of 60 patients with CHH (mean age 21.82±2.22 years) and 70 healthy control subjects (mean age 21.32±1.13 years) were enrolled. The demographic parameters, Asymmetric dimethylarginine (ADMA), TNF-like weak inducer of apoptosis (TWEAK), high sensitive C reactive protein (hs-CRP) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured before and after TRT. The patients had higher Waist Circumferences (WC) (p=0.009), Diastolic Blood Pressures (p=0.02), Triglycerides (p=0.03), ADMA, insulin and HOMA-IR levels (p<0.001 for all) and lower TWEAK levels (p<0.001), compared to the healthy controls. After 5.56±2.04 months of TRT, the patients had significantly elevated systolic blood pressures (p=0.01), body mass indexes and WC (p<0.001 and p=0.001 respectively) and decreased total and HDL cholesterol levels (p=0.032 and p<0.001 respectively). ADMA levels significantly increased (p=0.003), while the alterations in TWEAK, hsCRP and HOMA-IR were not significant. The results of the present study show that endothelial dysfunction, inflammation and insulin resistance are prevalent even in the very young subjects with CHH, who have no metabolic or cardiac problems at present. This increased cardiometabolic risk however, do not improve but even get worse after six months of TRT. Long term follow-up studies are warranted to investigate the unfavorable cardiometabolic effects of TRT.
著者
Tomohiko Urano Satoshi Inoue
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ15-0154, (Released:2015-04-11)
被引用文献数
4 49

Osteoporosis is a skeletal disorder characterized by low bone mineral density (BMD) and an increased susceptibility to fractures. Evidence from genetic studies indicates that BMD, a complex quantitative trait with a normal distribution, is genetically controlled. Genome-wide association studies (GWAS) as well as studies using candidate gene approaches have identified single-nucleotide polymorphisms (SNPs) that are associated with BMD, osteoporosis and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding WNT/β-catenin signaling proteins. Understanding the genetics of osteoporosis will help to identify novel candidates for diagnostic and therapeutic targets. Genetic factors are also important for the development of sarcopenia, which is characterized by a loss of lean body mass, and obesity, which is characterized by high fat mass. Hence, in this review, we discuss the genetic factors, identified by genetic studies, which regulate the body components related to osteoporosis, sarcopenia, and obesity.
著者
Nilgun GUVENER Neslihan Bascil TUTUNCU Sule AKCAY Fusun EYUBOGLU Adnan GOKCEL
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.50, no.6, pp.663-667, 2003 (Released:2003-12-27)
参考文献数
15
被引用文献数
16 31

The present study has been conducted to quantify and compare the capacity of gas exchange in patients with type 2 diabetes mellitus (DM) and healthy controls and also to investigate the effects of various factors on alveolar capillary permeability. A total of 37 subjects, 25 patients with DM and 12 healthy controls were recruited for the study. All the participants were evaluated with simple spirometric tests and simple breath carbonmonoxide (CO) diffusion test (DLCO). The ratio of DLCO value to the alveolar ventilation (VA) was used to assess alveolar membrane permeability. Diabetic patients were also evaluated in detail with respect to degenerative diabetic complications including the presence of microalbuminuria, advanced nephropathy, sensorial and autonomic neuropathy, retinopathy, hypertension and macrovascular disease. The results of simple spirometric tests which determined lung capacity were similar in the diabetic patients and the healthy controls. Ratio of DLCO/VA, which determines alveolar membrane permeability, revealed statistically significant decline in pulmonary gas exchange in the diabetic group (p: 0.037). Pearson correlation analysis revealed statistically significant correlation between duration of diabetes mellitus, age and urinary albumin excretion with DLCO/VA values (Pearson: -0.726, p: 0.001; Pearson: -0.438, p: 0.036; Pearson: -0.472, p: 0.023 respectively). This study demonstrated the decreased alveolar gas exchange capacity in diabetic patients compared with healthy controls. Detrimental effects of DM on alveolar capillaries were found to be correlated with age, duration of DM and urinary albumin excretion. Microalbuminuria was the only significant predictor of DLCO/VA.
著者
Satoshi Narumi Tomonobu Hasegawa
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
pp.EJ15-0131, (Released:2015-03-21)
被引用文献数
1 8

Genetic defects of hormone receptors are the most common form of end-organ hormone resistance. One example of such defects is TSH resistance, which is caused by biallelic inactivating mutations in the TSH receptor gene (TSHR). TSH, a master regulator of thyroid functions, affects virtually all cellular processes involving thyroid hormone production, including thyroidal iodine uptake, thyroglobulin iodination, reuptake of iodinated thyroglobulin and thyroid cell growth. Resistance to TSH results in defective thyroid hormone production from the neonatal period, namely congenital hypothyroidism. Classically, clinical phenotypes of TSH resistance due to inactivating TSHR mutations were thought to vary depending on the residual mutant receptor activity. Nonfunctional mutations in the two alleles produce severe thyroid hypoplasia with overt hypothyroidism (uncompensated TSH resistance), while hypomorphic mutations in at least one allele produce normal-sized thyroid gland with preserved hormone-producing capacity (compensated TSH resistance). More recently, a new subgroup of TSH resistance (nonclassic TSH resistance) that is characterized by paradoxically high thyroidal iodine uptake has been reported. In this article, the pathophysiology and clinical features of TSH resistance due to inactivating TSHR mutations are reviewed, with particular attention to the nonclassic form.
著者
Mie Arakawa Takayuki Masaki Junko Nishimura Masataka Seike Hironobu Yoshimatsu
出版者
(社)日本内分泌学会
雑誌
Endocrine Journal (ISSN:09188959)
巻号頁・発行日
vol.58, no.3, pp.161-170, 2011 (Released:2011-03-31)
参考文献数
42
被引用文献数
19 74

It has been demonstrated the involvement of branched-chain amino acids (BCAA) on obesity and related metabolic disorder. We investigated the effects of branched-chain amino acids (BCAA) on obesity and on glucose/fat homeostasis in mice fed on a high-fat (45%) diet. BCAA was dissolved in 0.5% methylcellulose and added to the drinking water (BCAA-treated group). A high-fat diet was provided for 6 weeks and BCAA was given for 2 weeks. The BCAA-treated group gained almost 7% less body weight and had less epididymal adipose tissue (WAT) mass than the control group (ppp<0.05). These results demonstrate that the liver and muscle TG concentration are less in BCAA-treated group. BCAA affects PPAR-alpha and UCP expression in muscle and liver tissue.
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
62 156

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 13

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

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 28

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 43

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

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.