Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 62 , Issue 5
Showing 1-10 articles out of 10 articles from the selected issue
REVIEW
  • Satoshi Narumi, Tomonobu Hasegawa
    2015 Volume 62 Issue 5 Pages 393-398
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 21, 2015
    JOURNALS FREE ACCESS
    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.
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ORIGINALS
  • Kumiko Tanaka, Yoshifumi Saisho, Toshihide Kawai, Masami Tanaka, Shu M ...
    2015 Volume 62 Issue 5 Pages 399-409
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: February 26, 2015
    JOURNALS FREE ACCESS
    There is little information on direct comparison between metformin and glucagon-like peptide-1 (GLP-1) receptor agonists in the Asian population. This study examined the efficacy and safety of liraglutide monotherapy compared with metformin monotherapy in overweight/obese Japanese patients with type 2 diabetes (T2DM). The study was a 24-week, open-labeled, randomized controlled study. Overweight or obese patients with T2DM aged 20-75 years with suboptimal glycemic control were randomized to liraglutide or metformin monotherapy. The primary endpoint was change in HbA1c at week 24. Secondary endpoints included changes in daily glycemic profile, body weight, incidence of hypoglycemia and other adverse events. The study, which was originally planned to enroll 50 subjects in each group, was ended with insufficient recruitment. A total of 46 subjects completed the study, and analysis was conducted in this cohort. Reduction in HbA1c at week 24 was comparable between the metformin (n = 24) and liraglutide (n = 22) groups (-0.95 ± 0.80% vs. -0.80 ± 0.88%, p = 0.77), while the liraglutide group reached maximal reduction more rapidly than did the metformin group. There was no significant difference in weight gain or incidence of hypoglycemia between the groups. Diarrhea was more frequent in the metformin group, while constipation was more frequent in the liraglutide group. There was no significant difference in treatment satisfaction between the groups. In conclusion, liraglutide and metformin monotherapy showed similar reduction in HbA1c during 24 weeks, with no difference in weight gain or incidence of hypoglycemia in overweight or obese Japanese patients with T2DM.
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  • Nagaaki Tanaka, Yoshikazu Hiura
    2015 Volume 62 Issue 5 Pages 411-416
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: February 21, 2015
    JOURNALS FREE ACCESS
    The analogue insulin glulisine (Glu) shows both more rapid onset and shorter duration of action compared with the other rapid-acting insulin analogues. The current study investigates these properties in regard to the occurrence of hypoglycemia related to exercise. A randomized, single-center, open-label, crossover study was conducted in 12 hospitalized type 2 diabetes patients (all male, mean ± SD age of 51.9 ± 11.3 years; BMI: 25.5 ± 3.9 kg/m2; HbA1c: 11.2 ± 2.4 %). Glu or insulin aspart (Asp) was subcutaneously administered just before breakfast. Insulin dosage was determined as the usual dose of pre-prandial rapid-acting insulin for patients treated with insulin therapy or as 0.1 unit/kg for patients treated with oral anti-hyperglycemic agents. Sixty min after the start of eating, the patients began aerobic exercise on a bicycle ergometer for 30 min at 50% of maximum heart rate. Hypoglycemic episodes (plasma glucose level < 70 mg/dL with or without symptoms) were observed more frequently in Asp group (p < 0.05). Post-exercise plasma glucose levels at 90, 120, and 150 min were significantly lower in Asp group (p < 0.05). In patients with BMI < 25 kg/m2 (n = 6), post-exercise blood glucose levels were significantly lower in Asp group (p < 0.05), while in patients with BMI ≥ 25 kg/m2 (n = 6) the difference was not significant. Glu may therefore be a suitable choice of rapid-acting insulin for patients with type 2 diabetes who are at high risk of post-exercise hypoglycemia.
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  • Hodaka Yamada, Tomoyuki Saito, Atsushi Aoki, Tomoko Asano, Masashi Yos ...
    2015 Volume 62 Issue 5 Pages 417-421
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 05, 2015
    JOURNALS FREE ACCESS
    There is evidence that betatrophin, a hormone derived from adipose tissue and liver, affects the proliferation of pancreatic beta cells in mice. The aim of this study was to examine circulating betatrophin concentrations in Japanese healthy controls and patients with type 1 and type 2 diabetes. A total of 76 subjects (12 healthy controls, 34 type 1 diabetes, 30 type 2 diabetes) were enrolled in the study. Circulating betatrophin was measured with an ELISA kit and clinical parameters related to betatrophin were analyzed statistically. Circulating betatrophin (Log transformed) was significantly increased in patients with diabetes compared with healthy subjects (healthy controls, 2.29 ± 0.51; type 1 diabetes, 2.94 ± 0.44; type 2 diabetes, 3.17 ± 0.18; p<0.001, 4.1 to 5.4 times in pg/mL order). Age, HbA1c, fasting plasma glucose and Log triglyceride were strongly associated with Log betatrophin in all subjects (n=76) in correlation analysis. In type 1 diabetes, there was a correlation between Log betatrophin and Log CPR. These results provide the first evidence that circulating betatrophin is significantly elevated in Japanese patients with diabetes. The findings of this pilot study also suggest a possibility of association between the level of betatrophin and the levels of glucose and triglycerides.
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  • Hiroshi Kumagai, Asako Zempo-Miyaki, Toru Yoshikawa, Takehiko Tsujimot ...
    2015 Volume 62 Issue 5 Pages 423-430
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 01, 2015
    JOURNALS FREE ACCESS
    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.
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  • Mieno Shiraishi, Yoritsuna Yamamoto, Nobutaka Hirooka, Yasuhiro Obuchi ...
    2015 Volume 62 Issue 5 Pages 431-440
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 16, 2015
    JOURNALS FREE ACCESS
    Although thyroid hormone is a known stimulator of erythropoietic differentiation, severe anemia is sometimes observed in patients with hyperthyroidism and this mechanism is not fully understood. The aim of this study was to investigate the effect of triiodothyronine (T3) on hemin-induced erythropoiesis. Human erythroleukemia K562 cells were used as an erythroid differentiation model. Cell differentiation was induced by hemin and the effect of pre-incubation with T3 (0.1 to 100 nM) was analyzed by measuring the benzidine-positive rate, hemoglobin content, CD71 expression (transferrin receptor), and mRNA expression for transcription factors related to erythropoiesis and thyroid hormone receptors (TRs). Hemin, a promoter of erythroid differentiation, increased the levels of mRNAs for TRα, TRβ, and retinoid X receptor α (RXRα), as well as those for nuclear factor-erythroid 2 (NFE2), GATA-binding protein 1 (GATA1) and GATA-binding protein 2 (GATA2). Lower concentrations of T3 had a stimulatory effect on hemin-induced hemoglobin production (1 and 10 nM), CD71 expression (0.1 nM), and α-globin mRNA expression (1 nM), while a higher concentration of T3 (100 nM) abrogated the stimulatory effect on these parameters. T3 at 100 nM did not affect cell viability and proliferation, suggesting that the abrogation of erythropoiesis enhancement was not due to toxicity. T3 at 100 nM also significantly inhibited expression of GATA2 and RXRα mRNA, compared to 1 nM T3. We conclude that a high concentration of T3 attenuates the classical stimulatory effect on erythropoiesis exerted by a low concentration of T3 in hemin-induced K562 cells.
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  • Yoshihiro Sekiguchi, Yuki Miyamoto, Ichiro Kasahara, Yoshihito Hara, Y ...
    2015 Volume 62 Issue 5 Pages 441-447
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 29, 2015
    JOURNALS FREE ACCESS
    A 32-year-old Chinese woman with rapid weight gain and progressive edema was found to have typical Cushingoid features. Her endocrine data were consistent with a diagnosis of ACTH-dependent Cushing’s syndrome. To differentiate ectopic ACTH syndrome (EAS) from Cushing’s disease (CD), various dynamic endocrine and imaging tests were performed. Her ACTH response was negative to corticotropin-releasing hormone (CRH) and positive to desmopressin. Magnetic resonance imaging of the pituitary showed no mass lesion. Computed tomography scan of the chest revealed a large mass (21 × 15 mm) in the anterior mediastinum, where positron emission tomography showed accumulation of [18F] fluorodeoxyglucose. Selective venous sampling showed marked step-up in ACTH level in the internal thoracic vein but not in the cavernous sinus after CRH stimulation. These data are compatible with the diagnosis of EAS. The resected tumor was pathologically consistent with thymic neuroendocrine tumor (NET) positive for ACTH by immunohistochemistry and abundant V1b receptor gene expression by RT-PCR. Postoperatively, her circulating ACTH/cortisol levels became normalized, and responded to stimulation with CRH but not with desmopressin. Her Cushingoid appearance gradually disappeared, and she was free from recurrence 5 years after surgery. This is a rare case of desmopressin-responsive EAS caused by thymic NET with predominant V1b gene expression, which was successfully localized by imaging modalities combined with selective venous sampling.
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  • Hae Kyung Yang, Kyung Wan Min, Sung Woo Park, Choon Hee Chung, Kyong S ...
    2015 Volume 62 Issue 5 Pages 449-462
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: March 27, 2015
    JOURNALS FREE ACCESS
    The aim of this study was to evaluate the efficacy and safety of anagliptin in drug-naïve patients with type 2 diabetes in a double-blind randomized placebo-controlled study. A total of 109 patients were randomized to 100 mg (n=37) or 200 mg (n=33) anagliptin twice daily or placebo (n=39). The primary objective was to alter HbA1c levels from baseline at a 24-week endpoint. The overall baseline mean age and body mass index were 56.20 ± 9.77 years and 25.01 ± 2.97 kg/m2, respectively, and the HbA1c level was of 7.14 ± 0.69 %. Anagliptin at 100 mg and 200 mg produced significant reductions in HbA1c (-0.50 ± 0.45 % and -0.51 ± 0.55%, respectively), and the placebo treatment resulted in an increase in HbA1c by 0.23 ± 0.62 %. Both doses of anagliptin produced significant decreases in fasting plasma glucose (-0.53 ± 1.25 mmol/L and -0.72 ± 1.25 mmol/L, respectively) and the proinsulin/insulin ratio (-0.04 ± 0.15 and -0.07 ± 0.18, respectively) compared with placebo. No meaningful body weight changes from baseline were observed in three groups. Plasma dipeptidyl peptidase (DPP)-4 activity was significantly inhibited after 24 weeks of anagliptin treatment, and >75% and >90% inhibitions were observed during the meal tolerance tests with 100 mg and 200 mg anagliptin, respectively. The incidences of adverse or serious adverse events were similar among the three study groups. Twice-daily anagliptin therapy effectively inhibited DPP-4 activity and improved glycemic control and was well-tolerated in patients with type 2 diabetes.
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NOTE
  • Birgit Harbeck, Swantje Brede, Claudia Witt, Sven Süfke, Hendrik ...
    2015 Volume 62 Issue 5 Pages 463-468
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: February 26, 2015
    JOURNALS FREE ACCESS
    Adrenal insufficiency (AI) is a rare disease caused by destruction of the adrenal glands or dysfunction of the pituitary gland or the hypothalamus. Treatment usually requires lifelong replacement therapy with glucocorticoids. Correct use of glucocorticoids and early dose adjustments are essential to cover the increased glucocorticoid demand in stress. Repeated education of patients and their partners is the best strategy to avoid life-threatening emergencies. However, there is a debate whether physicians’ knowledge regarding AI is sufficient, in part due to the rareness of this endocrine disorder. To determine the present specific knowledge of physicians in a large University Department of Internal Medicine with a clinically and scientifically active Division of Endocrinology, all interns, residents / fellows, specialists or senior physicians / consultants were asked to complete a questionnaire with various possible answers on the subject of AI (n=69, median age 30 years, range 23-49 years). The present data suggest that in the investigated University Hospital setting current physicians’ knowledge of medical replacement strategies in AI may be insufficient depending on the level of education and experience. Even physicians with training in endocrinology in part demonstrated extensive knowledge gaps. There might be a need for additional structured information and training on AI, even in specialized hospitals.
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RAPID COMMUNICATION
  • Tsutomu Sasaki, Haruna Hiraga, Hiromi Yokota-Hashimoto, Tadahiro Kitam ...
    2015 Volume 62 Issue 5 Pages 469-473
    Published: 2015
    Released: May 31, 2015
    [Advance publication] Released: April 02, 2015
    JOURNALS FREE ACCESS
    Miglitol is an absorbable alpha-glucosidase inhibitor that is used to control post-prandial hyperglycemia. We previously found that miglitol stimulates brown adipose tissue and prevents diet-induced obesity in mice that are fed a high-fat, high-carbohydrate diet. In this study, we examined whether miglitol can also protect against aging-dependent weight gain in mice that are fed a normal chow diet. Male C57Bl/6J mice were fed normal chow with or without miglitol (800 ppm) for 12 weeks, starting at 12 weeks of age. Food intake and body weight were monitored. After 12 weeks, adiposity, energy expenditure, and locomotor activities were measured. After sacrifice, weight of the epididymal white adipose tissue and adipocyte size were measured. Finally, Ucp1 gene expression and UCP1 protein abundance in brown adipose tissue were quantified by RT-PCR and Western analyses, respectively. Miglitol prevented age-related weight gain without affecting growth of the animals. Miglitol-treated mice showed reduced adiposity and increased oxygen consumption compared to controls, accompanied by higher UCP1 protein abundance in brown adipose tissue. Food intake and locomotor activities were not affected. These results suggest that miglitol can protect against age-dependent weight gain. Elucidating the molecular targets of miglitol in brown adipose tissue and optimizing drug delivery and efficacy may provide new strategies to combat obesity.
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