Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 62 , Issue 1
Showing 1-12 articles out of 12 articles from the selected issue
REVIEW
  • Kennichi Kakudo, Tomoko Wakasa, Yoshio Ohta, Katsunari Yane, Yasuhiro ...
    2015 Volume 62 Issue 1 Pages 1-12
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: September 07, 2014
    JOURNALS FREE ACCESS
    This review emphasizes that the so-called high-risk thyroid carcinoma is not a distinct tumor entity, but a group of tumors with different histologies. High-grade histological features, such as tumor necrosis, increased mitoses, and nuclear pleomorphism, together with high Ki-67 labeling index (more than 10%), are good indicators of high-risk thyroid carcinoma and suggest a possible risk for anaplastic transformation. This review proposes the stratification of patients with thyroid carcinoma into low-, moderate-, and high-risk groups based on Ki-67 labeling index, which should be useful for the clinical management of patients, even after initial surgery. Currently, both the aggressive variant of papillary carcinoma and poorly differentiated carcinoma are aggressively treated by a completion of total thyroidectomy with prophylactic lymph node dissection followed by radioactive iodine treatment. Therefore, patients with moderate-risk or high-risk thyroid carcinoma based on Ki-67 labeling index should also be considered candidates for this treatment strategy.
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ORIGINALS
  • Wakaba Tsuchimochi, Hiroaki Ueno, Eiichiro Yamashita, Chikako Tsubouch ...
    2015 Volume 62 Issue 1 Pages 13-20
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: September 25, 2014
    JOURNALS FREE ACCESS
    Teneligliptin is a novel peptidomimetic-chemotype prolylthiazolidine-based inhibitor of dipeptidyl peptidase-4 (DPP-4). The aim of this study was to evaluate the effects of teneligliptin on 24 h blood glucose control and gastrointestinal hormone responses to a meal tolerance test, and to investigate the glucose-lowering mechanisms of teneligliptin. Ten patients with type 2 diabetes mellitus (T2DM) were treated for 3 days with teneligliptin (20 mg/day). Postprandial profiles for glucose, insulin, glucagon, active glucagon-like peptide-1 (GLP-1), active glucose-dependent insulinotropic polypeptide (GIP), ghrelin, des-acyl ghrelin, and 24 h glycemic fluctuations were measured via continuous glucose monitoring for 4 days. Once daily teneligliptin administration for 3 days significantly lowered postprandial and fasting glucose levels. Significant elevations of fasting and postprandial active GLP-1 and postprandial active GIP levels were observed. Teneligliptin lowered postprandial glucose elevations, 24 h mean blood glucose levels, standard deviation of 24 h glucose levels and mean amplitude of glycemic excursions (MAGE) without hypoglycemia. Serum insulin levels in the fasting state and 30 min after a meal were similar before and after teneligliptin treatment; however significant reductions at 60 to 180 min after treatment were observed. A significant elevation in early-phase insulin secretion estimated by insulinogenic and oral disposition indices, and a significant reduction in postprandial glucagon AUC were observed. Both plasma ghrelin and des-acyl ghrelin levels were unaltered following teneligliptin treatment. Teneligliptin improved 24 h blood glucose levels by increasing active incretin levels and early-phase insulin secretion, reducing the postprandial insulin requirement, and reducing glucagon secretion. Even short-term teneligliptin treatment may offer benefits for patients with T2DM.
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  • Noriaki Fukuhara, Kentaro Horiguchi, Hiroshi Nishioka, Hisanori Suzuki ...
    2015 Volume 62 Issue 1 Pages 21-27
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 01, 2014
    JOURNALS FREE ACCESS
    Preoperative control of hyperthyroidism in patients with TSH-secreting pituitary adenomas (TSHoma) may avoid perioperative thyroid storm. Perioperative administration of octreotide may control hyperthyroidism, as well as shrink tumor size. The effects of preoperative octreotide treatment were assessed in a large number of patients with TSHomas. Of 81 patients who underwent surgery for TSHoma at Toranomon Hospital between January 2001 and May 2013, 44 received preoperative short-term octreotide. After excluding one patient because of side effects, 19 received octreotide as a subcutaneous injection, and 24 as a long-acting release (LAR) injection. Median duration between initiation of octreotide treatment and surgery was 33.5 days. Octreotide normalized free T4 in 36 of 43 patients (84%) and shrank tumors in 23 of 38 (61%). Length of octreotide treatment did not differ significantly in patients with and without hormonal normalization (p = 0.09) and with and without tumor shrinkage (p = 0.84). Serum TSH and free T4 concentrations, duration of treatment, incidence of growth hormone (GH) co-secretion, results of octreotide loading tests, form of administration (subcutaneous injection or LAR), tumor volume, and tumor consistency did not differ significantly in patients with and without hormonal normalization and with and without tumor shrinkage. Short-term preoperative octreotide administration was highly effective for TSHoma shrinkage and normalization of excess hormone concentrations, with tolerable side effects.
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  • Jiewei Luo, Xiao Yang, Jixing Liang, Weihua Li
    2015 Volume 62 Issue 1 Pages 29-36
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 02, 2014
    JOURNALS FREE ACCESS
    Gitelman syndrome (GS) is a salt-wasting tubulointerstitial disease of autosomal recessive inheritance (OMIM613395) caused by genic mutation of SLC12A3, which codes thiazide-sensitive Na-Cl cotransporter (NCCT) gene. The gene mutation of the majority of GS patients is compound heterozygous. This study analyzes two cases of GS gene mutation and the clinical phenotype. Twenty patients of two GS pedigrees underwent direct sequence alignment of 26 exons of SLC12A3 to spot and locate mutant site. Proband A of Pedigree I had three mutant sites: Arg928Cys, a homozygote, missense mutation, and two homozygous silent mutations, Ala122Ala and Thr465Thr, and 8 members of Pedigree I carried Arg928Cy heterozygous mutation. Proband B of Pedigree II had a homozygote, Ser710X, and a termination codon was spotted, which would inevitably be translated into abridged and defective protein, and 7 members had Ser710X heterozygous mutation. The heterozygous mutation carriers of the two pedigrees often have stimulus-controlled hypokalemia after strenuous exercise. The parents of Proband A are cousins, a case of intermarriage. Both probands show hypokalemia, hypochloraemia, hypocalcinuria, hyperreninemia, and hyperaldosteronemia; Proband A has normal serum magnesium and increased urinary sodium excretion, while Proband B has hypomagnesemia and increased urinary magnesium ion excretion. Both probands have normal or lower blood pressure, weakness and numbness of lower extremities, muscular soreness, and occasional palpitations and chest discomfort. Proband A wearies easily and Proband B has occasional joint numbness and pain. These two homozygous mutations are responsible for the morbidity of two GS families and they show heterogenicity of clinical phenotype.
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  • Wataru Nishimura, Hisashi Oishi, Nobuaki Funahashi, Toshiyoshi Fujiwar ...
    2015 Volume 62 Issue 1 Pages 37-51
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 01, 2014
    JOURNALS FREE ACCESS
    MafA and MafB are basic leucine zipper transcription factors expressed in mature pancreatic β- and α-cells, respectively. MafA is not only an insulin gene transcription factor but is also critical for the maturation and maintenance of β-cell function, whereas MafB is expressed in immature β-cells during development and in compromised β-cells in diabetes. In this study, we developed a mouse model to easily trace the promoter activity of MafA in β-cells as a tool for studying β-cell differentiation, maturation, regeneration and function using the expression of the fluorescent protein Kusabira Orange (KOr) driven by the BAC-mafA promoter. The expression of KOr was highly restricted to β-cells in the transgenic pancreas. By crossing MafA-KOr mice with MafBGFP/+ reporter mice, simultaneous monitoring of MafA and MafB expressions in the isolated islets was successfully performed. This system can be a useful tool for examining dynamic changes in the differentiation and function of pancreatic islets by visualizing the expressions of MafA and MafB.
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  • Kentaro Suda, Hidenori Fukuoka, Genzo Iguchi, Yushi Hirota, Hitoshi Ni ...
    2015 Volume 62 Issue 1 Pages 53-59
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 04, 2014
    JOURNALS FREE ACCESS
    The prevalence of acromegaly is estimated to be 8-24/100,000, but several recent studies suggest it is underestimated. In particular, acromegaly is considered more prevalent in patients with type 2 diabetes mellitus (T2DM) than in the normal population. This study aimed to evaluate the prevalence of acromegaly in hospitalized patients with T2DM. A total of 327 hospitalized patients with T2DM were recruited as subjects. If serum insulin-like growth factor 1 (IGF-1) levels were found to be elevated, random GH level was measured or oral glucose tolerance test (OGTT) was performed. Five patients with elevated serum IGF-1 levels and random GH level or inadequate suppression of GH in the OGTT underwent pituitary magnetic resonance imaging. Of those patients, pituitary adenoma was detected in 2 patients. These 2 patients were diagnosed with acromegaly, as they also exhibited mild acromegalic features. Intriguingly, both these patients exhibited severe macroangiopathy and an absence of microangiopathy. The prevalence of acromegaly in the hospitalized patients with T2DM in this study was therefore 0.6%, suggesting a higher prevalence than that predicted. Although a large-scale prospective study is required to clarify the precise prevalence of acromegaly in hospitalized patients with T2DM, the present study shows that it is useful to screen hospitalized patients with T2DM for acromegaly by measuring their serum IGF-1 level.
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  • Kentaro Miyai, Toshikazu Onishi, Kenichi Kashimada, Yukihiro Hasegawa
    2015 Volume 62 Issue 1 Pages 61-68
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 04, 2014
    JOURNALS FREE ACCESS
    Patients with vitamin D-dependent rickets type 1A (VDDR1A) are usually treated with alfacalcidol, an analog of vitamin D. Around puberty, an increased dose of alfacalcidol is recommended for these patients to avoid hypocalcemia and secondary hyperparathyroidism. However, no indicators of secondary hyperparathyroidism except for PTH are presently known. The aim of this study is to evaluate whether urinary calcium to creatinine ratio (U-Ca/Cr) is useful as a biomarker of secondary hyperparathyroidism in VDDR1A patients in order to determine the proper dose of alfacalcidol. Two brothers with VDDR1A were recruited who had null mutations of CYP27B1 which encodes 1-alpha-hydroxylase of vitamin D. We investigated the relationship between U-Ca/Cr and intact-PTH around puberty when the brothers showed hypocalcemia with secondary hyperparathyroidism. The results were compared to those of five patients with vitamin D deficiency (VDD). As a result, high intact-PTH levels were observed when U-Ca/Cr decreased to less than 0.1 (mg/mg) in both VDDR1A brothers. This relationship was also observed in the VDD patients. However, it is necessary to take into account body calcium status, either in depletion or in excess, to accurately evaluate the relationship between U-Ca/Cr and secondary hyperparathyroidism. First, low U-Ca/Cr was detected in situations with calcium depletion without hyperparathyroidism in the VDDR1A patients. Second, high U-Ca/Cr with hyperparathyroidism could be detected theoretically in a condition of excess calcium supply. In conclusion, a U-Ca/Cr ratio of less than 0.1 (mg/mg) in VDDR1A patients is useful to accurately evaluate calcium depletion and secondary hyperparathyroidism.
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  • Akira Kurozumi, Yosuke Okada, Tadashi Arao, Manabu Narisawa, Keiichi T ...
    2015 Volume 62 Issue 1 Pages 69-75
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 01, 2014
    JOURNALS FREE ACCESS
    Rituximab (RTX) is a monoclonal antibody that targets the B-cell-specific CD20 antigen. Recent reports indicate that RTX is effective against type 1 diabetes mellitus (T1DM) and hematologic as well as autoimmune diseases. Other studies have indicated that RTX therapy leads to the remission of recurrent or active Graves’ disease (GD). However, the efficacy of RTX in Japanese patients with autoimmune polyglandular syndrome (APS) has not been reported to date. Herein, we report the case of a patient with GD and T1DM with sustained endogenous insulin secretion capacity. To protect pancreatic β cells, we administered RTX at a dose of 500 mg (approximately 300 mg/m2) on 2 occasions 1 week apart. After treatment, no adverse effects were observed, and thyroid stimulating hormone receptor antibody (TRAb) was no longer detectable 4 months after RTX administration. In addition, the reduction in TRAb level improved thyroid function. Notably, the treatment induced remission over a period of 1 year after the diagnosis of GD.
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  • Mitsuyoshi Takahara, Toshihiko Shiraiwa, Taka-aki Matsuoka, Naoto Kata ...
    2015 Volume 62 Issue 1 Pages 77-86
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 17, 2014
    JOURNALS FREE ACCESS
    It remains to be seen whether pancreatic β cell dysfunction in type 2 diabetic patients can be ameliorated just by correcting hyperglycemia. The current pilot study investigated β cell function after a four-week treatment with a sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. Ten participants (age, 51 ± 13 years; hemoglobin A1c levels, 9.4 ± 1.0%) took 50 mg of ipragliflozin L-proline for four weeks and thereafter discontinued the agent for one week. A 75-g oral glucose tolerance test (OGTT) was performed at 0 (baseline), 4 (end of medication), and 5 weeks (end of washout). The β cell function was evaluated using the disposition index, which was calculated as the product of the ΔIns0-120/ΔGlu0-120 and the Matsuda index, where ΔIns0-120/ΔGlu0-120 represents the ratio of the incremental concentrations of insulin to those of glucose during the 0- to 120-min time period of the OGTT. The fasting glucose level was 182 ± 34 mg/dL at 0 week, 137 ± 20 mg/dL at 4 weeks (p < 0.001), and 154 ± 31 mg/dL at 5 weeks (p = 0.001). Compared to baseline, the disposition index was significantly elevated not only at 4 weeks (p < 0.001) but also at 5 weeks (p = 0.008). In conclusion, the current pilot study showed that the β cell function assessed by the OGTT-derived disposition index was significantly improved after a four-week treatment with ipragliflozin in Japanese patients with type 2 diabetes mellitus.
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  • Waka Yoshioka, Nobuyuki Amino, Akane Ide, Shino Kang, Takumi Kudo, Ei ...
    2015 Volume 62 Issue 1 Pages 87-92
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 10, 2014
    JOURNALS FREE ACCESS
    Infertile women sometimes associated with subclinical hypothyroidism (SCH). The guidelines of the American Endocrine Society, and American Association of Clinical Endocrinologists and American Thyroid Association recommend treatment with thyroxine (T4) for patients with SCH who want to have children. We examined 69 female infertile patients with SCH and the effects of levothyroxine (l-T4) therapy on pregnancy rates and pregnancy outcomes were observed. Fifty-eight (84.1%) patients successfully conceived during the T4 treatment period (Group A), although 17 patients (29.3%) had miscarriage afterward. The remaining 11 patients continued to be infertile (Group B). The median TSH value in Group A before the T4 treatment was 5.46 μIU/mL (range 3.1-13.3) and this significantly decreased to 1.25 μIU/mL (range 0.02-3.75) during the treatment (p < 0.001). The estimated duration of infertility before the T4 treatment was 2.8±1.7 years and the duration until pregnancy after the treatment was significantly shorter at 0.9±0.9 years (p < 0.001). Shortening of the infertile period after the T4 therapy was observed not only in patients who were treated with assisted reproductive technology (ART) but also in patients who conceived spontaneously in Group A. Administered T4 dose was 54.3±14.2 μg before pregnancy and 68.5±22.8 μg during pregnancy (p < 0.001). Anti-thyroid autoantibodies were identified in 42.0% of all patients and no significant difference was observed in positivity between Group A and Group B. High successful pregnancy rate and shorter duration of infertility until pregnancy after T4 treatment strongly suggest that T4 enhanced fertility in infertile patients with SCH.
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  • Kaoru Miyazaki, Fumie Miki, Sayaka Uchida, Hirotaka Masuda, Hiroshi Uc ...
    2015 Volume 62 Issue 1 Pages 93-99
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 12, 2014
    JOURNALS FREE ACCESS
    The objective of this study was to assess the potential predictive factors for follicle growth, ovulation, and pregnancy rate in patients with primary ovarian insufficiency/premature ovarian failure (POI/POF). We enrolled 25 POI patients with desired fertility who were treated and monitored for a minimum of 7 months between the years of 2000-2009 into this retrospective study. The clinical, endocrinologic, chromosomal, and autoimmunologic parameters of these patients were collected. Furthermore, hormonal backgrounds on each of 620 treatment cycles were investigated. The main outcome measures were follicle growth, ovulation, and pregnancy rate. Four of 25 patients (16%) conceived while being monitored and undergoing treatment. Follicle growth, ovulation, and pregnancy rate were not significantly different as a function of parity, iatrogenic history (e.g., chemotherapy), age of disease onset, serum estradiol (E2)/follicle stimulating hormone (FSH) level at the time of diagnosis, chromosomal abnormality, and positive autoantibody titer. The serum E2 levels on days 1-5 of withdrawal bleeding (Day 1-5 E2) were significantly higher in the cycles with successful follicle growth and ovulation than unsuccessful cycles (P < 0.05). Receiver-operator characteristic curve analysis revealed the cut-off value of the Day 1-5 E2 to be 15.5 pg/mL, and an area under the curve (AUC) value of 0.674 for follicle growth and 0.752 for ovulation. The results suggest that cycles with a Day 1-5 E2 ≥ 15.5 pg/mL have a higher rate of follicle growth and ovulation in patients with POI.
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  • Yuki Kawashima, Takeshi Usui, Masanobu Fujimoto, Naoki Miyahara, Rei N ...
    2015 Volume 62 Issue 1 Pages 101-106
    Published: 2015
    Released: January 30, 2015
    [Advance publication] Released: October 15, 2014
    JOURNALS FREE ACCESS
    Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is caused by mutations in the CYP21A2 gene. The residual enzyme activity is strongly associated with the phenotype. We describe a rare case of CAH with a rare CYP21A2 mutation. The patient was a one-year-old Japanese boy. At 16 days old, he was referred to our hospital because of elevated serum 17-OH-progesterone (17-OHP) levels in neonatal screening. The compound heterozygous mutations (IVS2-13 A/C>G, and p.E431K) in CYP21A2 were identified at 2 months old, and we diagnosed non-classical CAH, since he did not have significant physical signs (pigmentation and salt-wasting). However, his body weight decreased, and his serum 17-OHP level (99.5 ng/mL) was elevated at 3 months old. Steroid replacement therapy was started at 3 months old. Our patient’s clinical course resembled simple virilizing (SV) CAH, but classification was difficult because the patient showed increased renin activity indicating an aldosterone deficiency, and late onset of symptoms. While the IVS 2-13 A/C>G mutation is common in the classical form of CAH, p.E431K is a rare point mutation. Functional analysis revealed that the residual enzyme activity of p.E431L was 5.08±2.55% for 17-OHP and 4.12±2.37% for progesterone, which is consistent with SV CAH. p.E431 is localized in the L-helix near the heme-binding site. The mutation might interfere with heme binding, leading to deactivation of CYP21A2. This report showed that CYP21A2 p.E431 has an important effect on enzyme activity.
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