Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 54 , Issue 6
Showing 1-28 articles out of 28 articles from the selected issue
REVIEWS
  • Yoichi UETA, Hirofumi HASHIMOTO, Etsuro ONUMA, Yoh TAKUWA, Etsuro OGAT ...
    2007 Volume 54 Issue 6 Pages 831-838
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: September 07, 2007
    JOURNALS FREE ACCESS
    Download PDF (249K)
  • Atsushi KUMAGAI, Christoph REINERS, Valentina DROZD, Shunichi YAMASHIT ...
    2007 Volume 54 Issue 6 Pages 839-847
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: October 15, 2007
    JOURNALS FREE ACCESS
    One of the lessons from Chernobyl's legacy on health impact beyond 20 years is not only how to detect and treat the patients with radiation-associated thyroid cancers but how to follow up those who received radioactive iodine treatment repetitively after surgery in order to monitor any recurrence/worsening and also how to predict the risk of secondary primary cancers for their lifetime period. To evaluate the possibility of second primary tumors after radioactive iodine treatment, we reviewed the reports on risks from both external and internal radiation exposure, especially at high doses during childhood through an internet service of the National Library of Medicine and the National Institutes of Health, PubMed by the end of June, 2007, together with our own experience of Chernobyl childhood thyroid cancers. Children who were internally exposed after Chernobyl accident have a long-term risk of well differentiated thyroid cancers. Once they have disease, ironically radioactive iodine ablation is one of the useful therapies after surgical treatment. Elevated risks of solid cancers and leukemia have been found in radioiodine-treated patients, however, so far precious few reports from Chernobyl thyroid cancer patient were published. To reduce the adverse effects of radioactive iodine therapy on non-target tissues, recombinant human TSH has been applied and proved effective. Period of latency of second primary cancers may be very long. Therefore patients treated with high activities of radioactive iodine, especially children cases, should be carefully followed up during their whole lifespan.
    Download PDF (133K)
  • Fumiaki AOKI, Itaru KOJIMA
    2007 Volume 54 Issue 6 Pages 849-854
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: October 15, 2007
    JOURNALS FREE ACCESS
    Download PDF (132K)
ORIGINALS
  • Takafumi MAJIMA, Yasato KOMATSU, Akira SHIMATSU, Noriko SATOH, Atsushi ...
    2007 Volume 54 Issue 6 Pages 855-862
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: October 02, 2007
    JOURNALS FREE ACCESS
    It has been well established that raloxifene (RLX) has beneficial effects on bone primarily in Caucasian women. However, to date, there is a dearth of data for Japanese postmenopausal women. In this study, we prospectively evaluated the effects of RLX on bone and lipid metabolism in fifty Japanese postmenopausal patients with untreated osteoporosis. We measured bone mineral density (BMD) by dual-energy X-ray absorptiometry at 7 sites including the lumbar spine, femoral neck, and distal radius. BMD was significantly increased at the lumbar spine both at 6 months and at 12 months compared with at baseline (p<0.01 for both), although the possibility could not be completely excluded that this increase may be partly explained by an apparent increase induced by degenerative changes in lumbar vertebrae since we had no control subjects to compare and be more certain of the findings in this study. Both bone-specific alkaline phosphatase (BAP) and serum N-terminal telopeptide of type I collagen (NTx) significantly decreased both at 6 months (p<0.01 for both) and at 12 months (p<0.01 for both) compared with at baseline, but not below the lower limit of the reference value. Total cholesterol and low-density lipoprotein cholesterol were significantly improved while triglycerides and high-density lipoprotein cholesterol were unaltered. Although longer and larger studies with fracture endpoints are needed to draw definite conclusions, our findings suggest the favorable effects of RLX on bone and lipid metabolism in Japanese postmenopausal women with osteoporosis as in Caucasian women.
    Download PDF (276K)
  • Atsushi OGO, Tomoaki ETO, Shinsuke HIRAMATSU, Akimasa WATANABE, Yoshiy ...
    2007 Volume 54 Issue 6 Pages 863-870
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 14, 2007
    JOURNALS FREE ACCESS
    The patient, a 78-year-old female with a 10-year history of type 2 diabetes mellitus, was admitted to our department for evaluation of leg edema and general fatigue. Biochemical investigations revealed hypokalemia and elevated serum cortisol and plasma ACTH levels, with a loss of diurnal rhythm and failure of suppression at high doses (8 mg) of dexamethasone. No pituitary tumor or parasellar tumor was detected by contrast-enhanced computed tomography (CT) or magnetic resonance image scan of the pituitary. High resolution CT of the lung and bronchoscopic examination revealed no abnormalities. Abdominal and pelvic CT indicated bilateral, slightly diffuse, adrenal gland hyperplasia only. These findings led to a diagnosis of ACTH-dependent hypercortisolism from an undefined source. Ten days after admission the patient had a fever and was diagnosed with disseminated intravascular coagulation. Despite intensive treatment about 1 month after admission the patient died from progressive multiple organ failure. At autopsy, a histological examination of the periphery of the right middle lobe of the lung revealed the presence of tumorlets. Immunohistochemical staining of the tumorlets revealed scattered cells containing ACTH and many cells containing chromogranin A that were positive for Grimelius staining. In addition, multiple microabscesses were present throughout most tissues of the body. The ectopic hormonal production observed in the present case suggests that pulmonary tumorlets should thus be considered in the differential diagnosis of Cushing's syndrome, and medical treatment to inhibit steroidogenesis should be started immediately to reduce the risk of complications from hypercortisolism.
    Download PDF (2194K)
  • Michiaki FUKUI, Jintetsu SOH, Muhei TANAKA, Yoshihiro KITAGAWA, Goji H ...
    2007 Volume 54 Issue 6 Pages 871-877
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 12, 2007
    JOURNALS FREE ACCESS
    Low concentrations of endogenous androgens have been linked with insulin resistance and atherosclerosis. Men with diabetes have been reported to have lower serum testosterone concentration than non-diabetic men; however, there has never been a large study. The aim of this study was to investigate if endogenous androgen concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men, and to identify what factors may be associated with low serum testosterone concentrations in men with type 2 diabetes. Serum free testosterone concentrations were measured in 524 healthy men and in 331 consecutive Japanese men with type 2 diabetes between 40 and 69 years old. In addition, we investigated the relationships between serum free testosterone concentration and luteinizing hormone (LH) concentration as well as major cardiovascular risk factors including age, blood pressure, plasma lipid concentration, glycemic control (HbA1c), and BMI. Serum free testosterone concentrations were lower in men with type 2 diabetes than in healthy men in the 40-49 years group (10.9 ± 3.3 vs. 14.0 ± 3.6 pg/ml, P<0.0001), in the 50-59 years group (10.4 ± 3.2 vs. 12.1 ± 2.9 pg/ml, P<0.0001), and in the 60-69 years group (9.5 ± 2.6 vs. 10.5 ± 2.9 pg/ml, P = 0.0104). A negative correlation was found between serum free testosterone and LH concentrations (r = -0.326, P<0.0001). In conclusion, serum free testosterone concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men with each decade of life between 40 and 69 years old.
    Download PDF (214K)
  • Hu HUANG, Kaoruko TADA IIDA, Haruka MURAKAMI, Yoko SAITO, Takeshi OTSU ...
    2007 Volume 54 Issue 6 Pages 879-886
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 02, 2007
    JOURNALS FREE ACCESS
    Adiponectin is an adipocytokine that is involved in insulin sensitivity. The adiponectin gene contains a single nucleotide polymorphism (SNP) at position 276 (G/T). The GG genotype of SNP276 (G/T) is associated with lower plasma adiponectin levels and a higher insulin resistance index. Therefore, we examined the influence of SNP276 (G/T) on the plasma level of adiponectin in response to exercise training. Thirty healthy Japanese (M12/F18; 56 to 79 years old) performed both resistance and endurance training, 5 times a week for 6 months. The work rate per kg of weight at double-product break-point (DPBP) was measured. Blood samples were obtained before and after the experiment. Plasma concentrations of adiponectin, HbA1c, insulin, glucose, total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol, and triglyceride were measured. Genotypes of SNP276 were specified. Student's t-test for paired values and unpaired values was used. After the 6-month training period, the work rate per kg of weight at DPBP and the plasma HDL-cholesterol level were significantly improved (P<0.05), while no change was observed in the total plasma adiponectin level. However, the plasma adiponectin level in those with the GT + TT genotype had significantly increased (P<0.05). Additionally, the degree of the decrease in the HOMA-R level was significantly greater in the subjects with the GT + TT genotype than those with the GG genotype (p<0.05). Our results suggest that subjects with the genotype GT + TT at SNP276 (G/T) have a greater adiponectin-related response to exercise training than those with the GG genotype.
    Download PDF (176K)
  • Tomoko SANTOH, Mikio WATANABE, Shoko KURODA, Daishi UEDA, Yoshinori IW ...
    2007 Volume 54 Issue 6 Pages 887-894
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 12, 2007
    JOURNALS FREE ACCESS
    Peripheral immunoglobulin (Ig) G3-secreting cells and serum concentrations of interleukin (IL)-10, a class-switching factor to IgG3-secreting cells, increase in patients with intractable Graves' disease (GD). However, they are not practical for laboratory tests. To find more stable and easily detectable markers of disease intractability or disease severity in patients with GD or Hashimoto's disease (HD), we examined the serum concentration of IgG3 in 58 euthyroid GD patients who had been undergoing antithyroid drug treatment for more than 5 years but still must continue drug treatment to maintain a euthyroid state (intractable GD), 26 GD patients who had maintained a euthyroid state for more than 2 years without any treatment (GD in remission), 20 untreated, thyrotoxic GD patients, 40 euthyroid HD patients treated with thyroxine (5 men and 35 women), 13 untreated, euthyroid HD patients, and 39 healthy volunteers. Serum concentrations of IgG3 increased in euthyroid patients with intractable GD and in those with GD in remission, but serum concentrations of IgG were not altered. The ratio of serum concentrations of IgG3 to total IgG (IgG3/IgG ratio) was higher in euthyroid patients with intractable GD than in those with GD in remission. Multiple logistic-regression analysis demonstrated that IgG3/IgG ratio and goiter size were independent factors in disease intractability of GD patients. These results suggest that IgG3/IgG ratio and goiter size may be used as independent markers associated with GD intractability.
    Download PDF (224K)
  • Hiroaki UENO, Tomomi SHIIYA, Masanari MIZUTA, Muhtashan MONDAL, Masami ...
    2007 Volume 54 Issue 6 Pages 895-902
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 16, 2007
    JOURNALS FREE ACCESS
    Ghrelin is an acylated 28-amino-acid peptide that stimulates food intake, GH secretion, and gastric motility. Experimental studies have suggested that ghrelin plays roles in glucose homeostasis, atherosclerosis, and microangiopathy. We investigated possible involvement of ghrelin in micro- and macro-vascular diabetic complications and glycemic control in diabetic patients. Fasting and postprandial plasma ghrelin concentrations after a test meal were measured in 108 and 61 Japanese diabetic patients, respectively. Plasma ghrelin concentrations were negatively correlated with body mass index (BMI) (r = -0.309, P = 0.002) or HbA1c (r = -0.264, P = 0.0065). Plasma ghrelin levels in patients with diabetic nephropathy who showed high serum creatinine levels (s-Cre) were significantly higher than those in patients who showed normal s-Cre (P<0.02). In patients with diabetic triopathy, plasma ghrelin concentrations were significantly lower than those in patients without diabetic complications (P<0.05). Stepwise multiple regression analyses revealed that s-Cre, BMI, and HbA1c were independently associated with plasma ghrelin levels. A postprandial decrease of ghrelin was observed in patients with normal CVR-R values or those with normal body weight, whereas it was not seen in obese patients or in patients with low CV R-R values. Suppression rates of ghrelin 30-60 min after a test meal in obese patients were significantly lower than those in normal-weight patients. These findings suggest that ghrelin secretion is suppressed by long-term hyperglycemia and that obesity influences the regulation of ghrelin secretion.
    Download PDF (334K)
  • Takashi ASANO, Ryoko YOSHIDA, Hideaki OGATA, Kazuhiko KOKAWA, Masao OG ...
    2007 Volume 54 Issue 6 Pages 903-910
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 16, 2007
    JOURNALS FREE ACCESS
    Determinants of glucose intolerance were studied in 163 obese Japanese young adults, 18 to 21 years old (43 females,120 males), who underwent 75-g oral glucose tolerance testing. Type 2 diabetes was newly diagnosed in 2.9% (n = 4); impaired fasting glucose (IFG) in 5.1% (n = 7); and impaired glucose tolerance (IGT) in 10.9% (n = 15). A homeostasis model assessment of insulin resistance (HOMA-IR) was used to estimate insulin sensitivity; β-cell function during the first 30 min of the test was measured and defined as the insulinogenic index. This index was adjusted for insulin sensitivity, since this affects both β-cell function and glucose disposition (disposition index). The relationship between insulinogenic index and 1/HOMA-IR was not hyperbolic. However, the disposition index (DI) was useful for the estimation of β-cell function with the correct confirmation about it validity using β-cell function index (BI). The association between insulin sensitivity and β-cell function to glucose disposal, as measured by the area under the glucose curve (AUCg), was examined in all subjects. Insulin sensitivity was significantly related to AUCg (log HOMA-IR; R 2 = 0.142, p<0.0001). On the other hand, an inverse curvilinear relationship was observed between β-cell function and AUCg (log(ΔI/ΔG)/HOMA-IR, R 2 = 0.411, p<0.0001). Thus, impaired β-cell function, when estimated as DI, was strongly associated with impaired glucose disposal. In conclusion, our study showed that both insulin sensitivity and impaired β-cell function are associated with impaired glucose metabolism, and that β-cell function may be more important in determining glucose disposal.
    Download PDF (228K)
  • Masamichi KUWAJIMA, Hiroaki FUJIHARA, Hiroyoshi SEI, Asako UMEHARA, Ma ...
    2007 Volume 54 Issue 6 Pages 911-925
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 16, 2007
    JOURNALS FREE ACCESS
    The mechanism of onset of hypoglycemia in patients with carnitine deficiency has yet to be determined. Using mice with systemic carnitine deficiency (JVS mice), we examined this mechanism, focusing on the weaning period (days 14-28 postpartum). For normal mice, the survival rate was 100%, and no hypoglycemia was observed at all. Gastric lactose began to decrease on day 17, and cellulose increased sharply in amount thereafter. For JVS mice, the survival rate was 77% on day 14 and 28% on day 28. From day 21 on, hypoglycemia was noted. Gastric lactose had disappeared almost completely by day 17, and cellulose was almost undetectable from days 14 to 28. Expression of orexin mRNA in the hypothalamus did not differ between JVS and normal mice on day 14, but was suppressed in JVS mice on days 21 and 28. When JVS mice were fed a carnitine-rich diet, suppression of expression of orexin mRNA in hypothalamus was eliminated, and on day 28 lactose and cellulose were detected in the stomach without hypoglycemia. In conclusion, the suppression of the expression of orexin in the hypothalamus during the weaning period may be involved in the marked anorexia in JVS mice, which eventually leads to death from hypoglycemia.
    Download PDF (1129K)
  • Eijun NISHIHARA, Yuji NAGAYAMA, Nobuyuki AMINO, Akira HISHINUMA, Toru ...
    2007 Volume 54 Issue 6 Pages 927-934
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 16, 2007
    JOURNALS FREE ACCESS
    Constitutively activating germline mutations of the thyrotropin receptor (TSHR) gene have been identified as a molecular cause of hereditary nonautoimmune hyperthyroidism. We describe here a Japanese kindred with two affected individuals who showed overt hyperthyroidism and mild goiter in the absence of TSHR antibodies. A novel heterozygous germline point mutation, identified in both individuals, resulted in an amino acid substitution of aspartic acid for tyrosine at codon 617 (Asp617Tyr) in the third intracellular loop of the TSHR. Screening of 7 additional family members led to the identification of the same mutation in 4 relatives: 1 had undergone thyroidectomy due to hyperthyroidism but 3 were asymptomatic with subclinical hyperthyroidism. In vitro functional studies of the Asp617Tyr TSHR demonstrated a constitutive activation of the cyclic adenosine monophosphate pathway, but not of the inositol phosphate cascade, with data similar to those of Asp619Gly, the first constitutively activating mutant TSHR identified. Treatment with inorganic iodine for 7 months successfully relieved all symptoms of hyperthyroidism in both patients.
    Download PDF (326K)
  • Ippei KANAZAWA, Masahiro YAMAMOTO, Toru YAMAGUCHI, Mika YAMAUCHI, Shoz ...
    2007 Volume 54 Issue 6 Pages 935-940
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 30, 2007
    JOURNALS FREE ACCESS
    The relationship between osteoporosis and magnesium (Mg) deficiency is still controversial. Here we report a case of an 82-year-old woman with a giant adenomatous goiter and severe osteoporosis with multiple vertebral fractures, whose clinical course indicated that her osteoporosis was probably due to Mg deficiency. She visited our hospital for treatments of tetany. Laboratory data showed the existence of hypomagnesemia, hypocalcemia, hypokalemia, vitamin D deficiency, and slightly elevated intact PTH. Intravenous administration of Mg not only improved these electrolyte abnormalities but also increased serum levels of intact PTH, bone formation markers, 1,25-dihydroxyvitamin D, as well as bone resorption markers in the urine, and lowered urinary phosphate reabsorption. Hypomagnesemia on admission seemed to arise from long-lasting poor food intake and malnutrition, because it improved after the disappearance of dysphagia with a goiter resection. After the operation, BMD values at the lumbar spine and femoral neck obviously increased during 6 months of Mg supplementation without any specific therapies for osteoporosis. Mg deficiency in this case seemed to cause impaired secretion of PTH from the parathyroid and the refractoriness of bone and kidney to the hormone, which led to the suppression of both bone remodeling and renal vitamin D production. These processes were probably linked to her severe osteoporosis, which was reversed by Mg supplementation.
    Download PDF (284K)
  • Toshihiro TAJIMA, Fumie FUJIWARA, Akira SUDO, Shinji SAITO, Kenji FUJI ...
    2007 Volume 54 Issue 6 Pages 941-944
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 14, 2007
    JOURNALS FREE ACCESS
    We encountered a Japanese patient of congenital hypothyroidism with severe cerebellum atrophy. The boy was born after 40 weeks of gestation by normal vaginal delivery from nonconsanguineous parents. There were no abnormal physical findings; however neonatal mass screening for congenital hypothyroidism at 5 days of age demonstrated elevated thyrotropin (TSH) level (15.5 μU/ml, normal range 0.54-10.0 μU/ml). He was suspected to have subclinical or mild congenital hypothyroidism (CH). Thus he was treated with L-thyroxine using a regimen that rendered his serum TSH concentration within normal range from 27 days of age. Despite early and adequate treatment, he showed signs of global developmental delay and became gradually hypotonic and exhibited a staggering gait at 3 years of age. Brain magnetic resonance imaging (MRI) demonstrated marked cerebellar atrophy with an intact brainstem. Thyroidal uptake of radioiodide and thyroid gland size were normal, indicating a functional defect only. The relation between congenital hypothyroidism and severe cerebellar atrophy in our patient is not clear. As only a few cases of the combination of CH and cerebellar anomalies have been described previously, cerebellar symptoms in CH should be examined carefully.
    Download PDF (210K)
  • Hiroko MISE, Shigeo YURA, Hiroaki ITOH, Mercy A. NUAMAH, Maki TAKEMURA ...
    2007 Volume 54 Issue 6 Pages 945-951
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 14, 2007
    JOURNALS FREE ACCESS
    Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and ΔSD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and ΔSD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.
    Download PDF (341K)
  • Rina OHWADA, Mari HOTTA, Kanji SATO, Tamotsu SHIBASAKI, Kazue TAKANO
    2007 Volume 54 Issue 6 Pages 953-959
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 12, 2007
    JOURNALS FREE ACCESS
    Osteoporosis is one of the major complications in anorexia nervosa (AN) patients. Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) have been identified as important regulators of bone turnover. The objective of this study was to clarify the role of RANK-RANKL-OPG system, and their relationship with other regulators for bone metabolism in AN patients. We investigated serum levels of RANKL, OPG, and bone turnover markers of 26 Japanese young female AN patients and 7 age-matched healthy women. We measured serum levels of estradiol (E2), insulin like growth factor-I (IGF-I) and triiodothyronin (T3) from the same samples and studied their relationship with RANKL or OPG. Mean serum levels of E2, IGF-I, T3 and leptin in AN patients were significantly lower than those of controls (p<0.05). Serum levels of OPG in AN patients were significantly higher than those in controls and negatively correlated with body mass index (BMI), E2, IGF-I or leptin. Serum levels of free RANKL could not be detected except for only one healthy control in both groups. These results suggest that serum OPG levels may be increased by a compensatory mechanism for malnutrition and estrogen deficiency which induces an increase in bone resorption.
    Download PDF (227K)
  • Kazunori KAGEYAMA, Hidetoshi IKEDA, Takeshi NIGAWARA, Satoru SAKIHARA, ...
    2007 Volume 54 Issue 6 Pages 961-968
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: December 04, 2007
    JOURNALS FREE ACCESS
    We describe here a case of a clinically nonfunctioning pituitary adenoma, but with expression of ACTH and PRL. A 42-year-old woman was referred to our department for further evaluation of pituitary tumor. She had no acromegaloid features, and no typical Cushingoid features. She had no galactorrhea, and had regular menses. GH, IGF-I, LH, FSH, TSH, ACTH and cortisol levels in blood were all within the normal ranges, while PRL levels were mildly elevated. Both ACTH and cortisol levels were adequately increased in response to CRH, and both were suppressed by a small dose of dexamethasone. Plasma ACTH and cortisol levels were decreased at night, suggesting the circadian rhythms for plasma ACTH levels were undisturbed. Based on these findings we did not clinically suspect ACTH-producing tumor, however immunohistochemistry revealed ACTH immunoreactivity in the pituitary adenoma. Therefore, the tumor was considered a silent corticotroph adenoma. PRL was co-expressed in a significant subpopulation of ACTH-immunoreactive tumor cells. Ptx1, Neuro D1, and T pit were densely expressed and Pit-1 was sparsely expressed in the nuclei of adenoma cells. It is therefore possible that a tumor originating in an immature or uncommited adenohypophysial stem cell may later differentiate into different cell types due to a combination of certain specific transcriptional factors.
    Download PDF (1389K)
  • Ryo KODERA, Fumio OTSUKA, Kenichi INAGAKI, Tomoko MIYOSHI, Toshio OGUR ...
    2007 Volume 54 Issue 6 Pages 969-974
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 02, 2007
    JOURNALS FREE ACCESS
    A 46-year-old Japanese male with hypertension was referred for examination of left adrenal tumor incidentally detected by computed tomography (CT) scan. The patient had a 4-month history of hypertension. Abdominal CT demonstrated a low-density mass 2.5 cm in diameter in the left adrenal region that was observed as a high-intense lesion with T2-weighted magnetic resonance imaging. 131 I-adosterol scintigraphy showed normal uptake of bilateral adrenals. The adrenocortical hormone levels were within normal ranges; however, urinary noradrenaline excretion was slightly elevated, likely due to concurrent sleep apnea syndrome. Based on the observation of a very tiny bubble in the ventral portion of the adrenal mass by careful review of CT images examined at a previous hospital, a restudy of abdominal CT with oral contrast was performed. In this restudy abdominal CT we observed positive enhancement of the left adrenal mass, indicating that the adrenal mass was a diverticulum derived from posterior gastric fornix. The present case study reinforces that preoperative differentiation from mimic adrenal tumors is necessary in cases of cystic adrenal mass in the left adrenal region.
    Download PDF (1565K)
  • Yoshie KANAZAWA, Yasuhiro IGARASHI, Koji KOMIYA, Yuko SAKURAI, Tomoaki ...
    2007 Volume 54 Issue 6 Pages 975-983
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 14, 2007
    JOURNALS FREE ACCESS
    To assess and compare the efficacy and safety of insulin glargine as intensive replacement of basal insulin in Japanese patients with type 1 (n = 72) and type 2 (n = 46) diabetes, we switched their intensive insulin regimen from NPH plus regular or rapid-acting insulin to glargine plus bolus insulin, which included regular and rapid-acting insulin, and recorded changes in glycemic control and frequency of hypoglycemia for 18 months. The dose titration of basal and bolus insulin was based on home self-monitored blood glucose measurements and monthly HbA1C. Mean HbA1C level was improved significantly at 3 months after switching to glargine plus bolus insulin regimen and these effects continued for 18 months in both type 1 and type 2 diabetes patients (HbA1C level: type 1: baseline 8.9 ± 2.6%, 18 months 7.8 ± 1.5% (p<0.05), type 2: baseline 8.2 ± 2.6%, 18 months 7.7 ± 1.5%. Body weight was slightly but significantly increased at 18 months only in type 2 diabetes. Total daily bolus insulin doses were not changed but basal insulin could be increased significantly after switching regimens in both types diabetes compared with baseline. The frequency of mild to moderate hypoglycemia (self-assisted episodes, blood glucose <70 mg/dl) was marginally lower with glargine but not significantly. Self-monitored fasting blood glucose level was significantly improved after switching in type 2 diabetes. Patients with the worst HbA1C level at baseline exhibited more than 10% improvement in HbA1C level after switching both type 1 and type 2 diabetes. The HbA1C levels of the effectively treated patients were comparable to those of ineffectively treated ones at 6 months and the same improvement was seen at 18 months. Our results suggested that insulin glargine is more effective than NPH insulin as intensive replacement of basal insulin, particularly in those Japanese patients with difficult glycemic control with NPH insulin, equally in both type 1 and type 2 diabetes.
    Download PDF (355K)
  • Pinar ISGUVEN, Ilknur ARSLANOGLU, Melih EROL, Metin YILDIZ, Erdal ADAL ...
    2007 Volume 54 Issue 6 Pages 985-990
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 12, 2007
    JOURNALS FREE ACCESS
    The aim of the present study is to investigate possible alterations in ghrelin and other hormone levels related to appetite and somatic growth in children with iron deficiency anemia. Twenty-five patients and 25 healthy controls that were prepubertal and within normal limits regarding height and BMI standard deviation scores were recruited. Ghrelin, leptin, IGF-I, IGFBP-3, insulin, thyroid hormones and cortisol levels were studied. Ghrelin, insulin and IGF-I levels were significantly low in the study group (ghrelin 13.58 ± 16.32 vs. 35.39 ± 23.69 ng/ml, p<.001; insulin 3.41 ± 2.42 vs. 5.67 ± 1.09 mU/ml, p = .008 and IGF-I 126.94 ± 92.82 vs. 203 ± 105.1 ng/ml, p = .015). We concluded that low ghrelin and insulin levels might be causes of the appetite loss in iron deficiency and as a result of appetite loss and undernutrition as well as by direct effects they might be related with growth retardation, which could be also influenced by low IGF-I levels.
    Download PDF (133K)
  • Kai-Fuan YEO, Yi-Sun YANG, Kuo-Shuen CHEN, Chiung-Huei PENG, Chien-Nin ...
    2007 Volume 54 Issue 6 Pages 991-993
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 30, 2007
    JOURNALS FREE ACCESS
    Although many cases of simultaneous presentation of thyrotoxicosis (thyroid storm) and diabetic ketoacidosis have been reported, it is a clinically unusual situation and remains a diagnostic and management challenge in clinical practice. The diagnosis of diabetic ketoacidosis or thyrotoxicosis may be masked leading to serious complications. We report two patients with simultaneous thyrotoxicosis and diabetic ketoacidosis resulted in sudden cardiac arrest, emphasizing early recognition and prompt treatment when these two disease are presented concomitantly.
    Download PDF (100K)
  • Eun-Jung RHEE, Sang-Tai HWANG, Won-Young LEE, Ji-Ho YOON, Byung-Jin KI ...
    2007 Volume 54 Issue 6 Pages 995-1002
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: December 04, 2007
    JOURNALS FREE ACCESS
    Plasma total homocysteine (tHcy) is an independent risk factor for cardiovascular disease and increased tHcy levels have been reported to be a novel risk factor of atherosclerotic disease. The aim of this study was to assess the association of the metabolic syndrome components with plasma (tHcy) level. Total 722 participants (284 men, 438 women) from the medical checkup program were enrolled in this study. The clinical characteristics and biochemical parameters of the subjects were assessed and the tHcy levels were compared according to the components of metabolic syndrome diagnosed by Adult Treatment Panel (ATP) III guideline and International Diabetes Federation (IDF) criteria. Among the components, groups with larger waist circumference and higher fasting blood glucose levels showed significantly higher tHcy level than the counterparts. Although statistically insignificant, mean concentrations of tHcy was higher in subjects with metabolic syndrome defined by both criteria. In multiple regression analysis, age, sex and systolic blood pressure were the independent determinants of tHcy level. In conclusion, tHcy level was not associated with metabolic syndrome defined by either criteria in Korean subjects.
    Download PDF (126K)
  • Masanori ADACHI, Yumi ASAKURA, Yoshiaki SATO, Toshihiro TAJIMA, Takeo ...
    2007 Volume 54 Issue 6 Pages 1003-1007
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 12, 2007
    JOURNALS FREE ACCESS
    Bartter syndrome (BS) type 1, also referred to antenatal BS, is a genetic tubulopathy with hypokalemic metabolic alkalosis and prenatal onset of polyuria leading to polyhydramnios. It has been shown that BS type 1 is caused by mutations in the SLC12A1 gene encoding bumetanide-sensitive Na-K-2Cl - cotransporter (NKCC2). We had the opportunity to care for two unrelated Japanese patients of BS type 1 with typical manifestations including polyhydramnios, prematurity, hypokalemia, alkalosis, and infantile-onset nephrocalcinosis. Analysis of the SLC12A1 gene demonstrated four novel mutations: N117X, G257S, D792fs and N984fs. N117X mutation is expected to abolish most of the NKCC2 protein, whereas G257, which is evolutionary conserved, resides in the third transmemebrane domain. The latter two frameshift mutations reside in the intra-cytoplasmic C-terminal domain, which illustrates the importance of this domain for the NKCC2 function. In conclusion, we found four novel SLC12A1 mutations in two BS type 1 patients. Development of effective therapy for hypercalciuria is mandatory to prevent nephrocalcinosis and resultant renal failure.
    Download PDF (389K)
  • Kazutaka AOKI, Hideaki KATO, Yasuo TERAUCHI
    2007 Volume 54 Issue 6 Pages 1009-1014
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 30, 2007
    JOURNALS FREE ACCESS
    We recently demonstrated that administration of miglitol at 15 min after the start of a meal decreased the area under the curve (AUC) of plasma glucose, similar to the observation following its administration just before a meal. This finding prompted us to examine whether a divided-dose regimen of miglitol might attenuate postprandial glucose excursions even more effectively. We, therefore, examined several schedules of miglitol administration in 15 healthy men. Miglitol was administered by four different schedules in each subject (control: no miglitol, intake 1: drug administered just before a meal (50 mg); intake 2: drug administered at 15 min after the start of a meal (50 mg); intake 3: drug administered in two divided doses: just before a meal (25 mg) and at 15 min after the start of a meal (25 mg). The AUC of glucose excursions, defined as increment above the fasting glucose level, (AUC0-180 min of glucose excursions) was significantly reduced as compared with that in the control condition after miglitol administration by intake schedule 3, while this parameter showed a tendency towards decrease after the drug administration by intake schedules 1 and 2. The AUC0-180 min of the serum insulin level was also significantly decreased for all the intake schedules of miglitol, as compared with that in the control condition. Thus, administration of miglitol in two divided doses appeared to be the most suitable for obtaining effective regulation of postprandial glucose excursions in healthy men. This result may suggest that the divided-dose administration regimen may also be effective in diabetic patients.
    Download PDF (333K)
NOTES
  • Ken-ichi KASHIMADA, Toshikazu ONISHI, Makoto ONO, Kentaro MIYAI, Masay ...
    2007 Volume 54 Issue 6 Pages 1015-1019
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 14, 2007
    JOURNALS FREE ACCESS
    Transient growth hormone deficiency (GHD) is occasionally found in prepubertal individuals, and this phenomenon has been variously interpreted. Sex steroids enhance GH secretion; however, the cut-off values of provocative GH tests are not modified according to the physiological changes. Physiological changes in sex steroid levels are thought to cause the image of transient GHD. In addition, the reproducibility of provocative GH tests makes the interpretation complicated. We experienced a case of a boy with short stature who had undergone provocative GH tests at three different times: childhood (5 and 7 years old), before puberty (12 years old), and in adolescence (15 years old). Although the responses of GH in his childhood and adolescence were within the normal range, his prepubertal GH response was extremely low, as if he had "complete" GHD (peak GH: insulin test, 0.60 ng/ml; clonidine test, 0.78 ng/ml). No morphological changes were observed in the pituitary gland or hypothalamus on MRI. The level of insulin-like growth factor 1 was in the normal range for his age at this time. Here, we report the clinical course and endocrinological data of this case, and suggest that transient GHD is caused not only by the physiological effects of sex steroids but also by certain mechanisms that actively reduce GH secretion.
    Download PDF (252K)
  • Takashi SHINAGAWA, Reiko HORIKAWA, Tsuyoshi ISOJIMA, Yasuhiro NAIKI, T ...
    2007 Volume 54 Issue 6 Pages 1021-1025
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: November 30, 2007
    JOURNALS FREE ACCESS
    Since 1989, neonatal mass screening for congenital adrenal hyperplasia (CAH) has been carried out in Japan. The mass screening has detected not only the patients with the classic form of steroid 21-hydroxylase deficiency (21-OHD), but also those with the nonclassic (NC) form of 21-OHD, and the molecular basis in these patients has been elucidated. However, the homozygous V281L mutation in CYP21A2, the common mutation in the NC form in Caucasians, has not been described in Japanese patients, implying at least two possibilities; 1) the V281L mutation itself might be very rare in Japanese, and 2) nonclassic 21-OHD patients bearing the V281L mutation might be barely detectable by the mass-screening program, hence overlooked in Japan. In the present study, we describe a Brazilian girl with the NC form of 21-OHD, who was pointed out to have mildly elevated 17α-hydroxyprogesterone in blood by the mass screening in Japan. Genetic analysis revealed that the patient was homozygous for the V281L mutation, and that the parents were heterozygous for the V281L mutation. Thus, the NC patients due to the homozygous V281L mutation can be detectable by the mass-screening program for CAH in Japan, and further accumulation and analysis of the NC patients should elucidate the frequency of the V281L allele in Japan.
    Download PDF (214K)
RAPID COMMUNICATION
  • Atsuko KUROKAWA, Kosuke AZUMA, Tomoya MITA, Yukiko TOYOFUKU, Yoshio FU ...
    2007 Volume 54 Issue 6 Pages 1027-1031
    Published: 2007
    Released: February 20, 2008
    [Advance publication] Released: September 08, 2007
    JOURNALS FREE ACCESS
    2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with no affinity for estrogen receptors. It inhibits cell proliferation, thus is a potentially useful drug to block the progression of atherosclerosis. As a first step to examining the anti-atherosclerotic effects of 2-ME, we investigated monocyte adhesion to aortic endothelial cells, which is considered a prerequisite to atherosclerosis in vivo. Eight-week-old Sprague-Dawley rats were ovariectomized then treated by slow-release pellets with placebo, 17-β-estradiol (5 μg/day), low-dose 2-ME (10 μg/day), or high-dose 2-ME (100 μg/day). After 6 weeks, enface analysis showed an increased number of monocytes adhering to endothelial cells of the thoracic aorta in ovariectomized rats compared with sham-operated controls. This increase was predominantly inhibited by treatment with 17β-estradiol, and low-dose or high-dose 2-ME. The observed effects were unrelated to changes in serum lipids, blood glucose, or blood pressure. Our data suggested that 2-ME mediates the anti-atherosclerotic actions of estradiol at least in part by preventing monocyte adhesion to the aortic endothelium.
    Download PDF (139K)
LETTER TO THE EDITOR
feedback
Top