Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Volume 58 , Issue 5
Showing 1-12 articles out of 12 articles from the selected issue
ORIGINALS
  • Akira Shimatsu, Shigeru Tai, Toshiaki Tanaka, Kenji Fujieda, Akira Ter ...
    2011 Volume 58 Issue 5 Pages 325-333
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 05, 2011
    JOURNALS FREE ACCESS
    The clinical characteristics of Caucasian adults with growth hormone (GH) deficiency (GHD) have been well defined. However, no large-scale clinical practice study has examined the clinical characteristics of Japanese adults with GHD. The aim of our study was to describe the clinical characteristics of Japanese adults with GHD by reviewing the records of participants who were GH-naive at the time of enrollment in the Hypopituitary Control and Complications Study (N = 349). The majority of participants (280 of 349; 80.2%) had adult-onset rather than childhood-onset GHD. Hypothalamo-pituitary tumors were the most common cause of GHD in Japanese adults (247 of 349; 70.8%); these tumors were primarily pituitary adenomas in participants with adult-onset GHD (156 of 243; 64.2%), and germ cell tumors (19 of 40; 47.5%) and craniopharyngiomas (18 of 40; 45.0%) in participants with childhood-onset GHD. Most participants (310 of 349; 88.8%) had multiple pituitary hormone deficiencies. Dyslipidemia (195 of 349; 55.9%), visual field loss (67 of 349; 19.2%), hypertension (59 of 349; 16.9%), and liver disease (54 of 349; 15.5%) were the most common pre-existing conditions in Japanese adults with GHD. Quality of life was decreased in seven of the eight short form-36 domains in participants with GHD compared with age- and sex-matched healthy Japanese individuals. Our findings confirm that the clinical characteristics of Japanese adults with GHD are similar to those of Caucasian adults with GHD. Confirmation of these clinical characteristics will enhance the ability of clinicians to identify and treat Japanese adults with GHD.
    Download PDF (1005K)
  • Tomomi Shiiya, Hiroaki Ueno, Koji Toshinai, Takashi Kawagoe, Seiko Nai ...
    2011 Volume 58 Issue 5 Pages 335-342
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: March 19, 2011
    JOURNALS FREE ACCESS
    Ghrelin, an acylated peptide produced predominantly in the stomach, stimulates feeding and growth hormone (GH) secretion via interaction with the GH secretagogue receptor. Ghrelin molecules are present in two major endogenous forms, an acylated form (ghrelin) and a des-acylated form (des-acyl ghrelin). Recent studies indicated that aerobic exercise did not change plasma total ghrelin levels, however, dynamics of circulating ghrelin and des-acyl ghrelin during aerobic exercise remains unclear. The purpose of this study is to examine the effects of moderate intensity exercise on plasma ghrelin and des-acyl ghrelin concentrations, and to investigate the relationship between ghrelin molecules and other hormonal and metabolic parameters during exercise. Nine healthy males (25.2 ± 0.5 years) exercised for 60 min at 50% of their maximal oxygen consumptions. We measured the plasma concentrations of ghrelin, des-acyl ghrelin, GH, norepinephrine (NE), epinephrine (E), dopamine (DA), insulin, and glucose. Plasma ghrelin level significantly decreased during exercise, whereas plasma des-acyl ghrelin and total ghrelin levels did not change. Plasma NE, E, DA and GH levels were significantly increased during exercise. Plasma insulin level significantly decreased during exercise, and plasma glucose levels remained steady during exercise. NE, E, DA, and GH were correlated negatively with plasma ghrelin levels. These findings suggest that acute moderate exercise may suppress ghrelin release from the stomach, decrease ghrelin O-acyltransferase activity, and/or activate ghrelin utilization in peripheral tissues and that exercise-induced ghrelin suppression may be mediated by activated adrenergic system.
    Download PDF (1116K)
  • Ai Yoshihara, Jaeduk Yoshimura Noh, Ayako Nakachi, Hidemi Ohye, Shiori ...
    2011 Volume 58 Issue 5 Pages 343-348
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: March 17, 2011
    JOURNALS FREE ACCESS
    Thyroid-associated orbitopathy (TAO) is characterized by immune-mediated inflammation of the extraocular muscles surrounding orbital connective tissue and adipose tissue. Severe orbitopathy related to autoimmune thyroid disease often occurs in patients with Grave’s disease, but it is rare in patients with Hashimoto’s thyroiditis. The pathogenesis of TAO is unclear. Several studies have noted a strong correlation between the levels of antibodies to thyrotropin receptor antibody (TRAb) and TAO in Graves’ disease. Mild upper eyelid retraction has been reported to be common in Hashimoto’s thyroiditis patients, however severe orbitopathy is rare. We report two cases of severe TAO in patients with Hashimoto’s thyroiditis who required systemic glucocorticoid therapy and orbital irradiation to treat the TAO. The activity of the TAO was high in both patients, because their clinical activity scores (CAS) for the orbitopathy were high, and magnetic resonance imaging (MRI) showed enlargement of the extraocular muscles and an increase in T2 signal intensity and prolonged T2 relaxation time which indicate an active stage of inflammation. We tested the presence of TRAb by three different assays and were negative in both patients. Since the eye muscle damage cannot be due to TSH receptor antibodies, other pathogenetic mechanisms may be responsible for the orbitopathy in patients with Hashimoto’s thyroiditis.
    Download PDF (891K)
  • Esat Erdem Türemen, Berrin Çetinarslan, Tayfun Sahin, Zeyn ...
    2011 Volume 58 Issue 5 Pages 349-354
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 14, 2011
    JOURNALS FREE ACCESS
    The relationship betweeen subclinical hypothyroidism (SH) and cardiovascular disease has been one of the most popular topics recently. There is still some controversy concerning its cardiovascular impact and management protocols. Our study aims to investigate the presence of the well known preceding clinical situations of atherosclerosis like endothelial dysfunction and inflammation in subclinical hypothyroidism. Thirty-seven patients with subclinical hypothyroidism (29 women, 8 men) and 23 healthy volunteers (19 women, 4 men) were recruited for the study. Endothelial dysfunction was measured by examining brachial artery responses to endothelium-dependent (flow mediated dilation, FMD) and endothelium-independent stimuli (sublingual nitroglycerin (NTG)). Serum TNF-alpha, interleukin-6, and hs-CRP were measured. The estimate of insulin resistance by HOMA score was calculated with the formula: fasting serum insulin (μIU/mL) x fasting plasma glucose (μM/L) / 22.5. There were no significant differences in age, body mass index, waist circumference, HOMA scores. There was a statistically significant difference in endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) between the patients with subclinical hypothyroidism and the normal healthy controls. The groups were well matched for baseline brachial artery diameter. The TSH and LDL, IL-6, TNF-alpha and hs-CRP levels in the patient group were significantly higher than those in control group. A positive correlation was found only between endothelium-dependent vasodilation and TNF-alpha, hs-CRP and IL-6, TSH, total cholesterol, LDL and triglycerides. Endothelium-independent vascular response was not correlated with any of the metabolic or hormonal parameters. Neither of the groups were insulin resistant and there was not any difference either in fasting insulin or in glucose levels. We found endothelial dysfunction in subclinical hypothyroidism group. Endothelium-dependent (FMD) and endothelium-independent vascular responses (NTG) were lower in patient group. Our findings suggest that there is endothelial dysfunction and low grade chronic inflammation in SH due to autoimmune thyroiditis. There are several contributing factors which can cause endothelial dysfunction in SH such as changes in lipid profile, hyperhomocysteinemia. According to our results low grade chronic inflammation may be one of these factors.
    Download PDF (741K)
  • Kaiming Huo, Zhan Zhang, Dehua Zhao, Hezhou Li, Jun Wang, Xinxia Wang, ...
    2011 Volume 58 Issue 5 Pages 355-361
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 05, 2011
    JOURNALS FREE ACCESS
    Neurodevelopment in children with congenital hypothyroidism who receive early treatment is generally good. However, subtle neurological deficits still exist in some patients. The aim of this investigation was to evaluate factors that may influence neurodevelopmental outcome in congenital hypothyroidism patients. The developmental quotient (DQ) of 155 children with congenital hypothyroidism was evaluated at 24 months of age, using Gesell Developmental Schedules (GDS), and compared with that of 310 healthy controls. Mean DQ scores in congenital hypothyroidism patients were 7.5 points lower for adaptive behavior than in control patients (p < 0.01). Patients with severe congenital hypothyroidism had the lowest DQ scores compared with two other congenital hypothyroidism subgroups and controls (p < 0.01). Children with congenital hypothyroidism who also had a low level of serum T4 at diagnosis or exhibited a longer thyroid stimulating hormone (TSH) normalization time had lower adaptive behavior scores (p < 0.0003). Bivariate correlation and multiple regression analyses found that the severity of congenital hypothyroidism and parental socioeconomic status correlated with DQ scores. TSH normalization time was negatively related to adaptive behavior scores (p < 0.01). Neurodevelopmental deficits in children with congenital hypothyroidism correlate with the severity of congenital hypothyroidism, TSH normalization time, and parental socioeconomic status.
    Download PDF (496K)
  • Michio Otsuki, Tetsuhiro Kitamura, Kayoko Goya, Hiroshi Saito, Mikio M ...
    2011 Volume 58 Issue 5 Pages 363-367
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: March 25, 2011
    JOURNALS FREE ACCESS
    Urine acidification is induced by metabolic acidosis which is associated with a high intake of protein-rich diet. The purpose of this study was to investigate the relationship of urine acidification with visceral obesity and the metabolic syndrome. We recruited 1,051 male subjects who underwent health examinations at the Health Care Center in Kinki Central Hospital. Subjects who were treated for hypertension, dyslipidemia, diabetes mellitus, and hyperuricemia and had the past history of chronic liver disease, chronic kidney disease and cancer, were excluded in this study. All subjects were administered to urine pH, blood and physical examinations. Lower urine pH was associated with higher serum urea nitrogen which reflects high intake of protein-rich diet, whereas it had no relation to serum creatinine. Lower urine pH was also associated with an increase in waist circumference, homeostasis model assessment-R, fasting plasma glucose, HbA1c, serum triglyceride, serum uric acid and with a decrease in high density lipoprotein cholesterol. Urine pH was not associated with mean blood pressure. Urine acidification is a characteristic of visceral obesity and the metabolic syndrome. High intake of protein-rich diet may contribute urine acidification, which is associated with various metabolic abnormalities in visceral obesity.
    Download PDF (799K)
  • Kazunori Kageyama, Toshihiro Suda
    2011 Volume 58 Issue 5 Pages 369-372
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: March 25, 2011
    JOURNALS FREE ACCESS
    Hyponatremia is known as a complication of neurosurgical conditions or brain. The prevalence of hyponatremia in acute spinal cord injury has been known to be much higher than in the general medical or surgical patient population. We report here a case of hyponatremia, which occurred 10 days after cervical spinal cord injury. The data on sodium levels were improved under the tapered infusion volume and water intake restriction. Treatment for this case is the same as that for syndrome of inappropriate antidiuretic hormone, which have suggested that reduced extracellular volume is important to improve the hyponatremia after traumatic spinal cord injury. Uncontrolled hyponatremia may lead to lethargy, seizures, coma, cardiac arrhythmia and death. Therefore, the complication of hyponatremia should be paid attention after cervical spinal cord injury. A careful monitoring of sodium levels after the injury is required in the cases of cervical spinal cord injury.
    Download PDF (612K)
  • Yasuyuki Kinoshita, Atsushi Tominaga, Kazunori Arita, Kazuhiko Sugiyam ...
    2011 Volume 58 Issue 5 Pages 373-379
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 05, 2011
    JOURNALS FREE ACCESS
    This study is a retrospective analysis of hyponatremia after transsphenoidal surgery in patients with pituitary adenoma. We evaluated (i) the incidence of post-operative hyponatremia (serum Na levels ≤ 135 mEq/L) and the emergence of hyponatremic symptoms, and assessed (ii) the risk factors under a uniform protocol of i.v. infusion with steroid and electrolyte fluid. We examined 88 consecutive operated patients (female: 60; male: 28) with pituitary adenoma. Apart from reconfirming the effects of the purported risk factors, we focused on the degree of serum Na decline on post-operative hyponatremia. Although remained stable during early post-operative period (4 days after surgery), the serum Na levels subsequently decreased after post-operative day 4 in 81 of 88 cases (92.0%). Of 88 patients, 27 (30.7%) and 9 (10.2%) cases suffered from hyponatremia, and developed hyponatremic symptoms. Interestingly, the degree of serum Na levels decline (from pre-operative levels) indicated a useful independent risk factor for monitoring hyponatremic symptoms (p = 0.006) and the degree of decline tended to be greater in elder patients (> 60 years) (p = 0.0346). Serum Na levels should be monitored from, at least, post-operative day 7 to detect early development of hyponatremia. Special attention and recovery effort should be given to elder patients with marked serum Na level decline after surgery.
    Download PDF (560K)
  • Boban Stanojevic, Radan Dzodic, Vladimir Saenko, Zorka Milovanovic, Go ...
    2011 Volume 58 Issue 5 Pages 381-393
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 15, 2011
    JOURNALS FREE ACCESS
    Molecular pathogenesis of papillary thyroid carcinoma (PTC) is largely associated with mutational changes in the BRAF, RAS family and RET genes. Our aim was to assess clinico-pathological and prognostic correlations of these PTC-specific gene alterations, with a particular emphasis on the BRAF mutation, in a group of 266 Serbian PTC patients, for the first time. The reference center-based retrospective cohort included 201 (75.6%) females and 65 (24.4%) males aged 48.0±16.1 years (8-83 years old, range) diagnosed and treated for PTC during 1993-2008. Follow-up period was 53.1±41.6 months (7-187 months, range). BRAF and RAS mutations were determined by direct sequencing of genomic DNA. RET/PTC rearrangements were analyzed by RT-PCR/Southern blotting. Genetic alterations were detected in 150/266 tumors (56.4%). One tumor displayed two genetic alterations. The BRAFV600E was found in 84/266 (31.6%) cases, RAS mutations in 11/266 (4.1%) and RET/PTC in 55/266 (20.7%; 42/266 (15.8%) RET/PTC1 and 13/266 (4.9%) RET/PTC3). On multivariate analysis BRAFV600E was associated with the classical papillary morphology (P = 0.05), the higher pT category (P = 0.05) and advanced clinical stage (P = 0.03). In a proportional hazard model, BRAFV600E did not appear to be an independent risk factor for the faster recurrence (P = 0.784). We conclude that under the extensive thyroid surgery and limited application of radioiodine ablation BRAFV600E may not be an indicator of poorer disease-free survival during the short to middle follow-up period. However, it has a potential to contribute to patients stratification into high- and low-risk groups.
    Download PDF (1092K)
  • Ottó Pintér, Ágnes Domokos, Zsuzsa Mergl, É ...
    2011 Volume 58 Issue 5 Pages 395-407
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 20, 2011
    JOURNALS FREE ACCESS
    Forced swim test (FST) is a widely used test for antidepressant development. Depression is a stress related disease, as hormones of the stress-axis can modify mood. However it is not clear, how the appearance of depressive-like behavior (floating) in FST is connected with changes in the stress-hormone levels. We hypothesized, that different manipulations would alter the behavior through changes in stress-hormone levels. First the effect of environmental alterations was studied. Increasing water-temperature enhanced floating time together with a decrease in adrenocorticotropin levels. During the dark phase of the day rats spent more time with floating independently from the actual lighting. Neither the phase nor the actual lighting had significant effect on adrenocorticotropin concentrations with higher corticosterone levels during the dark phase. At greater water depth rats float less but the size of animals had no effect. Water depth did not influence adrenocorticotropin and corticosterone responses, but the size of the rats significantly affected both factors. Secondly, administration of imipramine reduced floating and adrenocorticotropin level without affecting corticosterone. Despite the known connection between depression and stress we did not find a correlation between floating behavior and hormone levels. As an alternative mechanism imipramine-induced heart rate and core body temperature decrease was found by telemetric approach. This study is the first summary in rats examining the effect of wide range of environmental alterations during FST. It seems likely that both brain monoamines and stress-axis take part in the development of depression, but these pathways are regulated independently.
    Download PDF (1497K)
  • Hyunju Chung, Ho-Yeon Chung, Chong Woo Bae, Chong-Jin Kim, Seungjoon P ...
    2011 Volume 58 Issue 5 Pages 409-420
    Published: 2011
    Released: May 31, 2011
    [Advance publication] Released: April 14, 2011
    JOURNALS FREE ACCESS
    Ghrelin functions as a neuroprotective agent and rescues neurons from various insults. However, the molecular mechanisms underlying ghrelin neuroprotection remains to be elucidated. An accumulation of unfolded proteins in the endoplasmic reticulum (ER) leads to ER stress and then induces ER stress-mediated cell death. Here, we report that acylated ghrelin inhibited tunicamycin- or thapsigargin-triggered ER stress-induced apoptotic cell death in primary rat cortical neurons. An analysis using a specific inhibitor of phosphatidylinositol-3-kinase (PI3K), LY294002, showed that ghrelin prevented apoptosis via the activation of PI3K signaling pathway. Ghrelin suppressed tunicamycin- or thapsigargin-induced upregulation and nuclear translocation of C/EBP homologous protein (CHOP). Ghrelin also inhibited tunicamycin or thapsigargin induction of PRK-like ER kinase (PERK), eukaryotic translation initiation factor-2α (eIF2α) and activating transcription factor (ATF) 4. Exposure of cells to tunicamycin or thapsigargin resulted in nuclear translocation of forkhead box protein O1 (Foxo1), which was reduced by pretreatment with ghrelin. The protective effect of ghrelin was accompanied by an increased phosphorylation of Akt and glycogen synthase kinase (GSK)-3β. Furthermore, ghrelin phosphorylated and inactivated pro-apoptotic BAD and Foxo1. In addition, phospho-Akt was translocated to the nucleus in response to ghrelin and PI3K inhibition by LY294002 prevented ghrelin-induced effect on phospho-Akt localization. Our study suggests that suppression of CHOP activation via the inhibition of PERK/eIF2α/ATF4 pathway and prevention of Foxo1 activation and nuclear translocation may contribute to ghrelin-mediated neuroprotection during ER stress responses. Our data also suggest that PI3K/Akt-mediated inactivation of GSK-3β, BAD and Foxo1 may be associated with the anti-apoptotic effect of ghrelin.
    Download PDF (1869K)
ERRATUM
feedback
Top