The recently identified gastric hormone ghrelin was initially described as a natural Growth Hormone Secretagogue Receptor ligand. Apart from ghrelin's first discovered action, which was the stimulation of Growth Hormone release, implications for many other functions have been reported. It seems that ghrelin exhibits an important role in conditions related to processes regulating nutrition, body composition and growth, as well as heart, liver, thyroid or kidney dysfunction. In this review, current available knowledge about ghrelin's role in various pathological conditions is presented.

View full abstract

It is well-known that estrogens are closely involved in the growth of human breast carcinomas, and that the great majority of breast carcinoma express estrogen receptors. Recent studies have demonstrated that estrogens are locally produced and act on the breast carcinoma tissue. Among these pathways, aromatase is a key enzyme for intratumoral production of estrogens in breast carcinomas, and aromatase inhibitors are currently used in the breast carcinoma in postmenopausal women as an estrogen deprivation therapy. This review summarizes the results of recent studies on the expression and regulation of aromatase in breast carcinoma tissues, and discusses the potential biological and/or clinical significance of aromatase. Aromatase is abundantly expressed in various cell types, such as carcinoma cells, intratumoral stromal cells, and adipocytes adjacent to the carcinoma, in breast carcinoma tissues. Further, a key regulator for aromatase expression differed according to cell type. In addition, aromatase suppressed in situ production of bioactive androgen, 5α-dihydrotestosterone (DHT), in breast carcinoma. Aromatase inhibitors may thus have additional antiproliferative effects through increasing local DHT concentration with estrogen deprivation.

View full abstract

Objective: Hirsutism is one of the component of polycystic ovary syndrome. According to the Rotterdam Consensus has concluded that principially obese women with polycystic ovary syndrome (PCOS) should be evaluated for the metabolic syndrome. The aim of the present study was to investigate the insulin sensitivity in PCOS women with and without hirsutism regardless of obesity. Material and Methods: Clinical characteristics, sex hormones and fasting glucose and insulin levels of fifty-eight women with PCOS were analyzed. Hirsutism has been evaluated through the Ferriman-Gallwey (FG) map scoring system. Results: Twenty-two women (38%) were hirsute. They were not any significant difference between hirsute and nonhirsute women for their sex steroids and insulin sensitivity (P>0.05). There were no correlation among sex steroids, WHR and insulin sensitivity in relation to FG score in the subgroup with hirsutism (P>0.05).Conclusion: Our study suggests that normal weight and overweight women with hirsutism can have normal insulin sensitivity and normal levels of circulating androgens in PCOS women.

View full abstract

Olfactory neuroblastomas are rare, slow-growing malignant tumors, usually diagnosed at advanced stages. Ectopic adrenocorticotropic hormone (ACTH) syndrome caused by an olfactory neuroblastoma is extremely rare. We reported two Korean women who suffered from ectopic ACTH syndrome (EAS) caused by olfactory neuroblastomas. The first patient was a 66-year-old woman who had been diagnosed as olfactory neuroblastoma and refused the management two years before and the second patient was a 37-year-old woman on chemotherapy for olfactory neuroblastoma. In the first case, she presented the Cushingoid appearance with systemic edema and her tumor was removed surgically. ACTH secretion by the tissue was confirmed by immunohistochemistry. By contrast, the second patient presented as severe pneumonia caused by cytomegalovirus and was treated with anti-viral agent followed by chemotherapy and radiotherapy, and her residual mass remained. However, after treatment, both patients' plasma ACTH and cortisol levels returned to normal without any adrenolytic therapy. Considering the causative tumors of EAS can be rarely cured and EAS increases the susceptibility to infections, it is prudent to suppress any hypercortisolemia initially, apart from treating the causal malignancy.

View full abstract

A single nucleotide polymorphism (SNP) located at position-1 in the Kozak sequence of the CD40 gene has been associated with the development of GD in Caucasian and Koreans. This study investigated possible associated between CD40 SNP and the development of GD in a Taiwanese population. To do this, we enrolled 215 Taiwanese patients with GD and 141 controls from the Endocrine Clinic of Kaohsiung Medical University Hospital. This study investigated the association between gene polymorphism and relapse of hyperthyroidism after the discontinuation of medication in three GD patient groups based on time to relapse and a control group, and compared clinical and laboratory data of patients regrouped in three CD40 SNP genotypes. No significant difference in allele or CD40 SNP genotype frequency was observed between patients with GD and control subjects (P = 0.859 and P = 0.959, respectively). Furthermore, we analyzed the distribution of CD40 genotypes and three groups based on time to relapse after drug withdrawal. The cutoff points were 9 months, 9 months to 3 years, and more than 3 yr in subgroups of patients with GD divided by clinical and laboratory variables. Although no significant genotype-phenotype associations were found, the T allele and TT genotype frequency was significantly smaller in GD patients who had developed the disease before 35 years old than those who developed it after 35 years old (x ² = 6.272, P = 0.043) (TT + CT v.s. CC, x ² = 4.951, P = 0.030). These findings suggest that this CD40 gene polymorphism is not associated with GD in Taiwan and is, therefore, not contributing to susceptibility to the disease there.

View full abstract

Oxidative stress and inflammation are known to play roles in the pathogenesis of vascular events. The aim of this study was to investigate the relationship between oxidative stress, inflammation, and atherosclerosis in the general population. A population-based, cross-sectional study was made of 282 people (126 men and 156 women, mean age; 65 13, mean BMI; 25.4 2.7 kg/m ² ) recruited from the Mima study in Tokushima Prefecture. Risk factors included age, sex, body mass index (BMI), cigarette smoking, systolic and diastolic pressure, fasting blood glucose, serum lipids, and high-sensitive C-reactive protein (hs-CRP). Oxidative stress in blood samples was measured by the diacron reactive oxygen metabolites (ROMs) test. The degree of sclerotic change was determined from fundus photographs according to Scheie's classification. After adjustment for age and sex, ROM levels positively correlated with hs-CRP levels, but not with ghrelin, leptin and adiponectin levels. Furthermore, ROM and hs-CRP levels positively and individually correlated with the grade of sclerotic change in the fundus oculi independent of age in a multiple regression analysis. These results suggest that oxidative stress and chronic inflammation promote atherosclerosis in the retinal arteries in the general population.

View full abstract

Objective: Thyroid hormone affects adipocyte function, which in turn influences lipid and carbohydrate metabolism. Adiponectin is one of the adipocytokines that regulates lipid and carbohydrate metabolism. The aim of our study was to evaluate circulating levels of adiponectin in patients with thyroid dysfunction before and after normalization of thyroid function with appropriate medication. Design & Methods: One hundred and twenty patients with hyperthyroidism were recruited at the time of diagnosis. Measurements of free T4 (FT4), thyroid-stimulating hormone (TSH), thyrotropin binding inhibitor immunoglobulin (TBII), adiponectin, fasting blood glucose, fasting serum insulin, lipid profile, and body mass index (BMI) were taken before and after 6 months of medical treatment, at which point all patients were in a euthyroid state. Results: Any change in BMI was strongly correlated with changes in serum-adiponectin levels (r = -0.789, p<0.001). Any change in serum FT4 was also correlated with changes in BMI and serum adiponectin levels (r = -0.254, p = 0.05 and r = 0.501, p = 0.029 respectively). After controlling for BMI changes, we found correlation also between serum FT4 and adiponectin (r = 0.29, p = 0.005). Multivariate-regression analysis still revealed BMI to be a statistically strong predictor for serum-adiponectin level (p<0.001). However, that analysis also revealed thyroid function level as another predictor (p = 0.029). Conclusions: Although BMI is the best predictor of adiponectin, that thyroid hormone might influence circulating levels of adiponectin.

View full abstract

Objectives: Thyroid dysfunction is associated with detrimental cardiovascular effects. We analyzed whether thyroid status is associated with aortic valve sclerosis (AVS) and mitral annular calcification (MAC) as markers of generalized atherosclerosis. Design: Data of 2065 subjects (923 women and 1142 men) aged ≥45 years from the Study of Health in Pomerania (SHIP) were analyzed with respect to low, medium and high TSH levels. Logistic regression models were adjusted for major confounders of atherosclerosis. Main outcome: In women, the prevalence of AVS was the highest in those with low TSH (35.1% vs. 26.7% in medium TSH; p<0.05), while there was a higher prevalence of MAC in men with high TSH levels (9.2% vs. 5.2% in medium TSH; p<0.05). Compared with euthyroid men there was an increased adjusted odds ratio for MAC (OR 2.07; 95% CI 1.12-3.89, p<0.05), for the combination of AVS and MAC (OR 2.13; 95% CI 1.08-4.21, p<0.05) or for one of both (OR 1.47; 95% CI 1.02-2.13, p<0.05) among men with high TSH. No such association was found in women. Conclusions: There was an association between thyroid function and valvular sclerosis. Men with high TSH values had increased odds for AVS or MAC, and the combination of both. These findings may reflect an increased atherosclerotic state in affected subjects.

View full abstract

To determine the impact of blood glucose profile, involving fluctuation and excursion of blood glucose levels, on glycated proteins, we evaluated the association among the daily profile of blood glucose, and glycated albumin (GA) and HbA1c levels in patients with type 1 diabetes (n = 93) and type 2 diabetes (n = 75). GA levels were strongly correlated with HbA1c levels in type 1 (r = 0.85, P<0.0001) and type 2 diabetes (r = 0.61, P<0.0001), respectively. HbA1c levels were similar between patients with type 1 and type 2 diabetes, while GA levels were significantly higher in type 1 diabetes. Thus the ratio of GA levels to HbA1c levels was significantly higher in type 1 diabetes than that in type 2 diabetes (3.32 0.36 vs. 2.89 0.44, p<0.001). The degrees of GA levels and HbA1c levels correlated with maximum and mean blood glucose levels in patients with type 1 and type 2 diabetes. Stepwise multivariate analysis revealed that GA levels independently correlated with maximum blood glucose levels in type 1 diabetes (F = 43.34, P<0.001) and type 2 diabetes (F = 41.57, P<0.001). HbA1c levels also independently correlated with maximum blood glucose levels in type 1 diabetes (F = 34.78, P<0.001), as well as being correlated with mean blood glucose levels in type 2 diabetes (F = 11.28, P<0.001). In summary, GA could be a better marker for glycemic control than glycated hemoglobin in diabetic patients, especially for evaluating glycemic excursion, which is considered to be a major cause of diabetic angiopathy.

View full abstract

Mitochondrial diabetes is characterized by diabetes and hearing loss in maternal transmission with a heteroplasmic A3243G mutation in the mitochondrial gene. In patients with the mutation, it has been reported that hepatic involvement is rarely observed. We demonstrated a case of hypertrophic cardiomyopathy and hepatic failure with mitochondrial diabetes. To clarify the pathogenesis we analyzed the mitochondrial ultrastructure in the myocytes, the reactive oxygen species (ROS) production in the liver and the status of heteroplasmy of the mitochondrial A3243G mutation in the organs involved. In cardiomyocytes and skeletal muscle, electron microscopic analysis demonstrated typical morphological mitochondrial abnormalities. Immunohistochemical analysis demonstrated enhanced ROS production associated with marked steatosis in the liver, which is often associated with mitochondrial dysfunction. Analysis of the A3243G mutation revealed a substantial ratio of heteroplasmy in these organs including the liver. The presence of steatosis and enhanced oxidative stress in the liver suggested that hepatic failure was associated with mitochondrial dysfunction.

View full abstract

Adiponectin has been proposed to act as an antidiabetic adipokine, suppressing gluconeogenesis and stimulating fatty acid oxidation in the liver and skeletal muscle. Although adiponectin-knockout (adipo(-/-)) mice are known to exhibit insulin resistance, the degrees of insulin resistance and glucose intolerance are unexpectedly only moderate. In this study, the adipo(-/-) mice showed hepatic, but not muscle, insulin resistance. insulin-stimulated phosphorylation of IRS-1 and IRS-2 was impaired, the IRS-2 protein level was decreased, and insulin-stimulated phosphorylation of Akt was decreased in the liver of the adipo(-/-) mice. However, the triglyceride content in the liver was not increased in these mice, despite the decrease in the PPARalpha expression involved in lipid combustion, since the expressions of lipogenic genes such as SREBP-1 and SCD-1 were decreased in association with the increased leptin sensitivity. Consistent with this, the down-regulation SREBP-1 and SCD-1 observed in the adipo(-/-) mice was no longer observed, and the hepatic triglyceride content was significantly increased in the adiponectin leptin double-knockout (adipo(-/-)ob/ob) mice. On the other hand, the triglyceride content in the skeletal muscle was significantly decreased in the adipo(-/-) mice, probably due to up-regulated AMPK activity associated with the increased leptin sensitivity. In fact, these phenotypes in the skeletal muscle of these mice were no longer observed in the adipo(-/-)ob/ob mice. In conclusion, adipo(-/-) mice showed impaired insulin signaling in the liver to cause hepatic insulin resistance, however, no increase in the triglyceride content was observed in either the liver or the skeletal muscle, presumably on account of the increased leptin sensitivity.

View full abstract

To evaluate the relationship between the adiponectin levels and left ventricular mass index (LVMI) in uncomplicated obese subjects. Fifty-nine subjects were assigned to the obese (BMI≥30 kg/m ² ) and 58 to the lean (BMI<30 kg/m ² ) group. Plasma glucose, insulin, serum total cholesterol and high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, triglycerides and adiponectin were measured. Insulin resistance was determined by the Homeostasis Assessment Model (HOMA-IR). The left ventricular functions of all subjects were determined by 2D and pulse wave Doppler echocardiography. LVMI was calculated as left ventricular mass (LVM) normalized for height in m ^2.7 . The obese group displayed significantly higher LVMI and late mitral inflow velocity. Thirty-three obese subjects met the criteria for left ventricular hypertrophy (LVH) and had lower serum adiponectin levels compared with obese subjects without LVH and lean subjects (p<0.05). Adiponectin was negatively correlated with LVMI (R: -0.277, p: 0.002). Furthermore, during the partial correlation analysis where HOMA-IR was controlled, the negative correlation between adiponectin and LVMI progressed (r: -0.283, p: 0.002). The linear regression analysis showed an independent relationship between LVMI and adiponectin. (β: -0.214, p: 0.01) Obesity is associated with LVH. This study showed direct influence of adiponectin on LVMI.

View full abstract

Hachimi-jio-gan is widely used to improve several disorders associated with diabetes, but its mechanism remains poorly understood. In an attempt to clarify the mechanism of Hachimi-jio-gan, we investigated the effects of this herbal medicine and its components in transfection studies of CV1 cells, especially nuclear receptor-mediated actions. One half (0.5) mg/ml of Hachimi-jio-gan activated peroxisome proliferator-activated receptor (PPARα), mediating the activation by 3.1-fold on DR1 response elements; however, it did not affect PPARγ, thyroid hormone receptor, androgen receptor, estrogen receptor or RXR. In addition, this activation was observed in a dose-dependent manner. Next, to determine which components of Hachimi-jio-gan activate PPARα-mediated transcription, 8 of its components (rehmanniae radix, orni fructus, dioscoreae rhizoma, alismatis rhizoma, hoelen, moutan cortex, cinnamomi cortex, aconiti) were tested. Only cinnamomi cortex (1.0 mg/ml) increased PPARα-mediated transcription by 4.1-fold, and this activation was specific for PPAR α, and not for other nuclear receptors. Moreover, this PPARα-related activation by cinnamomi cortex is specifically observed in renal cells. Taken together, these findings indicate that Hachimi-jio-gan and cinnamomi cortex may have a pharmacological effect through the target site for PPARα.

View full abstract

The present study was conducted to establish a method to induce differentiation of bone marrow (MB)-derived mesenchymal cells into insulin-producing cells. When mouse BM-derived mesenchymal cells were cultured for 60 days in medium containing 10% fetal calf serum and 25 mM glucose, they expressed insulin. Addition of activin A and betacellulin (BTC) accelerated differentiation, and immunoreactive insulin was detected 14 days after the treatment. Insulin-containing secretory granules were observed in differentiated cells by electron microscopy. Treatment of BM-derived mesenchymal cells with conophylline (CnP) and BTC-delta4 further accelerated differentiation, and mRNA for insulin was detected 5 to 7 days after the treatment. Mesencymal cells treated with CnP and BTC-delta4 responded to a high concentration of glucose and secreted mature insulin. When these cells were transplanted into streptozotocin-treated mice, they markedly reduced the plasma glucose concentration, and the effect continued for at least 4 weeks. These results indicate an efficacy of the combination of CnP and BTC-delta4 in inducing differentiation of BM-derived mesenchymal cells into insulin-producing cells.

View full abstract

This report documents a case with primary amenorrhea associated with sensorineural hearing loss and anosmia. The patient presented at 18 years of age with minimal sexual development and no prior menses. Her mother also presented late onset menarche, hearing loss and anosmia, and her father was also affected with hearing loss. A chromosome analysis of the patient showed 46, XX. Basal FSH and LH levels were in normal range, but the serum estradiol level was low. A serum estradiol elevation and follicular development were recognized after the injection of human menopausal gonadotropin. Genomic DNA sequencing of FSHB, FSHR, KAL1, FGFR1, PROK2 and PROKR2 did not show any mutation. Audiometry showed severe bilateral sensorineural hearing loss and smell testing confirmed a severely impaired olfactory function. These findings probably suggested a case of delayed puberty associated with sensorineural hearing loss and anosmia.

View full abstract

Adiponectin is an anti-diabetic and anti-atherogenic adipokine that serves as a major determinant of insulin sensitivity. Thiazolidine derivatives increase circulating adiponectin, particularly the high molecular weight isoform, which has been shown to well correlate with amelioration of insulin resistance by thiazolidines in diabetic patients. α-glucosidase inhibitors are another class of anti-diabetic agents that specifically reduce postprandial blood glucose elevations, but its effect on adiponectin is largely unknown. In the present study we investigated effect of an α-glucosidase inhibitor, acarbose, together with pioglitazone, the only thiazolidine derivative available in Japan, on serum concentrations of adiponectin. Seventeen patients with type 2 diabetes were treated with acarbose and sixteen with pioglitazone for three months. Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49% and 0.63%, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin. In conclusion, acarbose increases serum concentrations of total adiponectin without preference of the high molecular weight isoform in type 2 diabetic patients. Clinical relevance of the increased adiponectin to the acarbose effects remains to be elucidated.

View full abstract

We here report a novel mutation of the thiazide-sensitive Na-Cl cotransporter (TSC) (SLC12A3) gene in a Japanese patient with Gitelman's syndrome (GS). GS is characterized by a renal disorder and is associated with hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria arising from the defective tubular reabsorption of magnesium and potassium. This disease is reportedly caused by mutations in the TSC gene. A 52-year-old man was referred to our hospital because of sleeplessness and tinnitus. He exhibited hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic hyperaldosteronism. A renal clearance study revealed that the administration of furosemide decreased chloride reabsorption; however, the ingestion of thiazide failed to decrease chloride reabsorption. A diagnosis of GS was made based on the clinical features, laboratory data and renal function test results. Sequencing of the patient's genomic DNA revealed an A to T transition at the initial codon of exon 1 of the TSC gene (c1A>T). Knowledge of this novel mutation may be helpful for understanding the pathophysiology of GS and the function of TSC as well as for providing genetic counseling.

View full abstract

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers. A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.

View full abstract

Leptin, one of adipocytokines, plays a wide range of important roles in reproductive biology. We have previously reported that low hypo-adiponectinemia might be involved in the pathophysiology of overweight preeclampsia (PE) patients. Moreover, recent reports have underscored the importance of circulating angiogenic factors in the pathophysiology of PE. Here, we examined whether leptin in conjunction with adiponectin and/or angiogenic factors plays some role in the pathophysiology of PE. We performed a cross-sectional study in 34 PE patients and normal pregnancies matched for gestational age and body mass index as controls. We measured serum concentrations of leptin, adiponectin, the angiogenic factors vascular endothelial growth factor (VEGF), placental growth factor, and the soluble VEGF receptors sFlt-1 and sFlk-1. We observed that leptin levels in PE patients were significantly higher compared with those in controls, but did not observe significant differences between normal- and overweight patients in both groups. We also showed a significant negative correlation between leptin and adiponectin in controls, but not in PE patients. There was a significant correlation between leptin and sFlt-1 in PE patients, while there were significant differences of body mass index, mean blood pressure and proteinuria between high and low leptin/sFlt-1 ratio group in PE patients. Moreover, there was a significant difference of leptin level between IUGR and normal growth group in PE patients. These results suggest that the circulating increased leptin might be derived mainly from the placenta and regulated by the placental hypoxic condition, whereas adiponectin might be derived mainly from adipose tissue; and that leptin might play some role through insulin resistance, autonomic activation, or direct effect on endothelium with other angiogenic factors in pathophysiology of PE compared with the exaggerated release of adiponectin from adipose tissue.

View full abstract

Cholesterol sulfate (CS) is a component of cell membranes that plays a role in stabilizing the cell membrane. We previously reported that CS increased in the endometrium during implantation, suggesting that CS plays an important role in reproduction. It has been reported that CS regulates progesterone and pregnenolone production in the placenta, adrenal glands and ovary. The regulatory mechanisms of steroid hormone production by CS, however, are still unknown. In the present study, we investigated the effect of CS on the expression of progesterone production-related genes in KGN cells, derived from human granulosa-like tumor. KGN cells were cultured with CS (10 μM) or cholesterol (10 μM) in the presence of 8-bromo-cAMP (1 mM). Progesterone levels in the culture media were measured by enzyme linked fluorescent assay at 24 h after treatment of CS and cAMP. Total RNAs were extracted for quantitative real time RT-PCR with specific primer of StAR protein, P450scc, HSD3B2, ferredoxin and ferredoxin reductase. Whole cell lysates were extracted for western blot analysis with antibody for StAR protein. Progesterone concentration in the culture medium increased to 38-fold by treatment of cAMP. CS significantly reduced progesterone concentration by 30% compared with those of cAMP treatment (p<0.05), while cholesterol did not change the progesterone concentration. CS treatment down-regulated the expression of StAR mRNA and P450scc mRNA was to 54% and 60%, respectively (p<0.05). Western blot analysis revealed that the amount of StAR protein was also reduced by CS treatment. The expression of HSD3B2 mRNA was up-regulated to 3.4-fold by treatment of cAMP. The expression of ferredoxin and ferredoxin reductase mRNA was not affected by CS treatment. These data implied that CS has an inhibitory effect on progesterone production by regulating the expression of StAR and P450scc gene expression.

View full abstract

We aimed to determine whether ultrasonography is a useful diagnostic tool by correlating its findings with biological data of patients with subacute thyroiditis (SAT). Thirty-two SAT patients were evaluated in a retrospective study. Thirty-one patients (96.9%) had tenderness, 14 (43.8%) had localized pain, and 11 patients (34.4%) had radiating pain during a state of SAT. With ultrasonography, we found 51 hypoechoic areas in 32 patients. The hypoechoic volume per unilateral thyroid gland (%) was significantly larger in areas accompanied with pain (P<0.001). Out of 27 patients measured, 18 (67%) were positive for thyroglobulin antibodies (TgAb), of whom all were females. TgAb levels ranged from 0.3 to 13.8 U/ml. During therapy, TgAb levels gradually increased in 2 of the 7 patients who were measured several times. Both thyroglobulin antigen (TgAg) and free thyroxine (FT4) correlated well with total hypoechoic volume (cm ³ ), and the TgAg level showed a strong correlation with the FT4 level (r = 0.7; P<0.0001). The area (%) that the hypoechoic volume occupied in the total thyroid gland, even if the area was over half, was not related to the need of L-T4 replacement therapy. Also, none of the other variables (age, days from onset until diagnosis, serum levels of FT4, TgAg, CRP, autoantibodies, therapies, treatment) differed between the patients with and without replacement therapy. In summary, we found that the hypoechoic area in patients with SAT reflected the degree of inflammation and thyroid hormone levels, though it was difficult to predict continuous hypothyroidism.

View full abstract

A 77-year-old man was diagnosed as having hypothyroidism. An electrocardiogram obtained at the time of the first examination revealed Brugada electrocardiographic waveforms in leads V1 to V3. When pilsicainide hydrochloride loading changed the waveforms of the electrocardiographic ST segment, this result suggested an abnormality of the cardiac muscle sodium channels. The Brugada electrocardiographic waveforms disappeared with the normalization of thyroid function. This case is the first report ever of hypothyroidism that presented Brugada electrocardiographic waveforms. The results obtained in this case suggested that thyroid functions changed the waveforms of the electrocardiogram because of its effect on myocardial ion channels.

View full abstract

The use of octreotide-LAR and cabergoline therapy has shown great promise in adults with acromegaly; however, the experience in pediatric patients has rarely been reported. We described a clinical course of a 15-year-old boy of McCune-Albright syndrome (MAS) with pituitary gigantism. At the age of 8 years, a growth hormone (GH) and prolactin (PRL) producing pituitary adenoma was diagnosed at our hospital. He also had multiple fibrous dysplasia, so that he was diagnosed as having MAS. The tumor was partially resected, and GNAS1 gene mutation (R201C) was identified in affected tissues. We introduced octreotide to suppress GH secretion (100 μg 2/day s.c). During therapy with octreotide, IGF-1 and GH levels could not be suppressed and the patient frequently complained of nausea from octreotide treatment. Therefore, the therapy was changed to monthly injections of octreotide-LAR at the age of 12.3 years and was partially effective. However, as defect of left visual field worsened due to progressive left optic canal stenosis, he underwent second neurological decompression of the left optic nerve at 13.4 years of age. After surgery, in addition to octreotide-LAR, cabergoline (0.25 mg twice a month) was started. This regimen normalized serum levels of GH and IGF-1; however, he showed impaired glucose tolerance and gallstones at 15.7 years of age. Therefore, the dose of octreotide-LAR was reduced to 10 mg and the dose of cabergoline increased. This case demonstrated the difficulty of treating pituitary gigantism due to MAS. The use of octreotide-LAR and cabergoline should be considered even in pediatric patients; however, adverse events due to octreotide-LAR must be carefully examined.

View full abstract

Excessive iodine exposure was reported to be associated with thyroid dysfunctions.The aim of this study is to evaluate the link between excess urinary iodine as the prime indicator of excessive iodine intake and autoimmune subclinical hypothyroidism (SCH) among Egyptian women. Seventy three women with autoimmune SCH and 60 age- matched healthy women as controls were enrolled in this study. TSH, FT4, urinary iodine concentrations (UIC) and thyroid peroxidase antibody (TPOAb) were estimated. The levels of urinary iodine were significantly higher in patients with SCH as compared with control subjects, (326.97 112.98 vs. 274.45 98.75 ug/l, p<0.01). In patients with SCH, there was a significant correlation between UIC and TSH levels. Also, a significant correlation between UIC and TPOAb was found. We conclude that excessive iodine intake may trigger thyroid autoimmunity and eventually thyroid hypofunction among Egyptian women.

View full abstract

An insulinoma is characterized by endogenous hyperinsulinemia and hypoglycemia. However, it has been reported that insulinomas with normal levels of plasma insulin and a normal insulin to glucose ratio occur in patients with hypoglycemia. Although overproduction of Insulin-like growth factor II (IGF-II) by non-islet cell tumors such as large mesenchymal tumors, can cause hypoglycemia, no cases of circulating plasma IGF-II from an islet cell tumor contributing to hypoglycemia have been reported. We report here a rare case of a pancreatic islet tumor in a patient with hypoglycemia that was associated with increased plasma IGF-II, which returned to normal after tumor resection.

View full abstract

Introduction: Teriparatide (recombinant human PTH 1-34/TPTD) is an osteoanabolic agent available for osteoporosis treatment. The aim of this prospective trial was to evaluate the acute and chronic effects of TPTD in endogenous intact PTH (iPTH) levels in postmenopausal women with established osteoporosis. Materials and methods: Thirty-six postmenopausal Caucasian women (age 66.6 1.4 years) with established osteoporosis received TPTD 20 μg once daily for eighteen months. Follow-up was continued for another six months after treatment discontinuation for a total of 24 months. Serum calcium, phosphate, total alkaline phosphatase (ALP) and iPTH were obtained from all women before and one hour, one day, as well as one, six, twelve, 18 and 24 months after treatment initiation. Lumbar spine bone mineral density was measured before, as well as twelve and eighteen months after treatment initiation. Results: iPTH levels decreased from the first hour of treatment, remained suppressed as long as TPTD was administered and increased after treatment discontinuation (p<0.001). Total ALP followed an opposite pattern. Serum calcium remained within normal range. Conclusions: iPTH levels are suppressed rapidly and persistently during TPTD administration whereas they return to baseline after treatment discontinuation; therefore, they can serve as an index of patient's compliance to treatment.

View full abstract