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Biomedical subjects

Kazue Takano

Publications and source records attributed to Kazue Takano.

At least 19 recordsLinked to original sources
PubMed2006

Expression of type 5 somatostatin receptor in TSH-secreting pituitary adenomas: a possible marker for predicting long-term response to octreotide therapy.

In TSH-secreting pituitary adenomas (TSHoma), octreotide (OCT) therapy reduces tumor size and TSH secretion in some cases but not in others. As OCT acts through various types of somatostatin receptors (SSTRs), the different responses of TSHoma to OCT might be explained by the differences of SSTR expression. We therefore studied the expression of subtype-specific SSTR mRNA transcripts in tumor tissues by RT-PCR. Type 2 (SSTR2) mRNA transcripts were detected in all 8 tumors but those of SSTR3 and SSTR5 were demonstrated only in 5 of them. Serum TSH levels were decreased by OCT administration test in all patients but OCT therapy was effective in two patients out of three. SSTR5 mRNA was detected in two tumors from the responder, but not in one tumor that was resistant to OCT. These observations suggest that the temporal decrease of TSH by OCT may be mediated by SSTR2, and that the long term response to OCT therapy may be related with the expression of SSTR5. Therefore, the expression of SSTR5 in TSHoma may be a useful marker for predicting the outcome of the therapy, but further studies with larger numbers of patients are necessary.

Adenoma↗
PubMed2006

Growth hormone (GH) effects on central fat accumulation in adult Japanese GH deficient patients: 6-month fixed-dose effects persist during second 6-month individualized-dose phase.

Both Japanese and Caucasian adults with GH deficiency (GHD) have pronounced abdominal obesity, which is associated with increased risk of cardiovascular complications. We investigated the effects of GH treatment in 27 adult Japanese GHD patients, 15 with adult onset (AO) and 12 with childhood onset (CO) GHD. Patients initially received GH titrated to 0.012 mg/kg/day for 24 weeks in a double-blind design and the dose was then individualized for each patient according to IGF-I for a further 24 weeks. Dual-energy x-ray absorptiometry (DXA) data were evaluated for percentages of trunk fat, total body fat and lean body mass. Serum IGF-I and lipid concentrations were determined at a central laboratory. There were 25 patients who completed 48 weeks of treatment, with 7, 6 and 12 patients then receiving GH at 0.003, 0.006 and 0.012 mg/kg/day, respectively. With the reductions in dose when individualized between weeks 24 and 48, mean serum IGF-I level was reduced and excessively high values, observed in AO patients on the fixed GH dose, were no longer seen. The decrease from baseline in trunk fat was similar at week 24 (-3.8 +/- 3.3%, p<0.001) and week 48 (-3.1 +/- 3.7%, p<0.001), and the difference between changes was not significant. Total cholesterol was decreased from baseline by -24 +/- 28 mg/dl (p<0.001) at week 24 and -17 +/- 28 mg/dl (p = 0.007) at week 48. Two patients had elevated HbA1c levels: one continued GH treatment after a dose reduction and the other discontinued due to persistent impaired glucose tolerance. Therefore, excessively high IGF-I levels can be avoided by individualized dosing during long-term GH treatment. Individualized dosing maintains the decrease in abdominal fat in adult Japanese GHD patients and should reduce the cardiovascular risk.

Abdominal Fat↗
PubMed2006

Low-dose growth hormone treatment (0.175 mg/kg/week) for short stature in patients with Turner Syndrome: data from KIGS Japan.

Turner syndrome is a common sex chromosome anomaly. Human growth hormone (hGH) is effective for treating short stature, which is a major characteristic of the disease. In this report, we analyzed the results of low-dose GH treatment for short stature in 212 Turner syndrome patients with growth hormone deficiency. These patients were enrolled in KIGS Japan. After 5 years of treatment, change in height was more than the mean growth curve in many patients, and the standard deviation (SD) for stature improved by +1.22 SDS. As the treatment progressed, the weight-for-height index (WHI) decreased in patients aged 8.1 years or older but not more than 14.8 years at the commencement of the treatment.

Adolescent↗
PubMed2006

Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia.

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62+/-1.8, range; 9-86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 microU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4+/-0.6 kg/m2) and serum total protein levels (6.6+/-0.1g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.

Adolescent↗
PubMed2006

Hyponatremia after transsphenoidal surgery for hypothalamo-pituitary tumors.

Transient diabetes insipidus is a well-known complication after transsphenoidal surgery (TSS). On the other hand, transient hyponatremia has been reported as being a delayed complication of TSS. Transient hyponatremia has been attributed to the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), but the details of hyponatremia have not been clarified. In the present study, we retrospectively reviewed 110 consecutive patients (39 males and 71 females, age 9-80 years) operated on transsphenoidally for pituitary and hypothalamic tumors. We investigated the frequency, time of onset, duration of hyponatremia after TSS, and analyzed possible factors associated with it. A postoperative sodium concentration <135 mEq/l was observed in 29 (26%) patients. Five patients were excluded from this study because their hyponatremia could be due to either overdose of desmopressin or SIADH for meningitis. Therefore, we investigated 24 (22%) patients with hyponatremia in this study. The sodium levels in the patients with hyponatremia ranged from 110 to 134, with a mean of 126.2 +/- 5.3 mEq/l. Hyponatremia was observed on average on postoperative day 9.5 +/- 2.4, the serum sodium levels normalized within 3.8 +/- 1.7 days. Hyponatremia occurred in patients with non-functioning pituitary adenoma (26%, 11/42), Rathke's cleft cyst (29%, 5/17), prolactinoma (31%, 4/13) and acromegaly (15%, 4/27). 18 patients (75%, 6/24) who developed hyponatremia had macrotumor (>10 mm), and 6 patients (25%, 6/24) had microtumor. The plasma arginine vasopressin (AVP) levels in the patients with hyponatremia ranged from 0.21 to 2.1, with a mean of 0.79 +/- 0.46 pg/ml, and the levels were inversely correlated with plasma osmolality (r = -0.80, p = 0.002). The urine to plasma osmolality ratios were >1. All the patients received appropriate hormonal replacement, including hydrocortisone. These data showed that postoperative hyponatremia after TSS was not rare, and the hyponatremia was mainly associated with SIADH. As the hyponatremia could be a life-threatening complication, all patients should be screened for serum electrolytes after TSS.

Adolescent↗
PubMed2006

Metabolic disorders in adult growth hormone deficiency: A study of 110 patients at a single institute in Japan.

The purpose of this study carried out at a single institute in Japan was to investigate the clinical characteristics and complications of patients with adult growth hormone deficiency (GHD). Clinical and biochemical data of 110 patients (50 males, 60 females; mean age 42 +/- 17 yr) with adult GHD who attended Tokyo Women's Medical University between 1990 and 1999 were analyzed retrospectively from medical records. This retrospective analysis demonstrated that 109 patients had multiple pituitary hormone deficiencies, with 98 patients having a deficiency of more than three hormones. Sixty-one patients had childhood onset GHD (COGHD) while the remaining 49 patients had adulthood onset GHD (AOGHD). Body mass index (BMI) ranged from 16.9 to 35.9 with a mean of 23.9 +/- 4.1 (kg/m2), with BMI being > or = 25 kg/m2 in 38 patients (31% of COGHD and 38% of AOGHD). Forty-one percent of the patients had hypercholesterolemia, 41% had hypertriglyceridemia, 47% had decreased levels of HDL cholesterol and 48% had increased levels of LDL cholesterol. Intima-media thickness (IMT) of the carotid arteries was investigated in 33 patients, with abnormal findings including increased IMT or plaque being observed in 4 of 18 COGHD patients and 4 of 15 AOGHD patients. Diabetes mellitus and impaired glucose tolerance was found in 4 COGHD patients and 16 AOGHD patients. Insulin resistance was assessed in 36 patients by the homeostasis model insulin resistance index (HOMA-R) and ranged from 0.65 to 10.58 with a mean of 2.80 +/- 0.37. This mean value of HOMA-R was significantly greater than that measured in normal subjects (1.58 +/- 0.05: P < 0.05). These data suggest that abnormal lipid and glucose metabolism, and atherosclerotic changes occur frequently in adult patients with GHD. Insulin resistance may play a role in glucose and lipid metabolism disorders associated with GHD.

Adolescent↗
PubMed2006

Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years.

Although there are two types of amiodarone-induced thyrotoxicosis (AIT), only type II AIT has been seen at our institution in Japan so far. There have been few case reports of AIT recurrence, probably because of the fact that amiodarone is immediately discontinued once AIT has developed. Our own policy is not to discontinue amiodarone in all AIT patients, unless severe adverse effects such as pulmonary fibrosis develop. Among more than 50 patients with type II AIT we have encountered, three with arrhythmogenic right ventricular cardiomyopathy showed AIT recurrence. In these patients, the first episode of AIT developed 3, 4, and 2 years after the start of amiodarone administration, and recurrence was observed 5, 6, and 8 years after the first episode, respectively. The AIT resolved spontaneously in all cases while the patients continued to take amiodarone. In comparison with the first AIT episode, the second was milder and resolved within a shorter period. These three cases suggest that recurrence of type II AIT may not be rare in iodine-sufficient areas, and that it is relatively mild and may resolve spontaneously. Furthermore, at least in Japan, it may be possible for patients with recurrent type II AIT to continue taking amiodarone.

Aged↗
PubMed2006

Etiology of hypercholesterolemia in patients with anorexia nervosa.

OBJECTIVE: Hypercholesterolemia is common in patients with anorexia nervosa (AN) despite emaciation. The objective of this study was to clarify the mechanism of hypercholesterolemia in AN. METHOD: We measured serum lipids in 39 patients with AN and analyzed serum lipid profiles in the 24 patients in comparison with five age-matched controls. RESULTS: Mean serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ketone bodies, apolipoprotein (apo)-A1, B, C2, C3, E, and cholesterol ester transfer protein (CETP) activity were significantly higher in patients with AN than in controls. No significant difference in serum free fatty acid (FFA) levels was observed between patients with AN and controls. CETP was accelerated in patients with AN with hypercholesterolemia. No correlation was apparent between serum levels of cholesterol and thyroid hormones. CONCLUSION: Serum levels of cholesterol, CETP, and apolipoproteins decreased after weight gain, indicating that cholesterol metabolism is accelerated in patients with AN with normal serum levels of FFA.

Adolescent↗
PubMed2006

Iodide inhibits vascular endothelial growth factor-A expression in cultured human thyroid follicles: a microarray search for effects of thyrotropin and iodide on angiogenesis factors.

OBJECTIVE: Excess iodide has been administered to hyperthyroid patients before thyroid surgery to reduce intraoperative bleeding and oozing. The purpose of this study was to elucidate the mechanism by which iodide reduces blood flow in the hypervascular thyroid gland. DESIGN: Human thyroid follicles were cultured in the presence or absence of thyrotropin (TSH), or in medium containing various concentrations of iodide, and TSH-or iodide-regulated gene expression was analyzed by cDNA microarray. MAIN OUTCOME: TSH stimulated the expression of thyroglobulin, peroxidase, sodium iodide symporter, vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor (PGF) but decreased that of VEGF-C by half. When thyroid follicles were cultured in high-iodide (10(5) M) medium, TSH-induced expression of VEGF-A, VEGF-B, and PGF was decreased, accompanied by a reduction of VEGF-A release into the medium. Furthermore, expression of putative angiogenesis inhibitors such as urokinase-type plasminogen activator (PLAU) was increased. These findings were confirmed by real-time polymerase chain reaction (PCR) and Northern blot hybridization. CONCLUSIONS: We have demonstrated for the first time that iodide at high concentration decreases the expression of the angiogenic factors VEGF-A, VEGF-B, and PGF, accompanied by an increase in the expression of possible antiangiogenic factors such as PLAU. These proangiogenic and antiangiogenic factors may at least partly account for the iodide-induced decrease in thyroid blood flow.

Blotting, Northern↗
PubMed2006

Effect of growth hormone treatment on trunk fat accumulation in adult GH-deficient Japanese patients: a randomised, placebo-controlled trial.

OBJECTIVE: Patients with growth hormone deficiency (GHD), both Japanese and Caucasian, have an abnormal body composition with pronounced abdominal obesity. This study aimed to evaluate changes in trunk fat with GH treatment. DESIGN: Double-blind, placebo-controlled study. PATIENTS AND MEASUREMENTS: Sixty-one Japanese adult GH deficient patients (mean age 37 years) were randomised to either GH, titrated to 0.012 mg/kg/day, (n = 30) or placebo (n = 31) for 24 weeks. Body composition, by dual-energy X-ray absorptiometry (DXA), was evaluated at a central laboratory for trunk fat, total body fat and lean body mass. Serum lipid levels were also determined centrally. RESULTS: At baseline, 26 (42.6%) patients had a body mass index (BMI) > or = 25 kg/m(2), the threshold for obesity-related complications for Japanese subjects. Median trunk fat mass (FM) was > or = 9.0 kg for each treatment and gender group, higher than the cut-off for increased age-adjusted risk for cardiovascular complications reported in the normal Japanese population. After 24 weeks of GH treatment, the change in percentage trunk FM was -3.4 +/- 0.6%, versus 0.4 +/- 0.6% with placebo (p < 0.001). Change in total body FM was -2.8 +/- 0.5% with GH and 0.0 +/- 0.5% with placebo, indicating that the decrease in trunk fat was more pronounced than for total body fat. Total and low density lipoprotein (LDL)-cholesterol were both significantly (p < 0.001) decreased compared with placebo. One patient discontinued due to a subdural haematoma and one had GH dose reduced due to hyperglycaemia. CONCLUSIONS: Japanese patients with GHD have abnormal central fat accumulation, which is reduced by GH treatment over 24 weeks. This may reduce cardiovascular risk but the GH dose should be individualised to maintain IGF-I in the normal range.

Abdominal Fat↗
PubMed2006

Transcatheter arterial embolization for the treatment of liver metastases in a patient with malignant pheochromocytoma.

A 63-year-old male patient was admitted for the treatment of malignant pheochromocytoma with multiple liver metastases. Plasma and urinary levels of catecholamines were elevated. Transcatheter arterial embolization (TAE) with concomitant administration of mitomycin C and gelatin sponge was performed for the treatment of liver metastases. Dose of alpha-1 blocker before TAE was increased to prevent hypertensive crisis during and after TAE. The hepatic metastatic lesion of CT findings was decreased after TAE. Although blood pressure showed a transient hypertension (180/100 mmHg) after every TAE, it returned rapidly to normal. The patient experienced transient abdominal pain, nausea, and loss of appetite after every TAE; however, those symptoms were readily controlled by conventional medications. Slight elevation of liver transaminases was recognized but returned to normal range within 3 weeks. No other major side effects were seen with TAE. While plasma and urinary level of catecholamines were unchanged, plasma chromogranin A (CgA) level was significantly decreased. These results suggest that TAE is a useful treatment for hepatic metastases. Plasma CgA level is a useful marker in the treatment of malignant pheochromocytoma.

Adrenal Gland Neoplasms↗
PubMed2005

Pediatric nonalcoholic steatohepatitis associated with hypopituitarism.

We experienced two cases of pediatric nonalcoholic steatohepatitis (NASH) associated with hypopituitarism. The first patient was diagnosed with a craniopharyngioma at 5 years of age. After an operation to treat the condition, the patient gradually became obese, and an elevation of transaminases was observed. At 16 years of age, the patient was diagnosed as having NASH with liver cirrhosis. He was started on hormone replacement therapy; however, his insulin resistance and liver fibrosis, as evaluated by hyaluronic acid and platelet count, progressed. In addition, his hyperleptinemia continued. The second patient was diagnosed, at 10 years of age, as having pituitary dysfunction due to fetal asphyxia, and he was started on hormone replacement therapy. This patient was noted to have been obese throughout his life. He was diagnosed as having NASH with advanced fibrosis at 18 years of age. It is important for both hepatologists and endocrinologists to be aware of the association between pituitary dysfunction and NASH.

Adiponectin↗
PubMed2005

Diagnosis of thyroid follicular carcinoma by the vascular pattern and velocimetric parameters using high resolution pulsed and power Doppler ultrasonography.

The aim of this study was to define the preoperative diagnosis of thyroid follicular carcinoma by the vascular pattern and velocimetric parameters using high resolution pulsed and power Doppler ultrasonography (US). We compared the vascular pattern and the velocimetric parameters, such as peak systolic velocity (Vmax), end-diastolic velocity (Vmin), pulsatility index (PI), or resistance index (RI) between follicular adenoma (FA, n = 25) and follicular carcinoma (FC, n = 10) and analysed them by means of receiver characteristics curves (ROC). Of 10 patients with FC, 8 (80%) patients presented a moderate increase of intranodular vascularization using power Doppler US. In contrast, the majority (84%, 21 out of 25 cases) of FA cases showed only a peripheral rim of color flow even by power Doppler US. These color flow imagings by power Doppler US were suggested to be a reliable tool for the differential diagnosis of thyroid follicular tumor with a sensitivity of 87.5% and a specificity of 92%. In velocimetric analyses, the Vmax/Vmin ratios, PI, and RI were significantly higher in the patients with FC than those with FA (p<0.001, p<0.005, and p<0.001, respectively). By means of ROC, FC could be diagnosed with a cutoff value of ratio of PI (>1.35), RI (>0.78), and Vmax/Vmin (>3.79). The diagnostic efficiency evaluated by ROC curves were 0.898 for PI, 0.876 for RI, and 0.888 for Vmax/Vmin, respectively. In conclusion, the evaluation of the vascular pattern and the velocimetric parameters using pulsed and power Doppler ultrasound may provide important information that is useful in making correct differential diagnosis of malignant or benign thyroid follicular tumor preoperatively.

Adenocarcinoma, Follicular↗
PubMed2005

Rapid differential diagnosis of Graves' disease and painless thyroiditis using total T3/T4 ratio, TSH, and total alkaline phosphatase activity.

When thyrotoxic patients are first seen in an outpatient clinic, it is important to make a differential diagnosis of Graves' disease (GD) and painless thyroiditis (PT). Using the three parameters of total T3/T4 ratio, TSH and T-ALP activity, all of which can be obtained within one hour in our hospital, 173 untreated patients with thyrotoxicosis were evaluated for the ratio of each parameter. For GD vs. PT, total T3/T4 (ng/microg) ratio (>20), TSH (<0.005 microU/ml) and elevated T-ALP had a likelihood ratio of 2.14, 2.12 and 4.07, respectively. When a patient had all three positive parameters, the likelihood ratio increased to 5.81, which showed effective synergy. These data suggest that, in addition to total T3/T4 ratio and TSH value, T-ALP activity is a useful parameter for the rapid differentiation of GD. The lower T-ALP activity seen in PT is probably due to the fact that patients develop less severe thyrotoxicosis or visit hospital earlier than patients with GD. Therefore, the diagnostic accuracy for Graves' disease might be increased by using the three parameters in combination.

Adult↗
PubMed2005

Ampulla cardiomyopathy after hypoglycemia in three young female patients with anorexia nervosa.

Ampulla cardiomyopathy is named after the echocardiographic abnormalities occurring in this condition, characterized by extensive akinesis (ballooning ) of the apical region with hypercontraction of the basal segment of the ventricle. We describe 3 young female anorexia nervosa patients showing evidence of this cardiac complication after hypoglycemia. One case was complicated by echocardiographically confirmed ampulla cardiomyopathy while the other 2 patients showed increases in myocardial enzymes and transient electrocardiographic abnormalities consistent with this complication. The precipitating event for all three patients was hypoglycemic coma, and this is the first case report in which this factor lead to the complication of ampulla cardiomyopathy in anorexia nervosa patients.

Adolescent↗