Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10-30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/ vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0-2 points), moderately differentiated (MD, 3-6 points) and poorly differentiated (PD, 7-10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08G0.17 and 5.33G0.43 (meanGS.E.M., P!0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (rZK0.438, P!0.01). The mean number of years until metastasis after the initial operation was 5.5G2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.

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Due to the likelihood of physical and mental health impacts following the unprecedented accident at the Fukushima Dai-ichi Nuclear Power Plant, the Fukushima prefectural government decided to conduct the Fukushima Health Management Survey to assist in the long-term health management of residents. This included thyroid ultrasound examination for all children in Fukushima. For appropriate evaluation of ultrasound screening of the thyroid, it is important to understand its reference data of thyroid findings in children in general. In order to analyze the frequencies of specific thyroid findings, we conducted ultrasound screening of the thyroid by the same procedures as used in Fukushima in 4,365 children, aged 3 to 18 years, from three Japanese prefectures. Overall, thyroid cysts were identified in 56.88% and thyroid nodules in 1.65% of the participants. Thyroid cysts and nodules with a maximum diameter of more than 5 mm were identified in 4.58% and 1.01%, respectively, and age-adjusted prevalences were 3.82% and 0.99%, respectively. Although the prevalence of cysts and nodules varied among the examination areas, no significant differences were observed among the three examination areas in the prevalence of cysts and nodules with a maximum diameter of more than 5 mm. Also, the prevalence of thyroid cysts and nodules, especially those with a maximum diameter of more than 5 mm, significantly increased with age, and showed a female predominance. We also identified ectopic thymus (1.95%), diffuse goiter (1.40%), ultimobranchial body (0.73%), lymph node swelling (0.21%) and thyroid agenesis (0.05%). This is the first ultrasound description of the age-adjusted prevalence of thyroid cysts and nodules, or of the prevalence of abnormalities other than cysts and nodules, such as ectopic thymus, in relation to age, in the general Japanese child population. We contend that this can provide relevant information for the Fukushima Health Management Survey and future population studies.

because of the Cushingoid appearance, with the characteristic features of central obesity, moon face, skin atrophy, purple striae and buffalo hump, and the clinical criteria are clear, a debate exists in the literature over the biochemical diagnosis of this disease [3]. Recently, the diagnostic criteria for Cushing's disease have been reported by the Ministry of Health, Labour, and Welfare of Japan [4]. In the guideline, the following endocrinological findings were considered as diagnostic criteria: 1) The presence of a Cushingoid appearance; 2) Evidence of autonomic or abnormal secretion of ACTH, such as (a) normal-high ACTH and cortisol levels, and (b) high levels of urinary excretion of free cortisol; 3) Screening tests show (a) incomplete suppression of cortisol (> 5 µg/dl) by a lowdose (0.5 mg) overnight dexamethasone suppression test (DST), (b) high cortisol levels (> 5 µg/dl) during night time sleeping, and (c) response of plasma ACTH levels to the desmopressin (DDAVP) test; 4) The dif- Abstract. We evaluated the usefulness and accuracy of diagnostic tests for adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome, based on our experience of 88 cases, including 73 cases with Cushing's disease, and 15 cases with ectopic ACTH syndrome (EAS). In our study, 0.5 mg of dexamethasone failed to suppress the morning cortisol secretion in 100% of cases with Cushing's disease and EAS. Plasma ACTH levels were significantly increased by desmopressin (DDAVP) in 86% of cases with Cushing's disease, especially in microadenomas (90%), while these levels were not affected in normal subjects. In EAS, 44% responded to DDAVP. Plasma ACTH levels were increased in response to the human corticotropin-releasing hormone (CRH) test in 100% of microadenomas and 73% of macroadenomas with Cushing's disease, but only in 27% of cases with EAS. A high dose (8 mg) of dexamethasone suppressed the morning cortisol secretion in 89% of microadenomas with Cushing's disease, and in 82% of all cases with Cushing's disease, while it did in only 20% of cases with EAS. Taken together, the 0.5 mg dexamethasone suppression test (DST) and DDAVP test are considerably useful for the screening of ACTH-dependent Cushing's syndrome. The CRH test and 8 mg DST would be effective for the diagnosis of Cushing's diseases, because our study shows a sensitivity of 81% in cases with Cushing's disease when these tests are considered together. These data were submitted to prepare the diagnostic criteria for Cushing's disease, suggested by the working group of the Ministry of Health, Labour, and Welfare of Japan.

Diabetes mellitus is frequently associated with coagulation disorders such as coronary heart disease or stroke. We aimed to clarify the molecular mechanism whereby hyperglycemia causes the procoagulant state. The HuH7 human hepatocyte cells were treated with high glucose alone, or in combination with proinflammatory cytokines, and the effects on the activity of the transcription factor NF-B, which mediates the expression of acute phase and coagulation-related genes, were examined. The results showed that increasing the medium glucose concentration from 3 to 24 mM significantly enhanced the NF-B-luciferase activity by 40% in the presence of insulin. The effect was promoter-specific, and was not mimicked by comparable hyperosmolality with L-glucose. Proinflammatory cytokines such as interleukin-1 and TNF-also stimulated NF-B-dependent transcription, and showed an additive effect with high glucose. Similar effects were obtained on acute phase or coagulation/fibrinolysis-related gene promoters such as fibrinogen or PAI-1, all of which are shown to have NF-B-mediated transcription. Finally, pretreatment of the cells with an antioxidant PDTC completely abolished the effect of high glucose, and markedly attenuated that of TNF-, suggesting the involvement of reactive oxygen species. These results suggest that 1) high glucose as well as proinflammatory cytokines have positive effects on NF-B-mediated transcription in an additive manner, and enhance coagulation-related gene expression, and 2) the effects are mediated, at least partly, by the generation of oxidative stress, and may be responsible for the high prevalence of thrombotic disorders in the metabolic syndrome with diabetes, hyperinsulinemia, obesity and/or inflammation.