No abstract

Ultrasonography can be a sensitive and accurate method for preoperative localization of enlarged parathyroid glands in primary hyperparathyroidism, comparable in overall utility to sestamibi scintigraphy. These results suggest that a strategy of initial testing with one or the other method, followed by the alternate imaging test if the first test is negative, would provide correct parathyroid imaging in most patients without prior parathyroid surgery.

We have found that women with polycystic ovary syndrome (PCOS) have decreased sensitivity and responsiveness to insulin. The present study was performed to determine whether this impaired insulin responsiveness was associated with diminished GLUT-4 glucose transporter content in adipocytes. Insulin-stimulated glucose transport and GLUT-4 abundance were measured in abdominal adipocytes from obese (n = 9) and lean (n = 7) PCOS as well as obese (n = 8) and lean (n = 8) control women matched for age and weight. No woman had impaired glucose tolerance. The maximal insulin-stimulated increment in adipocyte glucose transport was independently decreased by obesity and by PCOS. As expected, GLUT-4 content in adipocyte membranes was decreased in obesity (by 40%, P < or = 0.01). GLUT-4 content was also significantly decreased in PCOS (by 36%, P < or = 0.01), independent of obesity. There was a highly significant correlation (R = 0.66, P < = 0.001) between GLUT-4 content and insulin-stimulated glucose transport in adipocytes from individual women across the study population. We conclude that the diminished adipocyte insulin responsiveness in PCOS is associated with decreased GLUT-4 abundance. This represents a newly recognized phenotypic feature of the insulin resistance of PCOS. Moreover, in human adipocytes, GLUT-4 abundance is highly correlated with insulin responsiveness.

Human and monkey brain sections were examined by immunohistochemical light and electron microscopy to determine the distribution of GLUT1, a glucose transporter isoform associated with erythrocytes and endothelial cells of the human blood-brain barrier. Protein immunoblotting of fractionated human brain membranes was performed to determine the distribution of molecular forms of the transporter. GLUT1 staining was abundant in erythrocytes and cerebral endothelium of gray and white matter but was also present diffusely in gray matter neuropil when viewed by light microscopy. Immunoelectron microscopy confirmed the gray matter and vascular localization of GLUT1, with specific GLUT1 staining seen in erythrocytes, gray and white matter endothelial cells, astrocyte foot processes surrounding gray matter blood vessels, and in astrocyte processes adjacent to synaptic contacts. No astrocytic staining was identified in white matter. Astrocyte GLUT1 staining was identified only in mature gray matter regions; undifferentiated regions of preterm (22-23 weeks gestation) cortex had GLUT1 staining only in blood vessels and erythrocytes, as did germinal matrix. Immunoblots of adult human frontal cortex revealed that two forms of GLUT1 (45 and 52 kDa) were present in unfractionated brain homogenates. Immunoblots of vessel-depleted frontal lobe revealed only the 45 kDa form in gray matter fractions, and depleted in membranes prepared from white matter regions. We conclude that the GLUT1 isoform of glucose transporter is present both in endothelium of the blood-brain barrier and in astrocytes surrounding gray matter blood vessels and synapses. Furthermore, the form present in astrocytes is likely to have a lower molecular weight than the form found in cerebral endothelium. The GLUT1 transporter may play an important role not only in astrocyte metabolism, but also in astrocyte-associated pathways supporting neuronal energy metabolism.

Malignant cells exhibit increased rates of glycolysis and glucose uptake, the latter of which is mediated by glucose transport proteins. Because several types of cancer have been shown to express high levels of the GLUT1 glucose transporter isoform, we hypothesized that expression of GLUT1 might distinguish malignant from benign thyroid tissue. Archival thyroid tissue obtained at surgery was immunostained for GLUT1 protein. There were 38 benign cases (24 follicular adenoma, 1 Hürthle cell adenoma, 8 nodular goiter, 3 Hashimoto's thyroiditis, 2 Graves' disease) and 28 cases of thyroid cancer (17 papillary and its follicular variant, 6 follicular, 1 Hurthle cell, 2 anaplastic, 2 medullary). Normal thyroid tissue adjacent to nodules showed no thyrocyte staining in any case. No GLUT1 staining was seen in thyrocytes in benign nodular tissue, except for a single case of Hashimoto's thyroiditis in which a few Hurthle cells showed weak staining. Among the thyroid cancers, 13 of 28 (46%) showed tumor cell GLUT1 staining in at least some areas. This included 9 of 17 cases of papillary carcinoma and its follicular variant, 2 of 6 cases of follicular carcinoma and 2 of 2 cases of anaplastic carcinoma. Tumor cell GLUT1 staining was seen in two patterns: circumferential plasma membrane staining focally within the tumor, or asymmetric staining of the basilar aspect of tumor cells adjacent to stroma in some cases of papillary carcinoma. We conclude that GLUT1 expression is frequently detectable by immunostaining in thyroid cancer, but not in benign nodules or normal thyroid. GLUT1 expression may be a clinically useful molecular marker for thyroid cancer.