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In a patient with one or more thyroid nodules larger than 10 mm in diameter, the likelihood of thyroid cancer per patient is independent of the number of nodules, whereas the likelihood per nodule decreases as the number of nodules increases. For exclusion of cancer in a thyroid with multiple nodules larger than 10 mm, up to four nodules should be considered for FNA. Sonographic characteristics can be used to prioritize nodules for FNA based on their individual risk of cancer.

SummaryReperfusion ofischemic tissue induces an acute inflammatory response that can result in necrosis and irreversible cell injury to both local vascular endothelium and parenchyma. To examine the pathogenesis of ischemia/reperfusion injury, we have used mice deficient in complement components C3, C4, or serum immunoglobulin in a hindlimb model of ischemia. We found that mice homozygous deficient in C3 or C4 were equally protected against reperfusion injury based on a significant reduction in leakage of radiolabeled albumin out of the vasculature. This demonstrates that classical pathway complement is an important factor in the initiation ofinflammarion following reperfusion. Furthermore, mice deficient in serum immunoglobulin were equally protected and this protection could be reversed by reconstitution with serum from norreal mice. Thus, this report describes a novel mechanism for reperfusion injury that involves antibody deposition and activation of complement leading to inflammation permeability. While the pathogenesis of reperfnsion injury is not completely understood, the complement system is thought to be involved since there is clear evidence of deposition of complement components C5-9 after repeffusion of hypoxic tissue (1, 2) and injury can be inhibited in part by pretreatment with soluble complement receptor type 1 (sCR1) (3-6). Weisman et al. found that pretreatment with sCR1 substantially reduced influx of neutrophils, deposition of C5-9 and myocardial infarct size in a rat model of myocardial ischemia (3). Similar studies have used sCR1 to block or reduce inflammation after reperfusion ofischemic rat hindlimb or intestine and of mouse skeletal muscle (cremaster) (4-6). Complement receptor type 1 (CR1; CD35), which is normally expressed by human erythrocytes, B lymphocytes, granulocytes, and macrophages, binds activated C3 (C3b) and C4 (C4b) leading both to dissociation of the complement system's C3 and C5 activating enzymes and to proteolytic degradation of C3b and C4b by serum factor I. When administered in a soluble form, recombinant sCR,1 functions as a highly effective inhibitor of serum complement activation (7).To clarify the role of complement and gain insight into the pathogenesis of ischemia/reperfusion injury, we have examined novel strains of mice deficient in either complement components C3 or C4 in a mouse model ofhindlimb ischemia reperfusion. Both strains of mice were equally protected from vascular injury demonstrating that injury is mediated by the classical pathway. Moreover, mice totally deficient in antibody, i.e., recombination-activation gene 2 deficient (RAG-2-/-) (8), were equally protected and protection could be abrogated by reconstitution with fresh mouse serum. These results support the hypothesis that ischemia/reperfusion injury is initiated by natural antibody binding to hypoxic endothelium and activation of the complement system. Materials and MethodsReconstitution of Antibody-d!ficient Mice. RAG2-/-mice were reconstituted by i.v. administration of 0.5 ml of pooled ...