Clinical and biochemical changes following I-131 therapy for hyperthyroidism in patients not pretreated with antithyroid drugs

Background: Radioiodine therapy (I-131) for the treatment of hyperthyroidism has been shown to be effective and safe. Despite the extensive experience with radioiodine therapy, the necessity for pretreatment with antithyroid drugs is controversial. Pretreatment is partly based on the concept that antithyroid drugs deplete the thyroidal hormonal stores, thereby reducing the risk of a radioiodine-induced aggravation of hyperthyroidism or thyroid storm. Few data are available on the frequency of clinically significant exacerbations of hyperthyroidism following I-131 therapy without prior treatment with antithyroid drugs. The aim of the present study was to determine prospectively the early clinical and biochemical changes after I-131 therapy in patients who were not pretreated with antithyroid drugs. Methods: Patients with Graves' disease (n = 21), toxic multinodular goiter (n = 11) or toxic adenoma (n = 2) were studied before and after I-131 therapy. Clinical and biochemical parameters of thyroid function were investigated before and 1, 2, 8, 11, 18 and 25 days after I-131 treatment. Patients were given no antithyroid drugs prior to I-131 therapy, all patients received beta-blocking agents for symptomatic relief. Results: In 19 of 34 patients, a transient increase in thyroid hormone levels was observed, predominantly in the first week following I-131 therapy. None of these patients experienced worsening of thyrotoxic symptoms. This transient increase in thyroid hormone levels was demonstrated in all patients with toxic multinodular goiter, whereas it was found in only six of 21 patients with Graves' disease. This difference could not readily be explained by differences in pretreatment thyroid hormone levels, administered dose or effectively absorbed dose of I-131. Conclusions: I-131 treatment of hyperthyroidism without pretreatment with antithyroid drugs may cause a transient increase in thyroid hormone levels. Clinically significant exacerbations of hyperthyroidism were, however, not observed in our study population. Increased hormone levels following I-131 therapy were more often seen in patients with toxic multinodular goiter than in patients with Graves' disease. (C) 1999 Elsevier Science B.V. All rights reserved

Reelin modulates cytoskeletal organization by regulating Rho GTPases

The correct positioning of postmitotic neurons in the developing neocortex and other laminated brain structures requires the activation of a Reelin-lipoprotein receptor-Dab1 signaling cascade. The large glycoprotein Reelin is secreted by Cajal-Retzius pioneer neurons and bound by the apolipoprotein E receptor family members Apoer2 and Vldl receptor on responsive neurons and radial glia. This leads to the tyrosine phosphorylation of the cytoplasmic protein Disabled-1 (Dab1) by non-receptor tyrosine kinases of the Src family. Various signaling pathways downstream of Dab1 connect Reelin to the actin and microtubule cytoskeleton. Despite this knowledge, a comprehensive view linking the different cell-biological and biochemical actions of Reelin to its diverse physiological roles not only during neurodevelopment but also in the maintenance and functioning of the adult brain is still lacking. In this review, we discuss our finding that Reelin activates Rho GTPases in neurons in the light of other recent studies, which demonstrate a role of Reelin in Golgi organization, and suggest additional roles of Cdc42 activation by Reelin in radial glial cells of the developing cortex