Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter.

In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all patients before therapy and became positive in 4 patients. Hyperthyroidism developed in 3 of these 4 patients between 23 and 25 wk after therapy. In conclusion, in patients with nodular goiter pretreatment with a single, low dose of rhTSH allowed approximately 50-60% reduction of the therapeutic dose of radioiodine without compromising the efficacy of TV reduction.

Levels of plasminogen activators and their inhibitors in maternal and umbilical cord plasma in severe preeclampsia.

OBJECTIVE: The purpose of this study was to evaluate the plasminogen activator system in maternal and umbilical cord plasma in patients with severe preeclampsia compared with control subjects with normotensive pregnancies. STUDY DESIGN: Maternal blood was sampled from 42 patients at a median gestational age of 32 weeks; after delivery, arterial and venous umbilical cord blood was sampled from 37 and 36 of these patients, respectively. Maternal blood from women with uncomplicated pregnancies was sampled at the gestational age of 32 weeks (n = 18, group I), and umbilical cord blood was sampled after premature deliveries of normotensive pregnancies (n = 5, group II). Data were analyzed with the use of Mann-Whitney U tests. RESULTS: Patients had significantly higher tissue plasminogen activator (P <.01) and unchanged urokinase plasminogen activator plasma levels compared with control subjects at 32 weeks of gestation; lower plasminogen activator inhibitor type 2 (P < 0.01) and no different plasminogen activator inhibitor type 1 concentrations were observed compared to control subjects at 32 weeks of gestation. In the arterial and venous umbilical cord plasma of patients, plasminogen activator inhibitor type 1 levels were significantly higher(P <.01) compared with control subjects at 32 weeks of gestation, although urokinase plasminogen activator levels in arterial and venous umbilical cord plasma (P < 0.01) were significantly lower. CONCLUSION: Lower plasminogen activator inhibitor type 2 levels are associated with placental insufficiency, and higher tissue plasminogen activator levels are associated with endothelial dysfunction in patients with severe preeclampsia. The higher plasminogen activator inhibitor type 1 levels and lower urokinase plasminogen activator levels in umbilical cord of these patients are suggestive of decreased fibrinolysis in the fetal circulation.