Crosstalk Between cAMP and Phosphoinositide System in Signal Transduction Pathways Through TSH Receptor / 대한내분비학회지

BACKGROUND: TSH stimulates both the adenyl cyclase and phospholipase C (PLC) pathways by binding to a single cell surface receptor that is coupled to G protein, and we examined crosstalk between these two signaling pathways. METHODS: FRTL-5 rat thyroid cells were grown in 6H medium, then incubated with 5H medium before the stimulation. Then cells were incubated for 24 hours with 5H mix containing 1 mCi/L myo-(2-N-3H) inositol. After pretreatment of 100 microM Rp-cAMP, 100 microM forskolin, 50 nM staurosporine, or 100 nM PMA (phorbol-12-myristate-13-acetate), TSH were added in different experiments. After 30 min at 37 degrees C, cells were disrupted and IP formation was determined. RESULTS: Stimulation with 100 microU/mL TSH resulted in a 1.65 fold increase in IP generation. In pursuing the possibility that the two post-receptor events might be linked in some way, we examined the effect of exogenously administrated Rp-cAMP, protein kinase A antagonist, and forskolin, a direct stimulant of protein kinase A, on IP generation achieved at a dose of 100 microU/mL TSH. The pretreatment of 100 M Rp-cAMP at a concentration sufficient to inhibit protein kinase A enhanced TSH-induced IP production. This effect of Rp-cAMP was dose-dependent. Forskolin attenuatedTSH-stimulated increases in phosphatidylinositide turnover. PMA, a protein kinase C (PKC) activator and staurosporine, a PKC inhibitor did not affect TSH-induced IP generation. CONCLUSION: These data suggested that activation of adenylate cyclase/cAMP post-receptor signalling casacde, which results in the protien kinase A activation, has an inhibitory effect on IP turnover activated by TSH.

Diagnostic Significance of Serum Thyroglobulin Measurement in the Follow - up of Patients with differentiated Thyroid Cancer / 대한내분비학회지

BACKGROUND: Although serum thyroglobulin (Tg) has been proved to be a good tumor marker in the follow-up of the well differentiated thyroid cancer, some patients show low detectable Tg with negative 131I scan. In the present study, we tried to determine the lowest level of serum Tg which suggests requirement of aggressive work-up for the recurrent or metastatic thyroid cancer. METHODS: Serum Tg levels were measured in 102 patients with well differentiated thyroid cancer who had underwent thyroidectomy followed by 131I ablative therapy. Of 102 patients, 44 patients had no remnant thyroid tissue, while 58 patients had remnant thyroid. Serum Tg levels were measured while TSH-suppressive dose of T4 was administered (on T4 therapy) and then T4 was discontinued for 4 weeks to increase serum TSH level (off T4 therapy), then serum Tg levels were analyzed in relation to the presence or absence of recurrent or metastatic thyroid cancer, assessed by I scan and operation with reference to the physical examination, chest X-ray and thyroid ultrasonogram. RESULTS: Of 102 patients, 16 patients were found to have recurrent or matastatic thyroid cancer. Among them, 10 patients didnt have any remnant thyroid, while 6 patients had remnant thyroid. Serum Tg was undetectable on T4 therapy in 6 patients, but rose higher than 30 ng/mL off T4 therapy in 2 patients, while Tg remained undetectable in other 4 patients. In all 10 patients whoseTg levels were higher than 1 ng/mL. on T4 therapy, Tg rose higher than 30 ng/mL off T4 therapy. The best cut-off value of serum Tg which suggests recurrent or metastatic disease in patients without remnant thyroid was 3 ng/mL on T therapy (sensitivity 60%, specificity 91%, accuracy 84%) and 30 ng/mL off T4 therapy (sensitivity 80%, specificity 75%, accuracy 77%). In patients with remnant thyroid, cut-off value of serum Tg could not be determined because of the low sensitivity and specificity. CONCLUSION: In patients with well differentiated thyroid cancer who have no remnant thyroid, serum Tg level lower than 3 ng/mL on T4 therapy can warrant following-up of patients only with such clinical measures only such as physical examination and thyroid ultrasonogram. However, patients with Tg level of 3 ng/mL or more requires Tg measurements off T4 therapy and 131I scan to evaluate the possibility of recurrent or metastatic thyroid cancer.

Changes in pulmonary ventilatory function in patients with thyrotoxicosis / 대한내과학회지

OBJECTIVE: Dyspnea is a common symptom in patients with thyrotoxicosis, which may be caused by several mechanisms including pulmonary ventilatory dysfunction. There have been controversies among studies on changes in pulmonary ventilatory function in thyrotoxicosis. We were to evaluate the changes in pulmonary ventilatory function in patients with thyrotoxicosis. METHODS: We measured the pulmonary ventilatory function with spirometry in 32 thyrotoxic patients with Graves' disease and in 22 age, sex-matched euthyroid control subjects. The changes in ventilatory function after treatment were evaluated in 18 thyrotoxic patients who became euthyroid with antithyroid drug treatment. RESULTS: 1) Forced vital capacity(FVC) was significantly lower in thyrotoxic patients compared to control subjects(3.06+/-0.68 L and 3.35+/-0.55 L, respectively, p<0.05). Percent predicted values of FVC showed similar results; 82+/-16 % in patients and 95+/-11 % in control subjects(p<0.05).2) Forced expiratory volume for 1 sec.(FEV1.0), forced expiratory flow 25-75(FEF 25-75) and FEF 50 were not different between patients and control subjects. FEV1.0/ FVC ratio were higher in thyrotoxic patient than in control(88+/-7 % vs. 84+/-8 %, p<0.05). 3) Serum thyrotropin binding inhibitor immunoglobulin (TBII) activities were significantly correlated with pretreatment FVC values(R=-0.45, p<0.05) and with FEV1.0 values(R=-0.41, p<0.05) in thyrotoxic patients. However, serum thyroid hormone concentrations had no correlations with FVC or with FEV1.0 values. 4) FVC, FEV1.0 of thyrotoxic patients increased, and FEV1.0/FVC ratio decreased sifnificantly after treatment of thyrotoxicosis in patient group. Numbers of patients with normal, mild, moderate, severe restrictive disease were 10, 4, 3, 1, respectively before treatment, which became 14, 2, 2, 0 after treatment of thyrotoxicosis in patient group. CONCLUSION: Ventilatory disturbances of restrictive pattern were common in thyrotoxic patients that were partially reversible after treatment of thyrotoxicosis. Such changes may be one of mechanisms causing dyspnea in thyrotoxic patients. The fact that decrease in FVC were significantly associated with serum TBII activities (thyroid autoantibody), but not with degree of thyrotoxicosis suggests that autoimmune process itself is involved in the development of pulmonary function abnormalities observed in those patients.