Effect of lithium on thyroidal 131iodine uptake, its clearance, and circulating levels of triiodothyronine and thyroxine in lead-treated rats

The influence of lead acetate (50 mg per kg body weight) on the 131iodine (131I) biokinetics (uptake and retention) in rat thyroid and serum levels of triiodothyronine (T3) as well as thyroxine (T4) was evaluated as a function of time and in combination with lithium treatment. The 2-h and 24-h uptake of 131I in the thyroid was stimulated significantly by lead treatment. The 24-h uptake showed a maximum stimulation after 4 months of lead treatment. Lithium supplementation, however, showed the opposite effect by reducing the iodine uptake whereby the maximum decrease was noticed after 2 months of treatment. Further, simultaneous lead and lithium treatment resulted in an even more pronounced increase of 2-h 131I uptake with a maximum after 3 months. However, the 24-h uptake after 3 months and 4 months of treatment did not differ significantly from the lead treated reference groups. The thyroidal biological half-life of 131I (Tbiol) was found to have clearly increased following the lead/lithium treatment. Interestingly, the combined lead/lithium treatment applied for 4 months caused a further growth of Tbiol, thus reflecting an increased retention of 131I. A maximum increase of Tbiol was seen after 2 months of combined treatment. A progressive decline of the circulating T3 and T4 levels following lead or lithium treatment was noticed and was more pronounced after combined treatment.     

碘131 与抗甲状腺药物治疗甲亢的临床疗效比较

目的:探讨碘131(I131)和抗甲状腺药物治疗甲亢的临床疗效对比,为临床提供参考依据。方法:选择2012年1月至2014年10月我院甲状腺功能亢进患者218例,按照随机数字表法分为观察组和对照组,每组各109例患者,观察组采用碘131治疗,对照组采用抗甲状腺药物治疗。比较治疗12个月后两组患者的临床疗效、复发率和并发症,采用酶联免疫吸附法检测治疗前后血清甲状腺激素水平。结果:治疗12个月后,观察组的有效率为92.66%明显高于对照组的69.72%,观察组的复发率为2.75%明显低于对照组的13.76%,差异均有统计学意义(P0.01)。观察组的心脏病、肝功能受损及血象降低等不良反应的发生率为7.34%明显低于对照组32.11%,差异有统计学意义(P0.01)。治疗后两组患者的血清甲状腺素(T4)、游离三碘甲状原氨酸(FT3)、三碘甲状原氨酸(T3)、促甲状腺激素(TSH)、游离甲状腺素(FT4)水平较治疗前降低,且观察组的降低幅度优于对照组,差异均有统计学意义(P0.05)。结论:碘131治疗甲亢可提高临床疗效,降低复发率,不良反应轻,可降低血清甲状腺激素水平,,值得推广应用。     

食盐加碘后甲状腺摄 ~（131）I率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I率的变化及其与24小时尿碘含量的相关性,探讨甲状腺摄131I率与碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I率的变化,分析健康体检者甲状腺摄131I率、晨尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6及24小时甲状腺摄131I率均显著降低;健康体检者甲状腺摄131I率与24小时尿碘含量呈负相关（r=-0.7651,P〈0.001）,晨尿碘浓度与24小时尿碘含量呈正相关（r=0.8231,P〈0.001）,经肌酐校正的尿碘含量与24小时尿碘含量呈正相关（r=0.9054,P〈0.001）。结论：食盐加碘对甲状腺摄131I率有显著影响,应重新确立甲状腺摄131I率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

食盐加碘后甲状腺摄131I 率的变化及其与尿碘的关系

目的：了解食盐加碘后健康人及甲亢患者甲状腺摄131I 率的变化及其与24 小时尿碘含量的相关性,探讨甲状腺摄131I 率与 碘营养状况的关系。方法：对比食盐加碘前后健康体检者及甲亢患者甲状腺摄131I 率的变化,分析健康体检者甲状腺摄131I 率、晨 尿碘浓度及经肌酐校正的尿碘含量与24小时尿碘含量的相关关系。结果：健康人及甲亢患者食盐加碘后3、6 及24 小时甲状腺 摄131I 率均显著降低;健康体检者甲状腺摄131I 率与24 小时尿碘含量呈负相关（r=－0.7651, P<0.001）,晨尿碘浓度与24 小时尿碘 含量呈正相关（r=0.8231, P<0.001）,经肌酐校正的尿碘含量与24 小时尿碘含量呈正相关（r=0.9054, P<0.001）。结论：食盐加碘对甲 状腺摄131I 率有显著影响,应重新确立甲状腺摄131I 率的正常范围及甲亢的诊断标准;经肌酐校正的尿碘含量较晨尿碘浓度能更 准确地反映碘营养状况;甲状腺摄131I率可作为评估个体碘营养状况的指标,可以稳定地反映近期的碘营养状况。     

Membrane reception of thyroid hormones]

Comparative and competitive analyses of thyroxine (T4) and triiodothyronine (T3) binding to highly purified rat liver, brain and lung cell plasma membranes were carried out. The dependence of hormone binding on the time, temperature and concentration was studied. The effects of trypsin and partial delipidation on the binding parameters of thyroid hormones were investigated. Two thyroid hormone-binding sites were detected in cell plasma membranes of all tissues under study. The maximal binding of T4 to rat liver membranes and the maximal binding of T3 to rat brain membranes was observed in all experiments, the affinity for T3 being higher than that for T4. An important role of both protein and lipid components of plasma membranes in the membrane reception of thyroid hormones is proposed.     

Study of trace elements in blood of thyroid disorder subjects before and after 131I therapy

Both trace elements and thyroid hormones play essential roles in the human body. However, the previous results about the interaction between these two factors are often controversially given. In order to make clear the influence of thyroid hormones on the homeostasis of trace elements, we studied the variation of Fe, Cu, and Zn in erythrocyte and serum from patients with hyperthyroidism before and after 131I therapy by the X-ray fluorescence method. The different thyroid statuses of the patients before and after the therapy were assayed by determining the levels of thyroid hormones. The results showed that the homeostasis of metal ions in both serum and erythrocyte could be more or less influenced by the altered thyroid hormones. The serum Cu and Zn exhibited the significantly positive correlation with triiodothyronine (T3) and thyroxine (T4). Although the serum Cu and Zn differed significantly before and after the therapy, no difference was observed in the concentrations of Cu and Zn in erythrocyte, except that the erythrocyte Zn in the patients with hypothyroidism exhibited an obvious increase. Furthermore, the erythrocyte Zn showed a markedly negative correlation with T3.     

Inhibition of thyroidal cyclic AMP-dependent protein kinase by thyroid hormone.

Bovine thyroid cyclic AMP-dependent protein kinase was purified by DEAE-Sephadex and Sephadex G-200 chromatography. This preparation showed a 240-fold increase in specific activity over the initial 20,000 x g supernatant with histone as substrate and 1 micronM cyclic AMP in the assay mixture. In the presence of 2.5 X 10(-5)M L-triiodothyronine (T3), protein kinase activity was significantly reduced; 50% inhibition was achieved at 1 X 10(-4) M. Tests of diverse thyroid hormone analogs showed that T3 and its derivatives were more potent inhibitors than T4 and its derivatives which, in turn, were more potent than thyronine or diiodothyronine. Mono- and diiodotyrosine, tyrosine, and iodide were without effect. Triiodothyronine did not inhibit kidney, spleen, or lung protein kinase activity. The magnitude of the inhibition was the same whether or not cyclic AMP (1 micronM) was present in the incubation mixture, suggesting an effect on the catalytic, rather than the regulatory subunit of the enzyme. The inhibition of protein kinase by thyroid hormone was not influenced by Mg++ concentration but was overcome in a competitive manner by increasing ATP concentration. Increasing the histone concentration did not modify the inhibition. Although these studies suggest a novel cellular control mechanism, the high thyroid hormone concentrations required and the lack of concordance between inhibitory effects and biologic activity of the analogs tested precludes assumption of physiologic relevance.     

Chemical determination of iodinated compounds in human thyroid

As a tool with which to detect iodinated compounds in human thyroid specimens, we have reevaluated a nonincineration technique which has so far been employed in the determination of thyroxine-iodine in peripheral blood. The catalytic action of iodoamino acids in the Ce-As reaction was enhanced by a small amount of Cl2. On the contrary, a large amount of Cl2 inhibited the reaction unexpectedly. Among iodide, iodotyrosine and iodothyronine, iodide was the most effective catalyst in the Ce-As reaction and iodothyronine was the least effective one. Protein seemed to inhibit this reaction of thyroglobulin. But the result of iodine content in thyroglobulin by this technique agreed well with that by incineration when measured 127I was corrected by percent activity of dializable part of the total activity of 131I-thyroglobulin with the same protein concentration, after the NaClO treatment. The results of human thyroid specimens were as follows: the thyroglobulin content of five normal subjects was 8.0 +/- 1.5% of wet thyroid weight. That of Hashimoto's disease was significantly decreased which seemed compatible with the decrease in iodine content of thyroglobulin, whereas thyroglobulin content of Graves disease treated with 1-methyl, 2-mercaptoimidazole followed by a large dose of iodide was well preserved in spite of a lower degree of iodination of thyroglobulin. As for the distribution of iodoamino acids-iodine in normal thyroid, T4 was 20.5 +/- 0.7%. This technique ultimately looks promising as a tool with which to study intrathyroidal iodine metabolism in human.     

Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma

INTRODUCTION: The loss of iodine uptake by differentiated thyroid carcinoma (DTC) cells is a major therapeutic problem especially in patients with nonsurgical metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted to retain iodine uptake as a result of redifferentiation (influence by retinoic acid receptors present in DTC cells). MATERIAL AND METHODS: Between 1999 and 2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were treated twice - 13 treatment cycles in total). Side effects in skin and mucous membranes were observed in all the patients, however, their intensity did not require termination of the therapy. RESULTS: Increase of iodine uptake was observed in 5 patients (45%). Decreased Tg concentration was observed in 9 patients. In that group, increased (131)I uptake was observed in 4 patients with distant metastases. All determinations of Tg concentrations were carried out under TSH stimulation. CONCLUSIONS: 13-cis-retinoic acid causes an increase of radioiodine uptake in around half of treated patients, however, the follow-up of these patients indicates that this increase does not result in either full remission or even stabilisation of neoplastic disease. The possibility should be considered to use cis-retinoic acid as an independent therapeutic approach in patients with radioiodine non-avid foci of thyroid carcinoma especially those showing high expression of RARb and RXRg receptors.     

碘131与他巴唑治疗甲状腺功能亢进症的临床疗效比较

目的:观察和比较碘131与他巴唑治疗甲状腺功能亢进症的临床疗效及安全性。方法:选取2012年1月至2016年1月于我院确诊并治疗的甲状腺功能亢进患者282例,根据随机数字表法分为碘131治疗组和药物治疗组,碘131治疗组采用131I进行治疗,药物治疗组采用他巴唑口服治疗。比较两组患者的临床疗效,治疗前后血清TSH(thyroid stimulating hormone,促甲状腺激素)、FT(free triiodothyronine,游离三碘甲状腺原氨酸)、FT4(free thyroxine concentration assay,血清游离甲状腺素)水平及TRAb(TRAB thyrotropin receptor antibodies,促甲状腺激素受体抗体)阳性率的变化及治疗期间不良反应的发生情况(心功能、肝功能、肾功能、甲状腺功能下降、白细胞减少),并对患者进行6个月的随访,记录和比较患者甲亢复发情况。结果:治疗后,碘131治疗组的总有效率为92.9%,显著高于药物治疗组(64.5%,P0.05);两组患者血清TSH水平较治疗前显著升高,而血清FT3、FT4水平及TRAb阳性率均较治疗前显著降低(P0.05),且碘131治疗组血清TSH水平明显高于碘131治疗组,而血清FT3、FT4水平及TRAb阳性率明显低于碘131治疗组(P0.05);碘131治疗组复发率及总不良反应发生率均明显低于药物治疗组(P0.05)。结论:碘131对甲状腺功能亢进症的疗效优于他巴唑口服治疗,可明显增加血清TSH水平,降低血清FT3、FT4水平及TRAb阳性率,且患者复发率及不良反应发生率均较低。     

Diurnal rhythms of thyroid hormones in rooster chicks (Gallus domesticus). 3. Studies on the changes in deiodination rate of thyroxine-I-131]

As a measure for the availability and efficiency of the so-called free hormone to repress the thyreotropin-secretion (Mouriz et al., Endocr. 79, 248-260 (1966) we investigated the deiodination of thyroxine-I-131 (T4-I-131). This was done with special regard to a possible cyclic variation. By means of the reutilisation we could measure the removed radio-iodide in the thyroid 1-1/2 hours after T4-I-131 application. Using I-125 as a reference-isotope for the radioiodine uptake we could specify the actual extent of deiodination. The deiodination had a diurnal variation: The minimal values at 9 am and 9 pm ("deiodination" 10 or 9 percent) were significantly different (2 P less than 0.025) from the maximal values at 3.00 am and 3.00 pm ("deiodination-rate" about 17 percent). We propose the following explanation: 1) While the deiodination is decreasing in the morning and evening the pituitary releases more thyreotropin; 2) Thereby the thyroid releases more hormone and so the protein-bound iodine and the so-called free hormone raises. This would be in good agreement with our prior investigations.     

The effect of thyroxine and related compounds on the aerobic myeloperoxidase--catalysed oxidation of NADH

Thyroxine concentrations as low as 1 microM significantly stimulate compound III formation during aerobic oxidation of NADH by highly purified myeloperoxidase. This increased compound III formation is paralleled by an increased oxidation of NADH. Stimulation of various thyronine and tyrosine analogues was in the order T4 greater than T3 greater than 3,5-T2 (or triiodothyropropionic acid). Thyronine and diiodotyrosine had no significant effect. From the potencies of the various thyronines to stimulate compound III formation, the following structural features seem necessary: (1) Substitution of thyronine with four iodine atoms. (2) An amino group on the alanine side chain. (3) Both aromatic rings of thyronine.     

Decrease in triiodothyronine binding sites in chick embryo erythrocytes during early development

Specific thyroid hormone (TH) binding sites have been detected in nuclei of erythrocytes obtained from developing chick embryos. The binding characteristics and relative affinities for TH analogs were those expected of TH receptors. Nuclear triiodothyronine (T3) saturation analysis was carried out in vitro by incubating intact erythrocytes in M199 medium with 3-200 pM [125I]T3 for 1 hr at 37 degrees C or 20-24 hr at 21 degrees C. Nuclei were obtained by centrifugation after lysing the erythrocytes in a stabilizing buffer containing 0.3% saponin, followed by addition of Triton X-100 (final concentration 0.2%) to minimize the nonspecific binding. Scatchard analysis of equilibrium binding data suggested that the nuclei possess a single class of binding sites. The binding is reversible and the rate of dissociation is temperature dependent. T3 and T4 appear to bind to the same sites, but the affinity of T3 was 16 times greater. Among TH analogs tested, Triac had the highest affinity followed by L-T3, D-T3, Tetrac, L-T4, D-T4, T2, and rT3. Serial studies performed on different days of chick embryogenesis demonstrated a rapid and significant decrease of the erythrocyte nuclear T3 receptor. On Day 5, the number of T3 binding sites was maximal at 1600 +/- 100 per nucleus. The number declined steadily until, by Day 20, it had reached about 60 +/- 10 sites/nucleus. RBC from adult and baby chickens had less than 1% as many binding sites as those from Day 5 embryos. There was no significant change in the affinity of the sites (Kd approximately equal to 20 pM at 37 degrees C). The reason for the loss of T3 binding sites during embryogenesis is not known. Since the plasma level of the TH increases during embryogenesis, this may reflect down regulation. Another possibility is that the change in erythrocyte population which occurs during this period involves production of erythrocytes which contain fewer T3 binding sites.     

Lack of effects of thyroid hormones on human erythrocyte acetylcholine esterase

Effects of thyroid hormones and their metabolites such as L-T1, L-T2, L-T3 and L-T4 on human erythrocyte acetylcholine esterase were studied. The activity of the enzyme of intact erythrocytes was not affected by these hormones, though studied under various conditions. The physiological significance of the binding of these hormones to erythrocyte membranes remains unclear. Our results indicate that the acetylcholine esterase is not a suitable enzyme for cytochemical bioassay for thyroid hormones.     

Iodinated phospholipids and the iodination of proteins of dog thyroid gland in vitro

Slices of dog thyroid gland were incubated with liposomes consisting of (125)I-labelled phosphatidylcholine (the iodine was covalently linked to unsaturated fatty acyl chains). The (125)I label of (125)I-labelled liposomes was incorporated into thyroid protein and/or thyroglobulin at a higher rate than was the (131)I label of either Na(131)I or (131)I(2). The iodine was shown to be protein-bound by the co-migration of the labelled iodine with protein under conditions where free iodine, iodide and lipid-bound iodine were removed from protein. The uptake of iodine from the iodinated phospholipid was probably due to phospholipid exchange between the iodinated liposomes and the thyroid cell membrane, since (a) (14)C-labelled phospholipid was metabolized to (14)CO(2) and (b) many lipids in the tissue slice became (14)C-labelled. A very strong inhibition of iodide ;uptake' from Na(131)I, caused by thiosulphate, produced only a minor inhibition of the incorporation of (125)I from (125)I-labelled liposomes into thyroid protein and/or thyroglobulin. This implies that free iodide may not necessarily be formed from the iodinated phospholipids before their entrance or utilization in the cell. Synthetic polytyrosine polypeptide suspensions showed some iodination by (131)I-labelled liposomes. In tissues with low tyrosine contents, such as liver and kidney, only a trace uptake was observed. Salivary gland showed some uptake. Endoplasmic reticulum of thyroid gland showed a higher iodine uptake than that of the corresponding plasma membranes. These experiments, together with the demonstration of the diet-dependent presence of iodinated phospholipids in dog thyroid, leads us to suggest that iodination of the membrane phospholipids of thyroid cells may be directly or indirectly involved at some stage in the synthesis of thyroglobulin, or exists as a scavenger mechanism, to re-utilize and/or recover released iodine from unstable compounds inside the thyroid cell.     

Effects of Iodine-131 in sheep depending on the content of stable iodine in the diet]

The biological effect of 131I was studied in sheep kept on a diet deficient in stable iodine. An increased capture and accretion of iodine in the thyroid gland and in the whole body were observed. The disturbances in the structure and function of the thyroid gland, liver and haemopoietic organs were more pronounced in the animals kept on the iodine deficient diet.     

Diphasic effect of thyrotropin on the uptake and absorption of iodine-131 by thyroid cell culture]

The studies were performed on the primary culture of thyroid cells of newborn pigs. It was shown that thyroid-stimulating hormone (TSH) within the first 12th of its action inhibited uptake and organification of iodine-131. A negative influence of TSH on 131I uptake was retained both with its simultaneous introduction into the culture medium and with 30 min interval as well as when conducting experiments on the 1st, 3d, 5th and 7th days of cultivation. Previous 72h incubation with TSH sufficient for activation of all the links of iodine transport caused an increase in 131I uptake and organification.     

Process of iodination of thyroglobulin and its maturation. I. Properties and distribution of thyroglobulin labeled with radioiodine in pig thyroid slices.

Pig thyroid slices were incubated with Na131I and the 17--19S 131I-labeled thyroglobulin isolated was subjected to dissociation with 0.3 mM sodium dodecyl sulphate SDS) on sucrose density gradient centrifugation and to iodoamino acid analysis. During the incubation, initially dissociable thyroglobulin was gradually altered to 0.3 mM SDS-resistant species with increasing incorporation of iodine. Microsome-bound, poorly iodinated thyroglobulin and preformed thyroglobulin were chemically iodinated and then subjected to analysis of dissociability and iodoamino acid contents with newly incorporated iodine. The results indicated that the behavior of the former thyroglobulin resembled that of 131I-thyroglobulin obtained from the slices. Then, thyroid slices were incubated for 3 min with Na131I and 3H-leucine with or without 10-min chase incubation. The sucrose density gradient centrifugation patterns of 131I and 3H-radioactivity of cytoplasmic extracts indicated that 131I-thyroglobulin is contained in particulates, especially in vesicles with low density(d=1.12) and that some of them are released into the soluble fraction within 10 min. The vesicles contained peroxidase and NADH-cytochrome c reductase, and are probably exocytotic vesicles in the apical area of cytoplasm of follicular cells. No positive evidence was obtained that plasma membranes participate in the iodination of thyroglobulin under the present experimental conditions. These results suggest that, in the incubation of thyroid slices, iodine atoms are preferentially incorporated into newly synthesized, less iodinated thyroglobulin, rather than preformed thyroglobulin, and that the iodination occurs, at least to a certain degree, in apical vesicles before the thyroglobulin is secreted into the colloid lumen.     

Characterization of thyroxine-albumin binding using high-performance affinity chromatography II. Comparison of the binding of thyroxine,triiodothyronines and related compounds at the warfarin and indole sites of human serum albumin

High-performance affinity chromatography was used to examine the binding of thyroid hormones and related compounds at the warfarin and indole sites of human serum albumin (HSA). This was studied by continuously applying l-triiodothyronine (l-T₃), l-reverse triiodothyronine (l-rT₃) or structural analogs of these compounds to an immobilized HSA column while making injections of site-specific probe molecules (i.e. R-warfarin and l-tryptophan). The results were compared with those obtained previously for l-thyroxine (l-T₄). Equilibrium association constants and thermodynamic parameters measured by this approach showed good agreement with previous models reported for l-T₄ and l-T₃ at their high-affinity sites on HSA. This data confirmed that the phenol groups of l-T₄ and l-T₃ played a significant role in the binding of these compounds at the indole site. Work performed at the warfarin site and with other solutes (e.g. l-rT₃) indicated that additional factors, such as interactions through the thyronine backbone or terminal amine and carboxyl groups of these compounds, could also be involved in the binding of thyroid hormones to HSA.