The changes of in vitro 131I-iodine uptake in the thyroid gland of rats exposed to septal lesions and immobilization stress.

The in vitro uptake of 131I by the thyroid gland was investigated in rats after immobilization stress with special respect to animals lesioned in the septal area. Lesions in a septal area performed 10 days before decreased the iodide accumulation in the thyroid, while stress by immobilization increased it to the control basal value. Repeated immobilization in control rats did not produce any changes in the iodide uptake in vitro. ACTH injected in vivo stimulated the iodide 131I uptake in vitro by thyroid glands of hypophysectomized rats. It is concluded that immobilization stress in rats with septal lesions increases 131I-iodide uptake in vitro and that the increase was probably influenced by both catecholamines and glucocorticoids.     

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.     

Influence of initial large dose on subsequent uptake of therapeutic radioiodine in thyroid cancer patients

Fifty-two patients with differentiated thyroid cancer, following thyroidectomy were studied by administering a quantity of up to 5 mCi of [¹³¹I]sodium iodide. In most of these patients, radioiodine uptake values obtained with the subsequent therapeutic dose were markedly lower than those observed with the initial doses. This observation was verified in seven of the patients with differentiated thyroid cancer, by measuring the radioiodine uptake with a second dose of 4.5 mCi of [¹³¹I]sodium iodide. Calculations showed that the major etiology was probably therapeutic irradiation of the thyroid by the first dose.     

Effect of short-term and long-term lithium treatment on uptake and retention of iodine-131 in rat thyroid

No significant change occurred in the uptake by the thyroid of male Wistar rats of a standard dose of carrier-free 131I administered intraperitoneally and its retention by the thyroid, as measured by biological and effective half-life, after feeding these rats a powdered pelleted diet containing lithium carbonate (1.1 g per kg of diet) for 7 days. However, continuing this diet for 10 days inhibited thyroid uptake and increased the retention of 131I. Uptake remained suppressed for up to 4 months after lithium treatment and continuing this treatment for 6 months did not result in any significant change in 131I uptake by the thyroid. Lithium treatment for 10 days increased the biological and effective half-life of 131I in the thyroid and this increase continued for the 6 months treatment period. The dose of 131I delivered to the thyroid was significantly lower after 10 days and 1 month of lithium treatment but there was no change in this dose after 2 and 4 months of treatment. However, there was a significant increase after 6 months.     

Inhibition of thyroid function and thyrotrophic activity following the administration of methallibure (ICI-33 828).

1. Goitrogenic action of methallibure (ICI-33828) has been studied in mice gerbil and hedgehog using thyroid weight and histological structure as an index. Liquefaction and vacuolation of thyroid follicles were most prevelant after methallibure administration. 2. The I131 content of the thyroid gland was significantly higher in the methallibure treated groups than in the controls. This denotes a decrease in the rate of discharge of thyroid hormone. 3. Protein bound radioiodine (Pb I131) was low after methallibure administration. 4. Methallibure administration brings about hypertrophy of pituitary thyrotrophs which is also reflected in the increased basophilic cell percentage in gerbil (control: 15.5 percent; methallibure: 22.8 percent). 5. It is concluded that methallibure acts on thyroid function both by a direct effect on the gland as well as by influencing pituitary thyrotrophic activity in enhancing I131 uptake.     

Effect of long-term injection of high doses of potassium iodide on iodine metabolism in rat thyroid gland

Concentration of thyroid hormones in the serum of the rats after 14-day injections of potassium iodide (1, 3, 10, 100, and 500 physiological daily doses) did not differ from the control values. Excessive administration of potassium iodide increased the total iodide content in the rat thyroid tissue by 60–121% (35–108% and 94–128% for the protein-bound and free iodide, respectively), indicating the activation of the uptake and organification of iodide. The long-term injection of both low and high doses of potassium iodide increased the activity of catalase by 8–18% and SOD by 33–50% and enhanced the level of toxic LPO products reacting with thiobarbituric acid by 15–38%. It is suggested that reactive oxygen species and the excessive iodination of proteins (particularly thyroglobulin) induced by the long-term administration of high doses of potassium iodide can play an important role in the development of thyroid dysfunctions and autoimmune diseases.     

Thyroid Scanning with 131Cs

Scanning of the thyroid gland after the administration of radioactive caesium (¹³¹Cs) was performed in 45 patients; in 38 of these it had been shown that a thyroid nodule failed to accumulate sodium per-technetate (^99mTc) or sodum iodide (¹³¹I). ¹³¹Cs was concentrated in the nodule to a greater degree than in the paranodular thyroid tissue in seven patients, in five of whom thyroid carcinoma was subsequently identified. In five patients ¹³¹Cs accumulated in both the nodule and paranodular tissue, while in the other 26 no ¹³¹Cs uptake occurred in the nodule. In only one of the latter group was the thyroid lesion malignant. Caesium scanning seems to offer a useful supplementary procedure in the investigation of thyroid nodules.     

Potassium iodide (KI) to block the thyroid from exposure to I-131: current questions and answers to be discussed

Thyroid cancer in children and adolescents has to be considered as the most severe health consequence of a nuclear reactor emergency with release of radioiodine into the atmosphere. High doses of potassium iodide are effective to block radioiodine thyroid uptake and to prevent development of thyroid cancer years later. However, there are controversies concerning thyroid cancer risk induced by radioiodine exposure in adults. Further, the interaction of nutritional supply of potassium iodide and radioiodine uptake as well as the interaction of radioiodine with certain drugs has not been addressed properly in existing guidelines and recommendations. How to proceed in case of repeated release of radioiodine is an open, very important question which came up again recently during the Fukushima accident. Lastly, the side effects of iodine thyroid blocking and alternatives of this procedure have not been addressed systematically up to now in guidelines and recommendations. These questions can be answered as follows: in adults, the risk to develop thyroid cancer is negligible. In countries, where nutritional iodine deficiency is still an issue, the risk to develop thyroid cancer after a nuclear reactor emergency has to be considered higher because the thyroid takes up more radioiodine as in the replete condition. Similarly, in patients suffering from thyrotoxicosis, hypothyroidism or endemic goitre not being adequately treated radioiodine uptake is higher than in healthy people. In case of repeated or continued radioiodine release, more than one dose of potassium iodide may be necessary and be taken up to 1 week. Repeated iodine thyroid blocking obviously is not harmful. Side effects of iodine thyroid blocking should not be overestimated; there is little evidence for adverse effects in adults. Newborns and babies, however, may be more sensitive to side effects. In the rare case of iodine hypersensitivity, potassium perchlorate may be applied as an alternative to iodine for thyroid blocking.     

High bromide intake affects the accumulation of iodide in the rat thyroid and skin

The effect of a high bromide intake on the kinetics of iodide uptake and elimination in the thyroid and skin of adult male rats was studied. In rats fed a diet with sufficient iodine supply (>25 μg I/d), the iodide accumulation in the skin predominated during the first hours after ¹³¹I -iodide application. From this organ, radioiodide was gradually transferred into the thyroid. A high bromide intake (>150 mg Br⁻/d) in these animals led to a marked decrease in iodide accumulation, especially by the thyroid, because of an increase in iodide elimination both from the thyroid and from the skin. In rats kept under the conditions of iodine deficiency (<1 μ I/d), the iodide accumulation in the thyroid, but not in the skin, was markedly increased as a result of a thyrotropic stimulation. The effect of a high bromide intake (>100 mg Br⁻/d) in these animals was particularly pronounced because the rates of iodide elimination were most accelerated both from their thyroid and from their skin. Presented in part at the 20th Workshop on Macro and Trace Elements held in Jena (Germany) on December 1–2, 2000.     

From the molecular characterization of iodide transporters to the prevention of radioactive iodide exposure

In the event of a nuclear reactor accident, the major public health risk will likely result from the release and dispersion of volatile radio-iodines. Upon body exposure and food ingestion, these radio-iodines are concentrated in the thyroid, resulting in substantial thyroidal irradiation and accordingly causing thyroid cancers. Stable potassium iodide (KI) effectively blocks thyroid iodine uptake and is thus used in iodide prophylaxis for reactor accidents. The efficiency of KI is directly related to the physiological inhibition of the thyroid function in the presence of high plasma iodide concentrations. This regulation is called the Wolff-Chaikoff effect. However, to be fully effective, KI should be administered shortly before or immediately after radioiodine exposure. If KI is provided only several hours after exposure, it will elicit the opposite effect e.g. lead to an increase in the thyroid irradiation dose. To date, clear evaluation of the benefit and the potential toxicity of KI administration remain difficult, and additional data are needed. We outline in this review the molecular characterization of KI-induced regulation of the thyroid function. Significant advances in the knowledge of the iodide transport mechanisms and thyroid physiology have been made. Recently developed molecular tools should help clarify iodide metabolism and the Wolff-Chaikoff effect. The major goals are clarifying the factors which increase thyroid cancer risk after a reactor accident and improving the KI administration protocol. These will ultimately lead to the development of novel strategies to decrease thyroid irradiation after radio-iodine exposure.     

Intrathyroidal iodine metabolism in the rat. The influence of diet and the administration of thyroid-stimulating hormone

1. Ratios of mono[¹³¹I]iodotyrosine and di[¹³¹I]iodotyrosine (R values) and the incorporation of ¹³¹I into iodothyronines have been estimated in rat thyroid glands from 30min. to 38hr. after the administration of [¹³¹I]iodide. 2. In rats receiving a powdered low-iodine diet the R values were close to unity and did not change with time after the administration of [¹³¹I]iodide. In rats receiving a commercial pellet diet the R values fell from a mean of 0·8 at 30min. after [¹³¹I]iodide administration to 0·49 at 38hr. 3. Administration of 0·5–2·0i.u. of thyroid-stimulating hormone before giving the injection of [¹³¹I]iodide caused a small diminution in the R value when the time between injecting [¹³¹I]iodide and killing the animal was 16hr. or more. 4. Iodothyronines represented a greater percentage of the total thyroid-gland radioactivity in the iodine-deficient animals than in animals fed on the pellet diet. Thyroid-stimulating hormone had little effect, if any, on the iodothyronine contents.     

The effect of long-term external ionizing radiation on the functional activity of rat thyroid under enhanced potassium iodide consumption

The study was devoted to the effect of long-term (20 days) external ionizing radiation at a dose of 0.5 Gy on the iodide metabolism in the rat thyroid under supplementation of high iodine doses (10 daily KI doses). It was found that the potassium iodide administration partially prevented the effects of a post radiation decrease of serum thyroid hormone levels (the level of T4 was normal and that of T3 was 77.4% of the controls). After the supplementation of 10 daily iodide doses, the rat thyroid tissue showed the most pronounced increase in the levels of total, free and protein-bound iodide compared to the groups of animals consuming normal and elevated KI doses. Pronounced inhibition of thyroid peroxidase activity (3.1-fold) was noted in the same group. The data obtained indicate a radiation-induced activation of iodide uptake during its enhanced supplementation and disturbed iodide enzymatic oxidation and organification.     

Hipertiroidismo y captaciones de yodo bajas en una paciente con enfermedad de Graves

Thyrotoxicosis factitia is defined as thyrotoxicosis resulting from exogenous ingestion of thyroid hormone, usually in patients with a psychiatric disorder. Diagnosis can be difficult and this entity should be suspected in patients with high free tiroxine (T4) concentrations, low or suppressed thyroglobulin concentrations, normal urinary iodide excretion and low or suppressed ¹³¹I uptake. To establish the differential diagnosis, thyrotoxicosis factitia must be distinguished from several diseases with low ¹³¹I uptake, such as Graves’ disease, subacute thyroiditis, hyperthyroidism due to excessive iodine intake, struma ovarii and metastasis from thyroid cancer. Treatment is based on b-blockers to reduce symptoms and avoid iatrogeny. We present a case of thyrotoxicosis factitia treated in our outpatient clinic.     

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.     

Regulation of sodium iodide symporter gene expression by Rac1/p38β mitogen-activated protein kinase signaling pathway in MCF-7 breast cancer cells

Activation of p38 MAPK is a key pathway for cell proliferation and differentiation in breast cancer and thyroid cells. The sodium/iodide symporter (NIS) concentrates iodide in the thyroid and lactating breast. All-trans-retinoic acid (tRA) markedly induces NIS activity in some breast cancer cell lines and promotes uptake of β-emitting radioiodide (131)I sufficient for targeted cytotoxicity. To identify a signal transduction pathway that selectively stimulates NIS expression, we investigated regulation by the Rac1-p38 signaling pathway in MCF-7 breast cancer cells and compared it with regulation in FRTL-5 rat thyroid cells. Loss of function experiments with pharmacologic inhibitors and small interfering RNA, as well as RT-PCR analysis of p38 isoforms, demonstrated the requirement of Rac1, MAPK kinase 3B, and p38β for the full expression of NIS in MCF-7 cells. In contrast, p38α was critical for NIS expression in FRTL-5 cells. Treatment with tRA or overexpression of Rac1 induced the phosphorylation of p38 isoforms, including p38β. A dominant negative mutant of Rac1 abolished tRA-induced phosphorylation in MCF-7 cells. Overexpression of p38β or Rac1 significantly enhanced (1.9- and 3.9-fold, respectively), the tRA-stimulated NIS expression in MCF-7 cells. This study demonstrates differential regulation of NIS by distinct p38 isoforms in breast cancer cells and thyroid cells. Targeting isoform-selective activation of p38 may enhance NIS induction, resulting in higher efficacy of (131)I concentration and treatment of breast cancer.     

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。     

Seasonal characteristics of the effect of melatonin on thyroid function

Changes in pituitary-thyroid axis sensitivity to bioactive component of pineal gland, melatonin, have been detected. In winter (short days) melatonin (100 micrograms/100 g of rat body weight) decreased T3 T4, TSH content and 131I uptake by thyroid tissue. However, it was noted that in summer (long photoperiod) the same injection caused suppression of T3 plasma level and 131I uptake ability of the thyroid gland, with T4 and TSH blood levels remaining significantly increased.     

Thyroid cancer after diagnostic administration of iodine-131 in childhood.

Hahn, K., Schnell-Inderst, P., Grosche, B. and Holm, L-E. Thyroid Cancer after Diagnostic Administration of Iodine-131 in Childhood. Radiat. Res. 156, 61-70 (2001).To determine the carcinogenic effects of diagnostic amounts of (131)I on the juvenile thyroid gland, a multicenter retrospective cohort study was conducted on 4,973 subjects who either had been referred for diagnostic tests using uptake of (131)I (n = 2,262) or had had a diagnostic procedure on the thyroid without (131)I (n = 2,711) before the age of 18 years. Follow-up examinations were conducted after a mean period of 20 years after the first examination in 35% of the exposed subjects (n = 789) and in 41% of the nonexposed subjects (n = 1,118). Iodine-131 dosimetry of the thyroid was carried out according to ICRP Report No 53, and the median thyroid dose was 1.0 Gy. In the exposed group, two thyroid cancers were found during 16,500 person-years, compared to three cancers in the nonexposed group during 21,000 person-years. The relative risk for the exposed group was 0.86 (95% CI: 0.14-5.13). The study did not demonstrate an increased risk for thyroid cancer after administration of (131)I in childhood.     

Biokinetics of iodine-131 in rat thyroid following lead and lithium supplementation

The impact of lead as an environmental pollutant on the I-131 uptake and retention in rat thyroid was assayed alone and in combination with lithium treatment. Lead treatment significantly stimulated the 2- and 24-h uptake of I-131 in the thyroid, and the 24-h uptake showed the maximum stimulation after 3 mo of lead treatment. On the contrary, lithium supplementation reduced the uptake significantly and the maximum decrease was noticed after 2 mo of lithium administration. Further, simultaneous lead and lithium treatment resulted in more pronounced increase in the uptake of I-131 by the thyroid, which was maximum after 3 mo of combined treatment. The thyroidal biological half-life of I-131 (T _biol) was found to be increased significantly following lead and lithium treatments when given separately. Interestingly, combined lead and lithium treatment given up to 2 mo further prolonged theT _biol of I-131, thus reflecting its increased retention.     

Extensive scleral perforation with complete recovery

Sixty patients with abnormally high I(131) uptake were treated with liothyronine (L-triiodothyronine) for seven or eight days and then tested again. Fifty-five patients showed a suppression of iodine uptake sufficient to eliminate the possibility of hyperthyroidism. Also the therapeutic trial of liothyronine indicated whether they were euthyroid, or hypothyroid with iodine deficiency. Six of the patients showed insignificant change in the I(131) uptake after treatment with thyroid hormone-that is, the change from the original uptake was less than 30 per cent. These six patients were later confirmed to be hyperthyroid. In four patients the uptake at the second test was less by between 35 and 52 per cent than at the first. These four patients, like the remainder with even greater suppression in thyroid uptake, remained clinically euthyroid.The repeat I(131) uptake test was thus seen to be considerably more accurate than the single test and well worth the time required to perform it.