Effect of emodin on T cell subsets in NOD mice with NaI­induced experimental autoimmune thyroiditis.

Chronic lymphocytic thyroiditis (CLT), also known as Hashimoto's thyroiditis, is an autoimmune disease in which the thyroid gland is gradually destroyed. To date, only a limited number of agents can effectively suppress thyroiditis development in CLT patients. The aim of the current study was to investigate the protective effect of emodin on experimental autoimmune thyroiditis (EAT) in mice, which is considered an excellent model for CLT. NaI was used to induce the EAT model in non­obese diabetic (NOD) mice. An ELISA method was employed to detect the TgAb level (thyroid inflammation) in the serum of the EAT mice. The T cell subsets in peripheral blood and spleen were detected by flow cytometry. The histopathological study revealed that the thyroid inflammatory cell infiltration was significantly reduced by emodin compared with the model group. In addition, ELISA assays indicated that the NaI­induced serum TgAb upregulation was dramatically revered by emodin. Moreover, the level of serum IFN­Î³ and the cell populations of CD3+CD4+IL­4+, CD3+CD4+ IFN­Î³+, CD3+CD8+IL­4+, CD3+CD8+ IFN­Î³+ T cells in peripheral blood monocytes and splenic lymphocytes were significantly increased by NaI in the model group compared with in the normal group. Nevertheless, this type of increase was markedly attenuated by emodin. To conclude, the EAT model was successfully established by treating NOD mice with NaI. Emodin indicated an inhibitory effect on the autoimmune response that was significantly different in EAT compared with control mice. Furthermore, the anti­inflammatory action of emodin on EAT mice may be mediated via the inhibition of the secretion of IFN­Î³ and the cell numbers of CD3+CD4+IL­4+, CD3+CD4+ IFN­Î³+, CD3+CD8+IL­4+ and CD3+CD8+ IFN­Î³+ T cells in the peripheral blood monocytes and splenic lymphocytes. Therefore, the data may offer valuable insight on the efficacy of treatment of CLT with emodin.

Study of cytogenetic toxicity of low-dose radioiodine therapy in hyperthyroid patients using a micronuclei assay.

OBJECTIVE: Radioiodine, in low doses, has been used as a treatment modality for hyperthyroidism worldwide for a long time. However, there is little information available on the severity of cytotoxicity of radioiodine at these low doses. The present investigation aimed to study the cytogenetic toxicity of low-dose radioiodine in hyperthyroid patients using a cytokinesis-blocked micronuclei (MN) assay. MATERIALS AND METHODOLOGY: All of the patients received radioiodine in the form of sodium iodine (oral form). Blood samples of these patients were collected before therapy and 3 months after therapy, and lymphocytes were analysed for MN assay. RESULTS: Peripheral blood lymphocytes were analysed in 74 hyperthyroid patients (52 men, 22 women). The results indicated a positive relationship between age and the frequency of MN. However, there was no statistically significant difference in MN frequency at 3 months after therapy in comparison with that before therapy. CONCLUSION: This study showed that the cytogenetic damage produced by low-dose radioiodine was transient and reversible. Thus, patients can be motivated to undergo this safe and easy procedure as a modality of treatment for hyperthyroidism.

Evidence that MHC I-E dampens thyroid autoantibodies and prevents spreading to a second thyroid autoantigen in I-A(k) NOD mice.

NOD.H2(k) and NOD.H2(h4) mice carry the major histocompatibility complex (MHC) class II molecule I-A(k) associated with susceptibility to experimentally induced thyroiditis. Dietary iodine-enhanced spontaneous thyroid autoimmunity, well known in NOD.H2(h4) mice, has not been investigated in NOD.H2(k) mice. We compared NOD.H2(h4) and NOD.H2(k) strains for thyroiditis and autoantibodies to thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) without or with dietary sodium iodide (NaI) for up to 32 weeks. TgAb levels were significantly higher in NOD.H2(h4) compared with NOD.H2(k) mice on NaI, and TPOAb developed in NOD.H2(h4) mice but not in NOD.H2(k) mice. DNA exome analysis revealed, in addition to the differences in the chromosome (Chr) 17 MHC regions, that NOD.H2(k) mice, and particularly NOD.H2(h4) mice, have substantial non-MHC parental DNA. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis highlighted thyroid autoimmunity and immune-response genes on Chr 17 but not on Chr 7, and 15 parental B10.A4R DNA. Studies of parental strains provided no evidence for non-MHC gene contributions. The exon 10 Tg haplotype, associated with experimentally induced thyroiditis, is absent in NOD.H2(h4) and NOD.H2(k) mice and is not a marker for spontaneous murine thyroid autoimmunity. In conclusion, the absence of I-E is a likely explanation for the difference between NOD.H2(h4) and NOD.H2(k) mice in TgAb levels and, as in humans, autoantibody spreading to TPO.

Exposure levels associated with Na(131)I thyroid cancer patients: correlation with initial activity and clinical physical parameters.

Initial radiation exposure levels X (0) at 1 m from the navel of thyroid cancer patients were measured for 165 individuals at the time of ingestion. Some 61 patients had previously signed informed consent so only those patients could be assayed with regard to body parameters. While the activity was in the stomach, resultant X (0) values were seen to be linearly correlated with the total (131)I activity (A) given orally. Yet large differences in X (0) were seen; e.g., at A = 7.4 GBq, variations of a factor of four were found between the largest and smallest exposure rates. Correlation analyses were performed between normalized rate X (0)A-1 and several patient physical parameters. These included age, sex, height, weight, and BMI (body mass index). Only weight and BMI had significant linear correlation (p < 0.05) with normalized exposure rate. In the former case, the correlation coefficient ρ (weight) was -0.296 (p = 0.02). Using BMI as the independent variable, ρ (BMI) was -0.386 (p = 0.0021). With further analysis of the BMI variation, 95% confidence intervals could be determined at various BMI levels. For example, at 28 kg m(-2), the normalized rate varied between 0.039 and 0.0446 µGy h(-1) MBq(-1)-approximately a ±6.5% variation on the mean value of 0.0419 µGy h(-1) MBq(-1) at this BMI. Given such clinical information, differences in normalized exposure rate can be reduced to values on the order of ±10% or less for BMI values over the clinically relevant interval 20 to 40 kg m(-2).

A summary of the iodine supplementation study protocol (I2S2): a UK multicentre randomised controlled trial in preterm infants.

This paper summarises the study protocol for the randomised controlled trial of iodine supplementation in preterm infants. Iodine is essential for the synthesis of thyroxine, and thyroxine is essential for normal brain development in utero and for the first 2-3 years of life. The recommended iodine intake in parenteral nutrition regimens is 1 µg/kg/day and commercially available parenteral solutions for infants reflect these recommendations. In the absence of other iodine sources, infants are vulnerable to negative iodine balance and insufficiency. As many preterm infants are fed parenterally for prolonged periods with solutions which have been shown to be iodine-deficient, the I2S2 Trial was designed to establish whether iodine supplementation of preterm infants benefits neurodevelopment.

Prolonged high iodine intake is associated with inhibition of type 2 deiodinase activity in pituitary and elevation of serum thyrotropin levels.

Our previous epidemiological study indicated that excessive intake of iodine could potentially lead to hypothyroidism. In the present study, we aimed to investigate the time and dose effect of iodine intake on serum thyrotropin (thyroid-stimulating hormone, TSH) levels and to explore the non-autoimmune regulation of serum TSH by pituitary type 2 deiodinase (D2). A total of 360 Wistar rats were randomly divided into five groups depending on administered iodine dosages (folds of physiological dose): normal iodine (NI), 3-fold iodine (3HI), 6-fold iodine (6HI), 10-fold iodine (10HI) and 50-fold iodine (50HI). At 4, 8, 12 and 24 weeks after administration of sodium iodide, blood was collected for serum TSH measurement by chemiluminescent immunoassay. Pituitaries were also excised for measurement of TSHß subunit expression, D2 expression and activity, monocarboxylate transporter 8 (MCT8) and thyroid hormone receptor ß2 isoform (TRß2) levels. The results showed that iodine intake of 10HI and 50HI significantly increased pituitary and serum TSH levels from 8 to 24 weeks (P < 0·05 v. NI). Excess iodine had no effect on D2 mRNA or protein expression; however, 10HI and 50HI administration significantly inhibited pituitary D2 activities from 8 to 24 weeks (P < 0·05 v. NI). Iodine had no effect on MCT8 or TRß2 protein levels. We conclude that prolonged high iodine intake inhibits pituitary D2 activity and induces elevation of serum TSH levels. These findings may provide a potential mechanism of iodine excess-induced overt and subclinical hypothyroidism.

Evaluation of the p53 tumor suppressor gene mutation in normal rat salivary gland tissue after radioiodine application: an experimental study.

In this experimental study, investigators explored p53 tumor suppressor gene mutation induced by low and high doses of iodine-131 sodium iodide (I-131) in salivary gland tissue in rats. Group 1 consisted of 10 rats; low and high I-131 doses were applied at a 1-wk interval. First,low doses of I-131 were injected. (The net injected dose was 47.5-/+9.2 microCi.) After 1 wk, high doses of I-131 were also injected. (The net injected dose was 1007.2-/+53 microCi.) Group 2 consisted of 5 rats, and only a low I-131 dose was applied. (The net injected dose was 52.7-/+5.5 microCi.) The Control Group consisted of 5 rats that did not receive I-131. Thyroidal I-131 uptakes were calculated for Groups 1 and 2 with the use of a gamma camera after 24 h of injections. Immediately after uptake was calculated, salivary glands were resected in all groups and DNA was extracted for genotyping. Genomic DNA of the p53 gene exon 5 was examined by polymerase chain reaction single-strand conformational polymorphism. In Group 1, thyroidal I-131 uptakes were calculated as 12.45%-/+4.14% and 9.66%-/+6.73% after low-dose and high-dose I-131 applications, respectively. In Group 2, thyroidal I-131 uptake was calculated as 13.12%-/+3.04%. In Group 1, p53 gene abnormality was seen in the salivary gland of only 1 of the rats. Double- and single-strand gene profiles showed that both alleles of this rat have a mutated single-strand conformational polymorphism profile of point mutation in the p53 gene exon 5. This rat received the highest low dose and the second highest total dose of I-131; its thyroidal uptakes were the second highest. In the other rats in Group 1, and in Group 2 and the Control Group, p53 gene abnormalities were not observed. In Groups 1 and 2, a significant relationship could not be discerned between thyroidal uptake of I-131 and p53 gene mutation in the salivary gland. No significant relationship was observed between thyroidal uptake alterations and p53 gene mutations in salivary glands in Group 1. A point mutation in the p53 gene exon 5 that was seen in only 1 of the rats in Group 1 seems related to the high-dose application of I-131, although coincidental occurrences could not be excluded. We believe that this topic is open to additional in vivo studies.

Amiodarone compared with iodine exhibits a potent and persistent inhibitory effect on TSH-stimulated cAMP production in vitro: a possible mechanism to explain amiodarone-induced hypothyroidism.

Amiodarone (AMD) is a powerful anti-arrhythmic drug used for the treatment of a wide variety of cardiac arrhythmias and its most striking feature is its high iodine content. Thyroid dysfunction is a limiting side-effect of the drug and both AMD-induced hypothyroidism (AIH) and AMD-induced thyrotoxicosis (AIT) are reported. To examine the hypothesis that altered bioavailability of iodine is a contributing event in the pathogenesis of AIH, we compared the effects of AMD and inorganic iodine in vitro on events involved in the process of thyroid autoregulation. FRTL-5 cells and JP26 CHO cells (transfected with the human TSH receptor) were exposed to AMD or NaI in the presence of TSH, and cAMP production was measured as an indicator of cellular function. Forskolin and cholera toxin were also used to determine the possible target sites of AMD and iodide. Our results indicated that there was a difference between the effects of AMD versus those of physiological doses of iodide. The inhibitory effects of AMD occurred at lower concentrations of iodide than those seen in the NaI-treated cells. The effects of AMD were irreversible indicating a possible persistence of the Wolff-Chaikoff effect due to a constant high intracellular iodide level. The inhibitory effects of AMD (also seen at supraphysiological doses of iodide) were partially overcome by forskolin but not by cholera toxin indicating an effect on TSH receptor interactions with the other signal transduction elements such as G proteins and adenylate cyclase. The persistence of the Wolff-Chaikoff effect through loss of autoregulation may be a mechanism of the observed hypothyroidism in some patients taking AMD. The combined effects of the constant release of iodide together with the drug toxicity may be the mechanism for the observed effects.

[Use of iodized salt and the risk of iodine overload]. / Utilisation du sel iodé et risque de surcharge en iode.

Iodine-deficiency disorders are a major problem of public health in Morocco. To mitigate this deficiency, the iodination of all the salt intended for human consumption in a proportion of 80 +/- 10 mg/kg of salt has become obligatory since a decree published in 1995. We estimated that this rate of iodized salt issued risked inducing an iodine excess in the population. To check this hypothesis, we provided 7 families made up of 28 subjects, who at the start were consuming a non-iodized salt, with the decreed, iodized salt and we followed the evolution of their urinary iodine excretion over a period of 3 weeks. The mean values of urinary iodine excretion of the 28 subjects were 12.8 micrograms/dl before use of iodized salt and 26.8, 35.5 and 63.2 micrograms/dl, respectively, after 7, 14 and 21 days from the introduction of iodized salt into their diet. After 21 days of the use of iodized salt, 84.6 per cent of the subjects had an iodine excess. We conclude that prolonged use of this iodized salt exposes the population to the risk of thyroid disorders.

Iodine replacement in fibrocystic disease of the breast.

OBJECTIVE: To determine the response of patients with fibrocystic breast disease to iodine replacement therapy. DESIGN: Review of three clinical studies beginning in 1975: an uncontrolled study with sodium iodide and protein-bound iodide; a prospective, control, crossover study from iodide to molecular iodine; and a prospective, control, double-blind study with molecular iodine. SETTING: University affiliated breast-treatment clinics. PATIENTS: Study 1: 233 volunteers received sodium iodide for 2 years and 588 received protein-bound iodide for 5 years. Study 2: the treatment of 145 patients from study 1 treated with protein-bound iodide for several months who still had symptoms was switched to molecular iodine 0.08 mg/kg; 108 volunteers were treated initially with molecular iodine. Study 3: 23 patients received molecular iodine, 0.07 to 0.09 mg/kg body weight; 33 received an aqueous mixture of brown vegetable dye and quinine. The numbers in study 2 increased over the review period so that 1365 volunteers were being treated with molecular iodine by 1989. INTERVENTIONS: All patients in study 3 had pre- and post-treatment mammography and measurement of serum triiodothyronine, thyroxine and thyroid-stimulating hormone levels. MAIN OUTCOME MEASURES: Subjective evaluation--freedom from pain--and objective evaluation--resolution of fibrosis. RESULTS: Study 1: 70% of subjects treated with sodium iodide had clinical improvement in their breast disease, but the rate of side effects was high; 40% of patients treated with protein-bound iodide had clinical improvement. Study 2: 74% of patients in the crossover series had clinical improvement, and objective improvement was noted in 72% of those who received molecular iodine initially. Study 3: in the treatment group 65% had subjective and objective improvement; in the control group there was a subjective placebo effect in 33% and an objective deterioration of 3%. CONCLUSIONS: The fibrocystic breast reacts differently to sodium iodide, protein-bound iodide and molecular iodine. Molecular iodine is nonthyrotropic and was the most beneficial.

[Tuberous iododerma from solutan]. / Tuberoznaia iododerma ot solutana.

The literature data on this condition are reviewed and a 22-year-old female patient with solutan-induced tuberous iododerma is described.

Five patients with iodine-induced hyperthyroidism.

Iodine-induced hyperthyroidism has been frequently described when iodine is introduced into an iodine-deficient area. However, it may also occur in patients with and without previous thyroid disease residing in iodine-sufficient areas. Five patients with iodine-induced hyperthyroidism seen in a 12-month period are described. All were exposed to iodine in the form of commonly used drugs (Betadine, Iodo-Niacin, amiodarone, and radiographic contrast dyes). The cause of iodine-induced hyperthyroidism is unclear, but it is probably more common in patients with goiters containing previously existing areas of autonomous function or iodine-poor thyroglobulin. Iodine-induced hyperthyroidism usually abates after iodine withdrawal in patients with multinodular goiters or normal thyroid glands. The hyperthyroidism is usually treated with beta-blockers and antithyroid thionamide drugs, although reinstitution of iodine to block thyroid hormone release or corticosteroids occasionally may be necessary. Iodine-containing drugs should be given with caution to patients with underlying thyroid disease.

Jodbasedow and thyrotoxic periodic paralysis.

A 37-year-old white man with a multinodular goiter had thyrotoxicosis develop after iodine administration (Jodbasedow). His hyperthyroid state was accompanied by thyrotoxic periodic paralysis, a complication of hyperthyroidism that is usually seen in Orientals. The patient manifested typical features of each disorder. As classically described, these two thyroid-related disorders should rarely coexist because of epidemiologic considerations; however, the population at risk may be greater than has generally been appreciated.