Induced Thyroid Dysfunction Research Articles

Iodide-Induced Chemokines and Genes Related to Immunological Function in Cultured Human Thyroid Follicles in the Presence of Thyrotropin

It is well known that iodide exacerbates thyroid function in subclinical hypothyroid patients with autoimmune thyroiditis. To investigate the immunological mechanism of iodine-induced thyroid dysfunction, we studied the effect of iodide in cultured human thyroid follicles, which respond to physiological concentrations of human thyrotropin (TSH) (0.3-10 microU/mL) and maintain the Wolff-Chaikoff effect. Thyroid follicles obtained from Graves' patients at subtotal thyroidectomy were precultured in medium containing 0.5% fetal calf serum and 10(-8) M iodide for 5 days, and then cultured with the medium containing bovine TSH (30 microU/mL) and low (10(-8)M) or high (10(-5)M) concentrations of iodide. After 3-72 hours of culture, the effect of iodide on thyroid cell mRNA expression was analyzed by microarray and reverse transcriptase-polymerase chain reaction. After 48 hours of culture, iodide nearly doubled the mRNA expression levels of the immunity-associated genes (intercellular adhesion molecule-1, transforming growth factor beta 1-induced protein, early growth response gene 1, guanylate-binding protein 1, and annexin A1) and decreased the mRNA expression of sodium-iodide symporter to less than 20%. Further, the mRNA expression levels of chemokines (CCL2, CXCL8, and CXCL14) increased nearly twofold, whereas their receptors did not show any significant response. Real-time polymerase chain reaction analyses confirmed that iodide increased the mRNA expression levels of these genes in a time- and concentration-dependent manner. Immunohistochemical studies revealed that the chemokines were expressed mainly in the thyroid follicular cells in addition to the immune cells. The iodide-induced increase in CCL2 was greater in thyroid follicles obtained from thyroid gland that had been moderately infiltrated with the immunocompetent cells. We have demonstrated that iodide stimulates thyroid follicular cells to produce chemokines, particularly CCL2, CXCL8, and CXCL14. These chemokines and intercellular adhesion molecule-1 would attract immunocompetent cells into thyroid gland. These in vitro findings suggest that iodide at high concentrations may induce thyroid dysfunction through not only biochemical but also immunological mechanisms, particularly in patients with autoimmune thyroid disorders.

Sunitinib-Induced Thyrotoxicosis Followed by Persistent Hypothyroidism with Shrinkage of Thyroid Volume

Sunitinib, a tyrosine kinase inhibitor, has been approved for the treatment of cancers, such as advanced renal cell carcinoma (RCC). On the other hand, sunitinib treatment is known to induce thyroid dysfunction in a substantial proportion of patients treated for advanced RCC; in fact, hypothyroidism is a frequent complication. However, little is known about sunitinib-induced thyrotoxicosis and destructive thyroiditis. Here, we report a patient with RCC who developed transient overt thyrotoxicosis followed by hypothyroidism due to sunitinib treatment. A 58-year-old woman, who had been treated with chronic thyroiditis, was diagnosed as having left RCC with bone metastasis to the rib. The patient underwent resection of the left kidney and the bone metastasis lesion. However, 3 months later, bone metastasis to the rib recurred, and sunitinib treatment was started. At 6 weeks of sunitinib therapy, the patient developed transient thyrotoxicosis, followed by persistent hypothyroidism. In the thyrotoxic phase, the patient was diagnosed as having destructive thyroiditis based on an increased thyroglobulin level, a low radioactive iodine uptake, increased free thyroxine level, and suppressed thyroid-stimulating hormone level. The thyroid volume in the hypothyroid phase was 68% of that in the thyrotoxic phase. In conclusion, the present report suggests that sunitinib-induced persistent hypothyroidism may be a consequence of preceding destructive thyroiditis with transient thyrotoxicosis. The decreased volume of the thyroid during the hypothyroid phase indicates irreversible organ damage in the present patient, thereby resulting in persistent hypothyroidism. Thus, periodic surveillance of thyroid function is mandatory during sunitinib therapy.

Effects of combined interferon alpha and ribavirin therapy on thyroid functions in patients with chronic hepatitis C.

To determine the frequency of thyroid dysfunction in patients of chronic hepatitis C during treatment with interferon alpha-2b and ribavirin therapy. A cohort study. Army Medical College and Military Hospital, Rawalpindi, from February 2006 to January 2007. One hundred and sixty seven non-cirrhotic chronic hepatitis C patients were grouped into treatment group (n=107) and control group (n=60) awaiting treatment. Baseline serum(s.) Alanine Transferase (ALT) and S. Aspartate Transferase (AST) were measured by IFCC method. Serum Thyroid Stimulating Hormone (S. TSH), serum free thyroxine (S. Free T4) and serum total triiodothyronine (S.T3) level were determined by chemiluminescence. Study group patients underwent 24 weeks IFN and ribavirin therapy and were followed-up for thyroid dysfunction at weeks 0, 12 and 24. Control group patients underwent the same tests at weeks 0, 12 and 24. Statistical analysis was done on SPSS 15. Out of 107 patients of treatment group, 20 patients (18.69%) developed thyroid dysfunction. Females were at higher risk with Relative Risk (RR) of 11.25 and Attributable Risk (AR) of 91%. Hypothyroidism was more common than hyperthyroidism. Interferon-alpha and ribavirin therapy induces thyroid dysfunction in chronic hepatitis C patients. Hypothyroidism was more common. Females are at a higher risk of developing thyroid dysfunction.

Fluoride-induced thyroid dysfunction in rats: roles of dietary protein and calcium level

To assess the roles of dietary protein (Pr) and calcium (Ca) level associated with excessive fluoride (F) intake and the impact of dietary Pr, Ca, and F on thyroid function, 144 30-day-old Wistar albino rats were randomly allotted to six groups of 24 (female:male = 1:1). The six groups were fed (1) a normal control (NC) diet (17.92% Pr, 0.85% Ca = NC group); (2) the NC diet and high F (338 mg NaF [=150 mg F ion]/L in their drinking water = NC+F group); (3) low Pr and low Ca diet (10.01% Pr, 0.24% Ca = LPrLCa group); (4) low Pr and low Ca diet plus high F = LPrLCa+F group; (5) high Pr and low Ca diet plus high F (25.52% Pr, 0.25% Ca = HPrLCa+F group); and (6) low Pr and high Ca diet plus high F (10.60% Pr, 1.93% Ca = LPrHCa+F group). The areas of thyroid follicles were determined by Image-Proplus 5.1, and triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 (FT4) levels in serum were measured by radioimmunoassay. The histopathological study revealed obviously flatted follicular epithelia cells and hyperplastic nodules, consisting of thyroid parafollicular cells that appeared by excessive F ingestion, on the 120th day. Pr or Ca supplementation reverses the F-induced damage in malnutrition. The serum T3, FT3, T4, and FT4 levels in the NC+F group were significantly decreased and significantly increased in the LPrLCa+F group. Thus, excessive F administration induces thyroid dysfunction in rats; dietary Pr and Ca level play key roles in F-induced thyroid dysfunction.

A Case of Lithium-Associated Painless Thyroiditis

Lithium, prescribed for bipolar disorder, is known to induce thyroid dysfunction, most commonly hypothyroidism. Thyrotoxicosis due to lithium-induced painless thyroiditis is a rare complication. We have previously reported that the serum concentration of immunosuppressive acidic protein (IAP), an α1-acid glycoprotein, increased during the acute phase of subacute thyroiditis, but was within the normal range in patients with painless thyroiditis. In the present case, a 31-year-old woman, receiving long-term lithium therapy for bipolar disorder, had a recurrent episode of painless thyroiditis, and her serum IAP was increased. The pathogenic mechanism for lithium-associated painless thyroiditis may differ from that of autoimmune conditions.

Reversal of Cadmium-Induced Thyroid Dysfunction by Selenium, Zinc, or Their Combination in Rat

The aim of this study was to evaluate the potential benefit of combined treatment with zinc (Zn) and selenium (Se) in reversing cadmium (Cd)-induced thyroid dysfunction compared to Se or Zn treatment alone in rats exposed to Cd. For this purpose, 30 adult male Wistar albino rats were equally divided into control and four treated groups receiving either 200 ppm Cd (as CdCl2), 200 ppm Cd + 500 ppm Zn (as ZnCl2), 200 ppm Cd + 0.1 ppm Se (as Na2SeO3), or 200 ppm Cd + 500 ppm Zn + 0.1 ppm Se in their drinking water for 35 days. The results showed that Cd exposure increased significantly the relative thyroid weight (RTW), the thyroid Cd concentration, and the serum thyroid stimulating hormone (TSH) level, whereas the serum thyroxine (T4) level was decreased compared to control rats. The treatment of Cd-exposed rats with Se alone only partially protected from the Cd-induced decrease in serum T4 level. The treatment of Cd-exposed animals with Zn alone partially protected against Cd-induced thyroid dysfunction by maintaining normal RTW and by decreasing Cd concentration in the thyroid. It also partially prevents Cd-induced decrease in serum T4 level. The combined treatment of Cd-exposed animals with Se and Zn induced a more significant decrease in the thyroid Cd concentration than the Zn supplement and a total correction of the RTW. This treatment was also more effective than that with Se or Zn alone in reversing Cd-induced decrease in serum T4 level and Cd-induced increase in serum TSH level. Se and Zn can have a synergistic role against Cd-induced thyroid dysfunction.

Thyroid dysfunction in patients (pts) with metastatic renal cell cancer (RCC) treated with sorafenib

16145 Background: Sorafenib is an oral multi-target tyrosine kinase inhibitor (TKI) approved for the treatment of metastatic RCC. A high incidence of thyroid dysfunction has been observed with sunitinib, another TKI with overlapping mechanism of action. We evaluated prospectively the incidence and severity of thyroid function abnormalities in pts with metastatic RCC treated with sorafenib. Methods: A total of 46 patients received sorafenib for metastatic RCC and 38 patients were eligible for our single-centre prospective observational study. Sorafenib was administered continuously at a dose of 400 mg orally twice daily. Thyroid function (TSH, free thyroxine index) was assessed at baseline and on day 1 of each treatment cycle. Results: Of the 23 patients with normal baseline thyroid function, 7 patients (30%) developed at least one elevated serum TSH and one patient (5%) developed low TSH without requiring therapy. Fifteen patients (65%) did not develop any TFT abnormality. In the group of 15 pts with thyroid dysfunction at baseline or previous treatment potentially interfering with thyroid function 2 pts with baseline subclinical hypothyroidism developed clinical hypothyroidism during sorafenib treatment requiring hormone replacement. Two other pts developed drug-induced thyroiditis under sorafenib, however following radiotherapy of the cervical spine due to bone metastasis. In one patient under substitution therapy no change in substitution dose was needed during the course of sorafenib treatment. In seven patients with prior sunitinib treatment only one patient developed at least one elevated serum TSH, however not requiring therapeutic intervention. Conclusions: Sorafenib induces thyroid dysfunction and the risk seems to be higher in patients with pre-existing thyroid function test abnormalities and/or radiotherapy to the neck. In our hands the incidence of thyroid dysfunction is lower than with sunitinib, nevertheless pts with underlying thyroid disease may develop overt hypo- or hyperthyroidism requiring treatment. Therefore screening of thyroid function is also warranted in pts treated with sorafenib, at baseline and repeatedly during the treatment, especially in those with underlying thyroid disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Pfizer Bayer, Pfizer Bayer, Pfizer

Thyroid dysfunction in hepatitis C individuals treated with interferon-alpha and ribavirin: a review

Hepatitis C (HCV) is now the main cause of chronic hepatic disease, cirrhosis and hepatocellular carcinoma. Several extrahepatic diseases have been associated with chronic HCV infection, and in most cases appear to be directly related to the viral infection. Thyroid disorders are common in patients with chronic HCV. Some patients with chronic hepatitis C experience thyroid problems, and thyroid dysfunction may also be a side effect of interferon-based treatment. The principal risk factor for developing thyroid disease in the course of antiviral therapy is the previous positivity for anti-thyroid antibodies (anti-thyroid peroxidase) especially in older women. Screening for autoantibodies and serum thyroid-stimulating hormone is recommended before, during and after interferon-alpha treatment, and patients should be informed of the risk of thyroid dysfunction. This review includes a summary of thyroid disease associated with chronic HCV infection, interferon-alpha and ribavirin for treatment of HCV and potential to induce thyroid dysfunction.

Effect of excessive iodine exposure on the placental deiodinase activities andHoxc8expression during mouse embryogenesis

Excessive iodine induces thyroid dysfunction. However, the effect of excessive iodine exposure on maternal-fetal thyroid hormone metabolism and on the expression of genes involved in differentiation, growth and development is poorly understood. Since a thyroid hormone receptor response element was found in the Hoxc8 promoter region, Hoxc8 expression possibly regulated by excessive iodine exposure was firstly investigated. In the present study, Balb/C mice were given different doses of iodine in the form of potassium iodate (KIO3) at the levels of 0 (sterile water), 1.5, 3.0, 6.0, 12.0 and 24.0 microg/ml in drinking water for 4 months, then were mated. On 12.5 d postcoitum, placental type 2 and type 3 deiodinase activities and fetal Hoxc8 expression were determined. The results showed that excessive iodine exposure above 1.5 microg/ml resulted in an increase of total thyroxine and a decrease of total triiodothyronine in the serum of maternal mice, which was mainly associated with the inhibition of type 1 deiodinase activity in liver and kidney. Placental type 2 deiodinase activity decreased, showing an inverse relationship with maternal thyroxine level. Hoxc8 mRNA and protein expression at 12.5 d postcoitum embryos were down regulated. Because Hoxc8 plays an important role in normal skeletal development, this finding provides a possible explanation for the skeletal malformation induced by excessive iodine exposure and also provides a new clue to study the relationship between iodine or thyroid hormones and Hox gene expression pattern.

Thyroid Function after Coronary Angiography and Angioplasty

The issue of this study was the investigation of the frequency of the thyroid functional disorders after administration of the iodine-containing contrast media in patients located in iodine deficient region. 146 patients were examined, before and after the coronary angiography. Initially, the high frequency of the thyroid pathology was discovered (39%). The thyroid functional state and the urinary iodine excretion were estimated before and 1, 3, 6 and 12 months after the study. During 1 month after the coronary angiography several cases of thyrotoxicosis and hypothyroidism relapse were fixed, and also the deterioration of the course of the already present thyroid functional disorders was registered. The patients with the initial pathology and the thyroid functional disorders should be included into the risk group by the development of the iodine induced thyroid dysfunction.

Cardio-protective role of terazosin is possibly mediated through alteration in thyroid function

An investigation was made to reveal the possible involvement of thyroid hormones, if any, in terazosin (an alfa-1 adrenergic receptor blocker) induced alterations in tissue lipid peroxidation (LPO) and in the concentration of different serum lipids. We determined the impact of terazosin on the changes in hypercholesterolemic (CCT) diet induced thyroid dysfunction; cardiac, renal and hepatic LPO and on serum glucose concentration in female Wister rats. Simultaneously levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), creatinine, alkaline phosphatase (ALP) activity, hepatic glycogen synthesis and total daily food consumption were studied as supporting parameters. While a decrease in the level of serum thyroid hormones, HDL-C and in hepatic glycogen content, was observed in CCT diet fed animals; it increased the concentration of other serum lipids, glucose and creatinine; ALP activity; tissue and serum LPO. However, following terazosin administration for 15 days to CCT diet fed animals, status of thyroid hormones and all other thyroid dependent parameters were reversed suggesting that the drug might be acting through an alteration in the thyroid functions.

Sunitinib-related thyroid dysfunction: A single-center retrospective and prospective evaluation

3092 Background: Sunitinib is a multi-target tyrosine kinase inhibitor with anti-angiogenic and anti-proliferative activity mediated by signal blockade of VEGFR1/2, KIT, PDGFRα/β, and FLT-3. Phase II/III trials have demonstrated efficacy of the oral agent in Imatinib-resistant GIST and advanced renal cell cancer (RCC). We observed several cases of thyroid dysfunction in GIST during treatment with sunitinib suggesting that the drug may be associated with hypothyroidism. We therefore assessed the incidence and severity of thyroid dysfunction in cancer patients treated with sunitinib. Methods: Thyroid function (serum TSH, T3 and free thyroxin index) and thyroid antibodies (anti-TPO, -Tg and TSH-R-Ab) were evaluated retrospectively in a cohort of patients with GIST in a Phase III trial and in an expanded access program (1st part of the investigation) and in a prospective cohort of RCC and GIST patients treated in the framework of expanded access programs (2nd part). Sunitinib was given at a daily oral dose of 50 mg 4 weeks on, 2 weeks off. Thyroid parameters were assessed on days 1 and 28 of each treatment cycle in the prospective cohort. We report here the first TSH results, the full data set will be available at ASCO. Results: We identified a total of 46 patients who received sunitinib, and 33 of these patients were evaluable for thyroid function. 14 patients were analyzed retrospectively (all GIST), 19 patients prospectively (8 GIST, 11 RCC). 7 of these 19 patients (37%) showed an elevated TSH (>5 mIU/L) during treatment. In the retrospective analysis of 14 patients with a median treatment duration of 44 weeks, 8 patients (57%) had developed hypothyroidism. All patients with GIST in randomized Phase III trial remaining under active treatment with sunitinib for 58–80 weeks show an increased TSH (up to 83 mIU/L) during the course of treatment, requiring hormone substitution. In a cohort of 11 patients with RCC, after 6 weeks of treatment, 3 patients already have an increased TSH. Conclusions: Sunitinib is associated with a high incidence of thyroid dysfunction which requires further study. The mechanism by which Sunitinib induces thyroid dysfunction is yet unclear. No significant financial relationships to disclose.

Developmental toxic effects of chronic exposure to high doses of iodine in the mouse

Chronic exposure to high doses of iodine induces thyroid dysfunction, but effects of chronic exposure to high amounts of iodine on pregnancy and fetal outcome are uncertain. In the present study, Balb/C mice were given different doses of iodine at the levels of 0 (sterile water), 1500, 3000, 6000, 12,000 and 24,000 μg/L in drinking water for 4 months, then were mated and the developmental toxicity and teratogenicity were evaluated. An obvious colloid goiter was observed, and serum total thyroxine (TT 4) levels increased and serum total triiodothyronine (TT 3) levels decreased significantly in dams when iodine dose reached 3000 μg/L. Maternal effect was evident by the reduction of average daily food consumption in higher doses of iodine groups. Embryotoxicity and teratogenicity were mainly indicated by the reduced body weight in female fetuses, the decreased number of live fetuses, and the increased incidence of resorptions, and especially skeletal variations. These results suggest that exposure to maternally toxic doses of iodine may have a potential developmental toxic effect.

Thyroid hormone-dependent development of mouse cerebellar Purkinje cells in vitro

Using a well-defined medium with insulin, transferrin and selenium but without serum and albumin, we quantitatively determined the effect of thyroid hormones on the development of Purkinje cells in mouse cerebellar monolayer cultures. Addition of a thyroid hormone, T3 or T4, to the serum-free medium resulted in a highly elaborate dendritic development of Purkinje cells. The cultured Purkinje cells in the presence of T4 even showed similarities in shape and in synapse formation to normal Purkinje cells in vivo. Such effect of T4 on the dendritic arborization of Purkinje cells was dose dependent and significantly sensitive to a low dose of T4 even at 50 pM. The effect of T4 was confirmed by an inhibition experiment using amiodarone, which was reported to induce thyroid dysfunction. Furthermore, T4 affected not only Purkinje cell development but also the shape of other neural cells such as small interneurons (mainly granule cells) and astrocytes in cerebellar cultures. T4 induced development of both interneurons and astrocytes having long processes. These results indicate that thyroid hormones play a pivotal role in the development of mouse Purkinje cell dendrites acting on Purkinje cells directly and/or indirectly via the close interaction with interneurons and astrocytes.

Virologic factors related to interferon-alpha-induced thyroid dysfunction in patients with chronic hepatitis C.

Hepatitis C virus (HCV), being reported to be associated with a high prevalence of serological markers of autoimmunity in HCV-infected patients, and possibly sharing partial sequences in amino acid segments with thyroid tissue antigens, may be associated with interferon-alpha (IFN-alpha)-induced thyroid dysfunction in chronic hepatitis C patients. We conducted this study to clarify the issue. One hundred and fifty chronic hepatitis C patients with normal baseline thyroid function were treated with IFN-alpha 2a, 2b and n1 (3-6 million Units three times weekly for 24 weeks). Pretreatment sera were tested for HCV genotype and HCV RNA levels. Serum thyrotropin, total thyroxine and free thyroxine index were performed every 4 weeks for 24 weeks followed by every 8 weeks for another 24 weeks. Twenty-one (14.0%) patients developed early thyroid dysfunction (abnormal thyroid function during the first 3 months of therapy). Female gender, lower HCV RNA levels, IFN-alpha n1 and a lower IFN-alpha dose were significantly associated with early thyroid dysfunction. On multivariate analysis, gender, IFN-alpha preparation and HCV RNA levels were the significant factors associated with early thyroid dysfunction. Seven (4.7%) patients developed thyroid dysfunction during the second 3 months of IFN-alpha therapy. Taken together, 18.7% patients developed thyroid dysfunction. Female, mixed HCV genotype infection and lower HCV RNA levels were significantly associated with thyroid dysfunction. However, only gender remained significantly associated with IFN-alpha-induced thyroid dysfunction in multivariate analysis. The virologic features of HCV may be associated with thyroid dysfunction in chronic hepatitis C patients treated with IFN-alpha. Nevertheless, gender still plays the most important role in IFN-alpha-induced thyroid dysfunction.

Cadmium induced thyroid dysfunction in chicken: hepatic type I iodothyronine 5′-monodeiodinase activity and role of lipid peroxidation

Administration of cadmium chloride (2.5 mg/kg body weight/day) to chickens daily for 15 days decreased serum triiodothyronine (T 3) concentration (by 68.75%) without altering the levels of serum thyroxine (T 4). Hepatic 5′-monodeiodinase (5′D-I) and superoxide dismutase (SOD) activities were also decreased (by 90.47% and 20.81% respectively) with a concomitant increase in lipid peroxidation (LPO, by 206.25%). Administration of the antioxidant vitamin E (α-tocopherol, 5 mg/kg body weight on alternate days) to cadmium intoxicated chickens restored thyroid function by maintaining normal hepatic 5′D-I activity and serum thyroid hormone concentrations. It also prevented cadmium-induced increase in LPO. We conclude that the metal-induced inhibition in hepatic 5′D-I activity is mediated through LPO.

Role of ascorbic acid in cadmium-induced thyroid dysfunction and lipid peroxidation.

A study on the effects of ascorbic acid (AA) on heavy metal (cadmium)-induced thyroid dysfunction and lipid peroxidation (LPO) was carried out in Swiss male mice. The animals were administered with either cadmium (1.0 mg kg(-1) body wt.) alone or in combination with AA (1 mM) every day for 15 days. While cadmium treatment led to a decrease in the serum concentrations of thyroid hormones and hepatic type I iodothyronine 5'-monodeiodinase (5'D-I) activity, an increase in the level of lipid peroxidation was observed. The metal-induced decrease in hepatic 5'D-I activity and serum triiodothyronine (T3) concentration was restored by treatment with AA. However, AA could not restore the serum thyroxine (T4) concentration. The increased level of LPO was also ameliorated by AA. It appears that the protective effect of AA against cadmium-induced thyroid dysfunction is mediated through its antioxidative action.

Is triiodothyronine capable of ameliorating pyrethroid-induced thyroid dysfunction and lipid peroxidation?

A study on the effect of triiodothyronine (T3) in the regulation of pyrethroid (fenvalerate)-induced thyroid dysfunction and lipid peroxidation was carried out in male mice. Fenvalerate (120 mg kg(-1) body wt. daily for 15 days) administration led to a decrease in the serum concentration of thyroid hormones and the activity of hepatic type I iodothyronine 5'-monodeiodinase (5'D-I) and an increase in the level of lipid peroxidation. The decrease in the activity of hepatic 5'D-I due to the administration of fenvalerate was restored with the administration of T3 (7 microg kg[-1] body wt. on alternate days). The increased level of lipid peroxidation was also ameliorated by T3. However, T3 could not restore the serum concentration of thyroxine (T4), only that of T3. We suggest that the ameliorating role of T3 in the fenvalerate-intoxicated mice could be the result of the lipogenic action of the thyroid hormone, which in turn led to the restoration of 5'D-I activity.

Protective effects of vitamin E against lead-induced deterioration of membrane associated type-I iodothyronine 5′-monodeiodinase (5′D-I) activity in male mice

The protective role of vitamin E (vit E) on lead-induced thyroid dysfunction with special reference to type-I iodothyronine 5′-monodeiodinase (5′D-I) activity in mice liver was investigated. Daily intraperitoneal (i.p.) injection of lead acetate (0.5 mg/kg body weight) for 30 days significantly decreased serum 3,3′,5-triiodothyronine (T 3) concentration and hepatic 5′D-I activity. Furthermore, lead significantly increased peroxidative reactions involving membrane components (lipid peroxidation, LPO) while the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) were decreased in mouse liver. Simultaneous administration of vit E (5 mg/kg body weight) and 0.5 mg/kg body weight of lead restored thyroid function in mice by maintaining normal hepatic 5′D-I activity and serum thyroid hormone concentrations. It also prevented increase in LPO and inhibition of SOD and CAT activities in liver. We suggest that the intact membrane structure is a must for 5′D-I activity and the administration of vit E may prevent the lead induced thyroid dysfunction by maintaining membrane architecture.

Effects of excess iodine administration on thyroid function in euthyroid patients with a previous episode of thyroid dysfunction induced by interferon-alpha treatment.

To determine the effects of pharmacological quantities of iodide (SSKI) on thyroid function in euthyroid patients previously treated with recombinant interferon-alpha (rIFN-alpha) for chronic viral hepatitis B and C (HCV), a cytokine which may induce thyroid dysfunction. Thyroid function tests were carried out in 16 euthyroid patients, 8 of whom had previously developed thyroid dysfunction during rIFN-alpha therapy for HCV, before, during and after the administration of 10 drops of saturated solution of potassium iodide (SSKI) (approximately 350 mg iodide). All 16 patients had been treated in the past with rIFN-alpha for HCV. Eight patients had developed rIFN-alpha induced abnormalities in thyroid function (5 inflammatory thyrotoxicosis, 1 Graves' disease, and 2 impaired thyroid organification of iodide) and 8 had not developed thyroid dysfunction. After baseline serum free T4 (FT4) and free T3 (FT3) concentrations, basal and TRH stimulated TSH concentrations, and TSH-receptor (TSH-R-Ab) and thyroid peroxidase (TPO-Ab) antibodies were measured, 10 drops saturated solution of potassium iodide (SSKI, approximately 350 mg iodide) were given daily for 60 days and the above parameters assessed during and after SSKI was discontinued. Five of 8 patients with a previous history of rIFN-alpha induced thyroid dysfunction developed mild iodide induced abnormalities of thyroid function (subclinical hypothyroidism (slightly elevated basal and TRH stimulated serum TSH concentrations with normal serum FT4 and FT3 concentrations) or hyperthyroidism) compared with the 8 patients who had no previous evidence of thyroid dysfunction during rIFN-alpha therapy. In view of the present observations, it is prudent to avoid the administration of excess iodine to euthyroid subjects with a previous episode of thyroid dysfunction during rIFN-alpha therapy, adding a new group of patients susceptible to iodine induced thyroid disease.