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Case Reports 2014; 35(5): 335-341 PubMed PMID: 25275265 Citation  Keywords:  Adolescent, Antithyroid Agents:administration & dosage, Autoantibodies:immunology, Child, Child, Preschool, Female, Graves Disease:drug therapy, Hashimoto Disease:drug therapy, Humans, Hypothyroidism:chemically induced, Male, Methimazole:administration & .   

BACKGROUND: The main clinical manifestations of autoimmune thyroid diseases are Graves' disease (GD) and Hashimoto's thyroiditis (HT). Graves' disease is the cause of most cases of hyperthyroidism in childhood. Indications for radical therapy (surgery or 131I treatment) in children are still a matter of discussion, as sustained (sometimes very long) remission of GD is possible, while the radical therapy almost always leads to hypothyroidism. Spontaneous evolution from GD with hyperthyroidism to HT with hypothyroidism may also be observed.

OBJECTIVE: The aim of the study was to analyze the clinical course of 6 cases of hyperthyroid girls with GD in whom a normalization of previously increased autoantibodies against thyrotropin (TSH) receptor (anti-TSHR) was observed together with a significant increase in autoantibodies against thyroid peroxidase (anti-TPO) and thyroglobulin (anti-Tg), with concomitant hypo- or euthyroidism but no recurrence of hyperthyroidism.

SUBJECTS: Patients' age at diagnosis ranged from 5.0 to 16.5 years. Two (2) patients had Turner syndrome, another one (1), diabetic, was on insulin therapy.

RESULTS: In all the girls, antithyroid drugs were administered and euthyroid state was achieved during the first 2.0-3.5 months of the treatment. Mild side effects were observed in only one case. The therapy was continued up to 1.5-4.0 years. Relapses during the therapy were observed in 2 cases. Up to now, no relapses have been observed for 0.5-7.5 years since the therapy withdrawal in 5 patients (1 patient was lost to follow-up), 2 patients are currently treated with levothyroxine due to hypothyroidism.

CONCLUSIONS: It seems that the prolonged pharmacotherapy with antithyroid drugs, followed by observation after remission of hyperthyroidism, may be an appropriate therapeutic option at least in some children with GD as they can be cured without radical therapy and the potential risks of such treatment....

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Journal Article 2012; 33(7): 703-708 PubMed PMID: 23391881 Citation  Keywords:  Animals, Antithyroid Agents:pharmacology, Body Temperature:drug effects, Body Weight:drug effects, Brain Chemistry:drug effects, Eating:drug effects, Energy Metabolism:drug effects, Hypothalamus:drug effects, Hypothyroidism:chemically induced, Male, Methi.   

OBJECTIVES: We evaluated the contribution of the thyroid hormones to the long-term maintenance of feeding behavior and body weight, while distinguishing their direct central effects from those resulting from the metabolic rate in the peripheral tissues.

METHODS: We assessed the effect of hypothyroidism on the long-term (6 months) regulation of food intake, body weight, and energy expenditure in rats. We then generated the recovery of a euthyroid condition in the brain while maintaining a low T3 availability for the peripheral organs, i.e. a combined condition of central euthyroidism with peripheral hypothyroidism, with the aid of a pharmacological combination.

RESULTS: Hypothyroidism caused a decrease in the daily food intake, body weight, and body temperature. The food intake and body temperature stabilized at a lower value, whereas body weight kept decreasing at a constant rate. The administration of exogenous T4 increased food intake and body-weight gain, but had no effect on body temperature.

CONCLUSIONS: The thyroid hormones are necessary for the long-term regulation of energy intake, storage, and expenditure by different mechanisms. The feeding behavior seems to be partially dependent on a direct action of the thyroid hormones on the brain and this effect is independent of the energy expenditure in the peripheral organs. The body weight is closely dependent on the thyroid status and its maintenance seems to involve thyroid action on mechanisms other than feeding and metabolic rate....

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Journal Article 2010; 31(1): 137-146 PubMed PMID: 20150865 Citation  Keywords:  Acetylcysteine:pharmacology, Ambroxol:pharmacology, Animals, Antioxidants:pharmacology, Antithyroid Agents:administration & dosage, Drug Evaluation, Preclinical, Free Radical Scavengers:pharmacology, Injections, Intraperitoneal, Lipid Peroxidation:drug ef.   

OBJECTIVE: A possible role of antioxidants in thyreotoxicosis was investigated. We examined the parameters of lipid peroxidation (LPO): conjugated dienes (CD), malondialdehyde (MDA), Schiff bases (SB) in lung homogenates of male Wistar rats.

METHODS: Two control groups were created: Group 1 - intact animals and Group 2 - animals injected with 0,9% NaCl. In Experiment I, the animals received L-thyroxin (LT4) i.p. (Groups 3-7). After one week the rats received additionally: Group 4 - melatonin (MEL); Group 5 - propylthiouracil (PTU); Group 6 - Ambroxol (AMB); Group 7 - N-acetylocysteine (NAC). In Experiment II, the animals received only antioxidants.

RESULTS: In Experiment I, we noticed a significantly higher MDA and SB level in Group 2, compared to that in Group 1. Moreover, we observed a significantly higher MDA and SB level in Group 3, vs. that in Group 1, but SB level was lower in Group 3 than in Group 2. Melatonin, PTU and NAC reduced CD; PTU, AMB diminished MDA and MEL, AMB lowered SB levels as compared to Group 3. In Experiment II, we observed significantly higher MDA and SB level in Group 2, vs. that in Group 1. Melatonin, AMB and NAC decreased MDA and SB level, when compared to Group 2 but PTU elevated MDA and SB level vs. that in Group 1.

CONCLUSIONS: 1) L-T4 suppresses LPO, 2) MEL, AMB and NAC protect against LPO, 3) PTU is an antioxidant in thyreotoxicosis, however, when administered alone, it enhances LPO, 4) stress accelerate LPO....

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Comparative Study 2007; 28(4): 484-488 PubMed PMID: 17693962 Citation  Keywords:  Aging:physiology, Albinism:genetics, Animals, Antithyroid Agents:adverse effects, Bone Density:drug effects, Bone Development:drug effects, Carbimazole:adverse effects, Hormone Replacement Therapy:methods, Hypothyroidism:chemically induced, Rats, Rats, Mu.   

: To evaluate the effect of carbimazole induced hypothyroidism and thyroxine replacement, on the growth of long bones of albino rats of different age groups. Experimental albino rats were developed with carbimazole and carbimazole plus thyroxine for a period of six weeks. At the end of the experiment the animals were sacrificed, fixed and processed to demonstrate the bony and cartilaginous parts. The ulna and tibia of both sides were measured for intact bone length & diameter and the data compared. The reduction in length and circumference observed, at the end of experiment, in ulna was 10.89%, & 11.94% and in tibia it was 12.52%, 14.81% in carbimazole treated group respectively, while in carbimazole plus thyroxin treated group the reduction in length & circumference of ulna was 1.37% & 1.88% and in tibia it was 1.86% & 3.08% respectively. They were compared to their age matched controls. The reduction in length and circumference in ulna was 5.58% & 6.25% and 6.42% and 5.88% in tibia respectively among the carbimazole treated animals while in the carbimazole plus thyroxine treated animals the reduction was only 0.63% and 3.12% in ulna and 0.91% and 1.06% in tibia respectively. The results show that hypothyroidism and its replacement therapy affects the endochondral as well as periosteal bone growth and results in reduction in length as well as circumference of long bones....

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Comparative Study 2006; 27(5): 595-599 PubMed PMID: 17159816 Citation  Keywords:  Animals, Antioxidants:pharmacology, Antithyroid Agents:pharmacology, Diet, Dose-Response Relationship, Drug, Kidney:chemistry, Liver:chemistry, Lung:chemistry, Male, Oxidative Stress:drug effects, Potassium Iodide:administration & dosage, Propylthiouracil.   

OBJECTIVES: Iodide administration to animals, living in iodine-deficient areas, can induce oxidative processes in the thyroid gland and increase concentration of lipid peroxidation (LPO). Propylthiouracil (PTU)--a well-known antithyroid drug--may also act as an antioxidant. There are some reports, which consider the protective ability of this drug against LPO. The goal of the study was to evaluate oxidative processes and the protective role of PTU in three rat organs during treatment with pharmacological doses of iodide.

MATERIAL AND METHODS: Schiff's bases (SB) concentrations (a parameter of oxidative stress) were measured in liver, lung and kidney homogenates of male Wistar rats. For 2 weeks the animals received iodides in their diet in the following concentrations: Group 1--Controls (standard diet, approx. 0.7 mg of potassium iodide per kg; KI/kg); Group 2--diet containing 0.25 mg KI/kg; Group 3--diet with 4.0 mg KI/kg; Group 4--diet with 8.0 mg KI/kg. Group 5--standard diet with 0.1% of PTU in drinking water for two weeks. Subsequent tree groups (6-8) received KI in their diet in doses as above, respectively, together with PTU.

RESULTS: We noted increased SB levels in the lungs and in the liver, compared to those observed in the control group. We also found decreased SB concentrations in liver and lung homogenates after the administration of PTU but, unexpectedly, the level of SB increased in kidney homogenates of all the groups.

CONCLUSIONS: The results of this study indicate that iodine is involved in oxidative processes in different organs and PTU protects against iodine-induced oxidative stress....

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Comparative Study 2005; 26(6): 704-708 PubMed PMID: 16380675 Citation  Keywords:  Analysis of Variance, Animals, Antioxidants:pharmacology, Antithyroid Agents:pharmacology, Brain:metabolism, Hydrocarbons:metabolism, Lipid Peroxidation:physiology, Male, Malondialdehyde:metabolism, Melatonin:metabolism, Neuroprotective Agents:metabolism,.   

OBJECTIVE: It is known that thyrotoxicosis induces lipid peroxidation (LPO). In contrast, propylthiouracil (PTU), a thyrostatic drug is a well-known antioxidant. Also melatonin has been shown to protect against free radical-induced neuronal destruction. At the same time, it is generally accepted that the brain is the most vulnerable tissue to oxidative stress.

METHODS: The goal of the study was to examine the components of LPO, i.e., conjugated dienes (CD), malondialdehyde (MDA) and Schiff's bases (SB), in the brain of male Wistar rats. Two experiments were performed, with two control groups created for each experiment: Group 1--intact animals and Group 2--animals injected with 0.9% NaCl. In Experiment I, the animals received L-thyroxine (L-T4) in a dose of 100 microg/kg BW, i.p., daily, for two weeks (Groups 3-5). After one week of L-T4 treatment, the following agents were added during a subsequent week: Group 4--PTU in drinking water (45 mg/kg BW/day); Group 5--melatonin (5 mg/kg BW, daily). In Experiment II, lasting 7 days, the animals were divided into the following groups: Group 1--intact animals; Group 2--animals injected with 0.9% NaCl; Group 3--PTU in drinking water (45 mg/kg BW/day); Group 4--melatonin (5 mg/kg BW, daily).

RESULTS: In Experiment I, we observed a significantly higher SB level in saline treated animals and a significant increase in both CD and SB levels in rats treated with L-T4, compared to those in non treated control. CD levels were also elevated in rats treated with L-T4, compared to values in the saline only treated animals. Melatonin and PTU reduced CD levels and melatonin diminished SB levels, as compared to those in L-T4-treated rats. In Experiment II, we observed significantly higher CD, SB and MDA levels in saline treated rats, when compared to respective values in non treated control. Melatonin decreased CD levels, when compared to CD levels in both the non treated and saline injected controls. Additionally, melatonin reduced SB levels relative to change in the brains of saline treated rats. Furthermore, PTU decreased CD levels in brain homogenates compared to non-treated animals.

CONCLUSIONS: (1) L-thyroxine administration stimulates LPO in the rat brain; (2) All the examined antioxidants decrease LPO in L-T4-administered animals; (3) All the examined antioxidants reduce the basal LPO; 4) Stress, when induced by handling, intensifies oxidative processes in the organism....

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Journal Article 2005; 26(5): 536-540 PubMed PMID: 16264404 Citation  Keywords:  Animals, Antithyroid Agents, Cholesterol:blood, Folic Acid:blood, Homocysteine:blood, Hyperthyroidism:blood, Hypothyroidism:blood, Lipids:blood, Male, Propylthiouracil, Rats, Rats, Wistar, Thyroid Function Tests, Thyroxine, Vitamin B 12:blood,.   

INTRODUCTION: It is claimed in a limited number of studies carried out on human beings that plasma homocysteine levels increased in hypothyroid patients and decreased in hyperthyroid patients.

OBJECTIVE: The aim of this study is to determine total plasma homocysteine, thyroid function tests, vitamin B12, folic acid and lipid levels and to explore the relations among them in rat models with induced hypothyroidism and hyperthyroidism with a view to investigating whether hypothyroid and hyperthyroid rat models could represent human hypothyroidism and hyperthyroidism models.

MATERIAL AND METHOD: The study included 30 male Wistar Albino species rats with a mean weight of 200 - 250 g. Rats were randomly divided into 3 groups as 1) hypothyroid group, 2) hyperthyroid group and 3) control group. Hypothyroidism was induced by adding 10 mg/kg/day propylthiouracil to rats' drinking water for 30 days. In order to induce hyperthyroidism, rats were administered 10 microg/100 g L-thyroxin ampule via intraperitoneal route for 10 days.

RESULTS: We found that total plasma homocysteine level of the hypothyroid group was significantly lower than those of the control group (p<0.05) and the hyperthyroid group (p<0.001). Total plasma homocysteine level of the hypothyroid group was found insignificantly higher than that of the control group (p>0.05) and significantly higher than that of the hyperthyroid group (p<0.001). We established a significant and positive correlation between total plasma homocysteine level and thyroid hormone levels. We did not identify a significant relation between total plasma homocysteine level and serum folic acid and serum vitamin B12 levels.

CONCLUSION: Our findings are different from the findings reported in human hypothyroidism and hyperthyroidism studies. We believe that hypothyroid and hyperthyroid rat models cannot represent human hypothyroidism and hyperthyroidism models....

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