Showing papers on "Propylthiouracil published in 1999"

Regulation of sodium iodide symporter gene expression in FRTL-5 rat thyroid cells.

Abstract: The sodium iodide symporter (NIS), first identified in FRTL-5 cells, plays a critical role in iodide transport in the thyroid gland and in the production of the iodine-containing thyroid hormones. The aim of our study was to examine the regulation of NIS RNA steady-state levels and protein expression as well as functional activity in FRTL-5 cells. FRTL-5 cells cycling in media containing thyrotropin (TSH) were incubated for 48 hours with dexamethasone (10-8-10-5 M), triiodothyronine (T3; 10-9-10-6 M), methimazole (100 μM), propylthiouracil (PTU; 100 μM), perchlorate (10 μM) and potassium iodide (40 μM). In other experiments, cells were treated for 48 hours with various cytokines including interleukin-6 (IL-6) (100 U/mL), interferon-γ (IFN-γ) (100 U/mL), tumor necrosis factor-α (TNF-α) (10 ng/ml), IL-1α (100 U/mL), and IL-1β (100 U/mL). Northern blot analysis using a 32P-labeled rat NlS-specific cDNA probe (nucleotides 1397-1937) revealed NIS mRNA as a single species of approximately 3 kb. When normalized ...

Propylthiouracil-induced hypothyroidism reduces xenograft tumor growth in athymic nude mice.

Abstract: BACKGROUND Thyroid hormones are endocrine modulators of several vital processes that are crucial to tumor growth and differentiation. Several anecdotal reports in the literature suggest that some histologic types of carcinoma may remain in a dormant state for prolonged periods of time in patients with hypothyroidism, with eventual progression of the disease once the decreased thyroid function is identified and corrected. METHODS Oral propylthiouracil (PTU) was used to induce hypothyroidism in athymic nude mice that were subsequently inoculated with lung adenocarcinoma and prostate adenocarcinoma cells. Mice were also treated with a combination of PTU and thyroxine, which resulted in hyperthyroid levels of T4. RESULTS Subcutaneous lung and prostate xenografts grew significantly more slowly in hypothyroid mice treated with PTU than in euthyroid or hyperthyroid mice, regardless of treatment with PTU. Tumors grew well in groups of mice that were changed from a hypothyroid state to a euthyroid state by withdrawal of oral PTU. Administration of PTU 3 weeks after tumor inoculation also caused the tumor growth to slow significantly compared with tumors in mice that did not receive PTU. Mice that received PTU and thyroxine had tumors that grew as well as the tumors in euthyroid control animals. CONCLUSIONS Our study indicates that human lung and prostate tumors do not grow well in hypothyroid nude mice, and that rendering these animals euthyroid has a significant impact on the growth rate of these tumors. Furthermore, in vitro and in vivo data indicated that this was not a result of an interaction of the tumor cells with PTU, but rather a result of the hypothyroid state. Cancer 1999;86:1596–601. © 1999 American Cancer Society.

Clinical and biochemical changes following 131I therapy for hyperthyroidism in patients not pretreated with antithyroid drugs

Abstract: Background: Radioiodine therapy (131I) for the treatment of hyperthyroidism has been shown to be effective and safe. Despite the extensive experience with radioiodine therapy, the necessity for pretreatment with antithyroid drugs is controversial. Pretreatment is partly based on the concept that antithyroid drugs deplete the thyroidal hormonal stores, thereby reducing the risk of a radioiodine-induced aggravation of hyperthyroidism or thyroid storm. Few data are available on the frequency of clinically significant exacerbations of hyperthyroidism following 131I therapy without prior treatment with antithyroid drugs. The aim of the present study was to determine prospectively the early clinical and biochemical changes after 131I therapy in patients who were not pretreated with antithyroid drugs. Methods: Patients with Graves’ disease (n=21), toxic multinodular goiter (n=11) or toxic adenoma (n=2) were studied before and after 131 I therapy. Clinical and biochemical parameters of thyroid function were investigated before and 1, 2, 8, 11, 18 and 25 days after 131I treatment. Patients were given no antithyroid drugs prior to 131I therapy, all patients received β-blocking agents for symptomatic relief. Results: In 19 of 34 patients, a transient increase in thyroid hormone levels was observed, predominantly in the first week following 131I therapy. None of these patients experienced worsening of thyrotoxic symptoms. This transient increase in thyroid hormone levels was demonstrated in all patients with toxic multinodular goiter, whereas it was found in only six of 21 patients with Graves’ disease. This difference could not readily be explained by differences in pretreatment thyroid hormone levels, administered dose or effectively absorbed dose of 131I. Conclusions: 131I treatment of hyperthyroidism without pretreatment with antithyroid drugs may cause a transient increase in thyroid hormone levels. Clinically significant exacerbations of hyperthyroidism were, however, not observed in our study population. Increased hormone levels following 131I therapy were more often seen in patients with toxic multinodular goiter than in patients with Graves’ disease.

Resolution of fetal goiter after discontinuation of propylthiouracil in a pregnant woman with Graves' hyperthyroidism.

Abstract: We report a case of Graves' hyperthyroidism in a 34-year-old pregnant woman treated with propylthiouracil (PTU) complicated by the development of a fetal goiter. Because of the fetal goiter and normal maternal thyroid function tests, the PTU was discontinued. Over the next 10 weeks, there was a progressive decrease in the fetal thyroid volume as documented by ultrasonography. The fetal neck returned to a normal flexed position, fetal growth and amniotic fluid remained normal, and the patient remained asymptomatic. A normal infant was delivered at term. This is the first report to demonstrate that noninvasive management may be appropriate for fetuses with goiter caused by antithyroid drug therapy.

Effects of oral propylthiouracil treatment on nitric oxide production in rat aorta.

Abstract: The effects of oral propylthiouracil (PTU) treatment on vascular nitric oxide (NO) production were studied in the rat aorta. Rats were fed a standard low fat diet with or without 0.1% PTU, for 2 or 4 weeks, or for 2 weeks with additional thyroxine injections. Concentration response curves were then constructed to phenylephrine (PE) in both endothelium-intact and denuded aortic rings from these animals and after incubation with 0.1 mM L-N(G)nitroarginine (L-NOARG). In addition, expression of nitric oxide synthase (NOS) was analysed in sections of aorta from PTU-treated and control rats using rabbit polyclonal antibodies to both inducible NOS (iNOS) and endothelial NOS (eNOS). Oral PTU treatment resulted in a significant reduction in both the maximum response (control, 0.53+/-0.02; 2 week PTU, 0.20+/-0.07; 4 week PTU, 0.07+/-0.02 g mg(-1)) and vessel sensitivity (EC50 values: control, 9.10x10(-8)+/-0.67; 2 week PTU, 7.45x10(-7)+/-1.15; 4 week PTU, 9.73x10(-7)+/-0.45 M) to PE in endothelium-intact vessel rings, as compared to controls (P<0.05). Both endothelial removal and incubation with L-NOARG restored the maximum response after 2, but not 4 weeks, although, in general, vessel sensitivity was not altered by either treatment. Vessels from PTU-treated rats given thyroxine injections showed no significant differences between any of the dose response curve parameters. Immunohistochemical analysis suggested that labelling for eNOS may be increased after PTU treatment as compared to control animals, whereas iNOS antibody immunoreactivity was not different between the two groups. These results suggest that the hyporesponsiveness to PE observed after oral PTU treatment is, in part, due to enhanced nitric oxide (NO) production by the endothelium, and demonstrate for the first time that thyroid hormones may play a role in the regulation of eNOS activity in the rat aorta.

Hypothyroidism protects rat liver from acetaminophen hepatotoxicity.

Abstract: Recent data from animal studies suggest thatinduced hypothyroidism inhibits the development of liverinjury in several animal models, including livercirrhosis and fulminant hepatic failure in rats, and immune-mediated acute liver injury in mice. Theaim of the present study was to determine whetherhypothyroidism would likewise preventacetaminophen-induced hepatic damage in rats. Liverdamage was induced by acetaminophen (2 g/kg) administered bygavage to fasting rats as a single dose. Hypothyroidismwas induced by methimazole, propylthiouracil, orsurgical thyroidectomy and confirmed by elevated serum levels of TSH. Hypothyroidism significantlyinhibited acetaminophen-induced liver damage asmanifested by the decreased serum levels of liverenzymes, malondialdehyde and blood ammonia, as well asby the higher hepatic glutathione content, in allthree groups of hypothyroid rats compared to euthyroidcontrols (P < 0.01). Histopathologic analysis showedsignificantly less liver necrosis and inflammation in the acetaminophen-treated hypothyroid rats.Oxygen extraction, measured in isolated perfused ratliver preparation, was also reduced in the hypothyroidlivers to 42 ± 8% compared to 81 ± 14% ofcontrols (P < 0.01). However, the expression ofCYP2E1 in the livers of hypothyroid rats, as measured bywestern blot analysis, was not decreased compared tocontrol rats. These results suggest that inducedhypothyroidism, regardless of the mode of induction, protectsrat liver from acetaminophen hepatotoxicity. This effectmay be related to hypometabolism of liver cells, but theexact mechanism needs further clarification.

Diagnosis and management of maternal and fetal thyroid disorders.

Abstract: Thyroid diseases in pregnancy are a group of disorders with different clinical manifestations which require a rational approach in their diagnosis and management. In many cases, this involves a team approach including different specialties. Several topics have received particular attention in recently published reports. The syndrome of transient hyperthyroidism of hyperemesis gravidarum, more frequently recognized and considered to be caused by inappropriate concentrations of human chorionic gonadotropin in plasma, has been reported for the first time to be secondary to a mutation in the thyrotropin-releasing hormone receptor. Mutations in the thyrotropin-releasing hormone receptor have also being found in cases, most of them familiar, of congenital hypothyroidism caused by resistance to thyrotropin-releasing hormone. However, other cases of congenital hypothyroidism with resistance to thyrotropin-releasing hormone were not caused by mutations in the thyrotropin-releasing hormone receptor. This is a fascinating new field in molecular medicine, stimulated by clinical observations in infants born with congenital hypothyroidism that did not fulfill the classical clinical descriptions. New studies in the metabolism and transfer of anti-thyroid drugs from mother to fetus have indicated no differences between propylthiouracil and methimazole. Finally, changes in titers and the biological action of thyrotropin-releasing hormone receptors antibodies appear to explain the clinical observation of improvement in Graves' hyperthyroidism during the second half of pregnancy and its recurrence during the postpartum period.

Methimazole and propylthiouracil increase cellular thyroid peroxidase activity and thyroid peroxidase mRNA in cultured porcine thyroid follicles.

Abstract: Methimazole (MMI) and propylthiouracil (PTU) are common antithyroid drugs for treating hyperthyroidism because the 2 drugs inhibit thyroid peroxidase (TPO)-catalyzed thyroid hormone formation. We studied whether the 2 drugs actually inhibit cellular TPO activity in cultured porcine follicles. Porcine follicles were cultured in the presence of 1 mU/mL thyrotropin (TSH) for 7 days. Then follicles were exposed to MMI or PTU in the presence of 0.1 microM Kl for 2 days. TPO activity was measured in the 100,000 x g-pellet of the thyroid sonicate by the guaiacol oxidation method. Exposure to MMI (1 microM and 10 microM) or PTU (10 microM and 100 microM) for 2 days caused a significant increase in cellular TPO activity; 100 microM MMI inhibited cellular TPO activity. The presence of cyclic adenosine monophosphate (cAMP)-generating system (forskolin) in TSH-free medium increased MMI-mediated TPO activity. Cyclohexamide inhibited MMI-mediated TPO activation, indicating that new protein synthesis is required for increased TPO activity. Reverse transcriptase-polymerase chain reaction (RT-PCR) showed an increase in TPO mRNA by PTU or MMI. In conclusion, MMI and PTU at therapeutic concentrations can increase TPO mRNA and cellular TPO activity, although the 2 drugs inhibit the TPO-H2O2-mediated catalytic reaction.

A case of ectopic thyroid in lateral neck associated with Graves' disease.

Abstract: Thyroid follicles in the lateral position of the neck are usually thought to represent the metastasis of thyroid carcinoma. Here we present a case of a 28-year-old woman with accessory ectopic thyroid associated with Graves' disease. Despite a history of Graves' disease poorly controlled with large dose propylthiouracil she was found to be pregnant and artificial abortion was planned. Thyroid scintigraphy was carried out, which indicated an uptake into the region above the left lobe as well as into both lobes of the thyroid gland. In order to control hyperthyroidism and to exclude the possibility of metastasis, total thyroidectomy with tumor resection was performed before the artificial abortion. Pathological examinations of the thyroid gland indicated findings compatible with Graves' disease. The lateral neck mass was revealed to be composed of nonneoplastic thyroid tissue, showing similar histological findings to those of the goiter, which were consistent with Graves' disease. Taken together with several previous reports, it appears that there are some cases with lateral ectopic thyroid tissue, whose pathogenetic mechanism remains to be elucidated.

Regulation of thymosin beta10 expression by TSH and other mitogenic signals in the thyroid gland and in cultured thyrocytes.

Abstract: Objective: To investigate the expression of thymosin b10 ‐ a small conserved acidic protein involved in the inhibition of actin polymerization ‐ in human and experimental thyroid goiters as well as the regulation exerted by TSH on thymosin b10 expression in thyroid follicular cells both in vivo and in vitro. Design: To this aim, we have used 5 bioptic specimens from patients affected by thyroid goiter, a well known experimental model of thyroid goitrogenesis (rat fed with the drug propylthiouracil) and a cultured rat thyroid cell line (PC Cl 3 cells) as a model system. Results: We report that the mRNA expression of thymosin b10 is markedly enhanced in human goiters compared with normal thyroid. In vivo results showed that the steady-state level of thymosin b10 mRNA is up-regulated in the thyroid gland of propylthiouracil-fed rats in parallel with follicular cell proliferation: iodide administration to goitrous rats, which induced a marked involution of thyroid hyperplasia, reduced the mRNA level of thymosin b10. Finally, in vitro studies showed that in cultured rat thyrocytes, the expression of thymosin b10 mRNA is induced in a time- and dose-dependent manner by the activation of pathways which are mitogenic for thyroid cells (i.e. the protein kinase (PK) A and PKC pathways). Conclusion: Taken together, the findings reported here demonstrate that thymosin b10 expression is regulated by extracellular signals that stimulate growth of thyroid cells both in vitro and in vivo, and suggest a role for this protein in thyroid diseases characterized by proliferation of follicular cells.

Iopanoic acid-induced decrease of circulating T3 causes a significant increase in GH responsiveness to GH releasing hormone in thyrotoxic patients

Abstract: Objective Thyroid hormones participate in GH synthesis and secretion, and an impaired GH response to many pharmacological stimuli, including GH releasing hormone (GHRH), has been found in thyrotoxicosis. Although the mechanisms involved in this process have not been fully elucidated, there is evidence that thyroid hormones could act at both hypothalamic and pituitary levels. There are no data in the literature about the effect of an acute reduction of circulating T3 levels on GH secretion in hyperthyroidism. The GH responsiveness to GHRH was therefore evaluated in a group of hyperthyroid patients during short-term treatment with iopanoic acid. Iopanoic acid is a compound that induces a rapid decrease in serum T3 levels, mainly by inhibition of peripheral conversion of T4 to T3. To the authors' knowledge, there is no evidence of a direct effect of iopanoic acid on GH secretion. Design Hyperthyroid patients were submitted to a GHRH test (100 microg, i.v.) before (day 0), and on days 4, 7 and 15 after oral treatment with iopanoic acid (3 g every 3 days) and propylthiouracil (200 mg every 8 h). A group of normal control subjects was also submitted to a single GHRH test (100 microg, i.v.). Patients Nine patients with thyrotoxicosis (eight women, one man), with a mean age of 34 years, were studied. All patients had high serum levels of total T3 and total T4, and suppressed TSH levels. None of them had taken any medication for at least 3 months before the study. The patients were compared with a group of nine control subjects (five women, four men) with a mean age of 31 years. Measurements GH and TSH were measured by immunofluorometric assays. Total T3, total T4 and IGF-I were determined by radioimmunoassay. Albumin levels were measured by a colorimetric method. Results Iopanoic acid induced a rapid and maintained decrease in serum T3 concentrations, with a significant reduction on days 4, 7 and 15 compared with pre-treatment values. In hyperthyroidism, peak GH levels (mean +/- SE mU/l) after GHRH were significantly higher on day 15 (24.4 +/- 3.8) than those observed on days 0 (14.2 +/- 1.6), 4 (15.2 +/- 3.0) and 7 (19.6 +/- 5.0). There was a 79% increase in this response on day 15 compared with the pre-treatment period. Hyperthyroid patients had a blunted GH response to GHRH on days 0, 4 and 7 in comparison with control subjects. However, on day 15, no differences were observed between the area under the curve (mean +/- SE mU/l.120 min) in thyrotoxic patients (1770 +/- 306) and in the control group (3300 +/- 816). IGF-I and albumin levels did not change during iopanoic acid administration. Conclusions The results show that an acute reduction in serum T3 levels elicits an increase in GH responsiveness to GHRH in hyperthyroidism. Although the mechanisms involved in this process are still unknown, it is possible that T3 influences GH responsiveness to GHRH via hypothalamic somatostatin release. Alternatively, T3 could have a direct effect at the pituitary somatotroph, modulating GHRH intracellular pathways.

Fetal pituitary negative feedback at early gestational age.

Abstract: We describe an early prenatal diagnosis and the successful treatment of fetal Graves' disease from transplacental transfer of maternal thyroid stimulating autoantibodies (TSAb). The diagnosis of fetal thyrotoxicosis was made by umbilical cord sampling (UBS) at 20 weeks gestation, based on suppressed TSH with elevated FT4 levels. Therapy with propylthiouracil (PTU) improved fetal thyroid function tests as well as the clinical signs of fetal Graves' disease. Three more UBS were conducted before delivery indicating persisting mild fetal hyperthyroidism. Undetectable concentrations of thyrotrophin in fetal serum in the presence of markedly elevated FT4, suggests pituitary negative feedback at as early as 20 weeks gestation. Amniotic fluid thyrotrophin levels were measured at 20,24 and 26 weeks and were shown to correlate better with (elevated) maternal rather than (suppressed) fetal TSH values; therefore, we believe that amniotic fluid thyrotrophin measurement is unreliable for prediction of fetal thyroid status. Our observation is the first documentation of an intact feedback mechanism so early in fetal development and it suggests that pituitary maturation occurs earlier than previously believed.

Effect of PTU treatment on histone acetylation pattern in the developing rat brain.

Abstract: The effect of hypothyroidism induced m female rats on histone acetylation pattern m the neonatal rat brain was studied. It is likely that thyroid hormone regulates the acetylation of histones and thereby influence their interaction with DNA and modulates transcription. Propylthiouracil (PTU), administered to induce hypothyroidism, resulted in a significant reduction m the thyroid and brain weight of neonatal rats. The circulating thyroxine levels were undetectable in both 14 and 21 day old pups. The hypothyroid condition was further confirmed by low levels of T4 (94.31 ng/g brain tissue vs 1811.29 ng/g in controls and 144.67 ng/g vs 1087.72 ng/g in controls at 14 and 21 days, respectively) and T3 (42.19 ng/g brain tissue vs 879.97 ng/g in controls and 60.62 ng/g vs 766.68 ng/g in controls at 14 and 21 days, respectively) in the neonatal rat brain. Histone acetylation pattern was similar in treated and control groups m the 14 day old rats. PTU treatment, however, resulted in significant (p < 0.01) reductio...

The use of recombinant human G-CSF in the treatment of propylthiouracil-induced agranulocytosis

Abstract: A 43-year-old female patient with Basedow-Graves' disease developed agranulocytosis in the eighth month of propylthiouracil therapy. After discontinuing the drug, a broad spectrum antibiotic regimen plus recombinant human granulocyte colony-stimulating factor (G-CSF), a human haematopoietic growth factor, were started. Her granulocyte count returned to normal with the second dose of G-CSF, and ulcerating pharyngitis improved rapidly. We think that in patients with propylthiouracil-induced agranulocytosis, G-CSF will reduce the risk and severity of infection, and should be accepted as a part of the standard therapy.

A de novo L330S point mutation in thyroid hormone receptor beta gene in a Thai female with resistance to thyroid hormone.

Abstract: In the present study, we report a Thai female with a de novo mutation in thyroid hormone receptor-β (TRβ) gene causing resistance to thyroid hormone (RTH). The patient was a 19 year-old woman who presented with goiter for 1 year. Except for tachycardia she had no signs of thyrotoxicosis. Previously she was treated with propylthiouracil based on the diagnosis of thyrotoxicosis for 9 months and her goiter became more enlarged. The patient was the only child of the family. Her parents were alive and healthy, and did not have goiter or any other thyroid diseases. Physical examination revealed no sign of thyrotoxicosis. Her thyroid gland was diffusely enlarged with an estimated weight of 100gm. Laboratory determinations revealed elevated free T4, T3 and nonsuppressed TSH levels. Exon 9 of the TRβ gene was amplified by PCR and the DNA sequence was determined by dye terminator cycle sequencing. Heterozygous point mutation in which T was replaced by C was detected at position 1274 (TTG to TCG) corresponding to a leucine to serine substitution at codon 330. No mutation was found in the parents indicating that the mutation was de novo. The nucleotide change created a restriction site for Taq 1 restriction endonuclease and the mutation was confirmed by restriction fragments length polymorphism. The same nucleotide change has been reported in a family with RTH.

Autoimmune thyroiditis and myelosuppression following treatment with interferon-alpha for hepatitis C.

Abstract: Case: We describe the case of a - 48-year-old woman from Thailand diagnosed - with chronic hepatitis C, who experienced a suppression of all blood cell counts accompanied by a newly developed clinically manifested autoimmune thyroid disorder after treatment with interferon α-2b (INF-α) 46 days after beginning of therapy a decrease of platelet, red and white blood cell counts became obvious. Concomitantly we observed an increase of FT4 and FT3 with a totally depressed TSH level 80 days after starting INF-α administration. Antibody assessment resulted in detection of high numbers of antithyroid-microsomal antibodies and antithyroglobulin antibodies. Thyroid hormone levels normalized under treatment with methimazole/propylthiouracil within 4.5 months. However, two months after cessation of antithyroid therapy increasing TSH levels and decreasing FT4 levels indicated a new tendency towards a hypothyroid state. Conclusion: We classify this case as an interferon-α-induced disorder of thyroid function accompanied by myelosuppression. A close monitoring for thyroid dysfunction, e.g. evaluation of TSH-levels before and after administration of INF-α is mandatory.

Thymidine kinase activity in homogenates of rat thyroid lobes from euthyroid, hypothyroid and/or hyperthyroid rats incubated with EGF: studies ex vivo in vitro.

Abstract: OBJECTIVE To examine thymidine kinase (TK - ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21) activity in homogenates of rat thyroid lobes incubated in vitro with epidermal growth factor (EGF). METHODS The thyroid lobes were collected from euthyroid, hypothyroid and/or hyperthyroid animals. Hypothyroidism was developed in the experimental rats by an administration of 0.1 % solution of propylthiouracil (PTU) in drinking water for 2 weeks, while hyperthyroidism was obtained by daily i.p. injections of L-thyroxine (50 microg/kg, B.W.), also for 2 weeks. After collecting, the thyroids were incubated for 4 hours in RPMI 1640 medium with an addition of 20 mM of Hepes buffer, 15% FCS, penicillin (200 U/ml), streptomycin (10 ug/ml) and with EGF (Sigma) (0.1 ng/ml, 10 ng/ml, 1000 ng/ml). The control lobes were incubated without any addition of EGF to the medium. TK activity was expressed as the amount of reaction products, measured by ascending chromatography. RESULTS 1. in the absence of EGF, TK activity in the homogenates of thyroid lobes from hypothyroid rats was lower, while it was higher in the lobes from hyperthyroid animals, when compared to these obtained from euthyroid controls; 2. EGF in the concentration of 0.1 ng/ml or 1000 ng/ml decreased, while that in the concentration of 10 ng/ml increased TK activity in lobes collected from euthyroid or hyperthyroid rats; 3. in the tissue collected from hypothyroid rats, the addition of EGF (0.1 ng/ml or 10 ng/ml) caused a slight increase in TK activity versus hypothyroid controls - a tendency towards diminishing TK activity could be observed as parallel to increasing EGF concentration. CONCLUSIONS TK activity in the homogenates of rat thyroid lobes depends on the functional thyroid status and on applied EGF concentration in vitro.

Effects of Thyroid Hormone on Serum Insulin-Like Growth Factor Binding Proteins (IGFBPs) and IGFBP-2 mRNA Expression in Chickens

Abstract: We examined serum IGF binding proteins (IGFBPs) and tissue (liver, kidney and brain) IGFBP-2 mRNA in 5-weeks-old cockerels with different thyroidal status to elucidate a possible role of thyroid hormone on IGFBPs in the chicken. Assay for serum IGFBPs by Western ligand blot detected three IGFBPs having molecular masses of 30, 36 and 41 kDa. The 125I-IGF-I bindings to these IGFBPs were significantly decreased in propylthiouracil (PTU) induced hypothyroid cockerels, and restored to euthyroid control levels by thyroxine (T4) supplement. T4 supplement to euthyroid birds had no significant influence on 125I-IGF-I binding to IGFBPs. The expression of IGFBP-2 mRNA in the liver was significantly reduced in hypothyroidism and restored to normal level by T4 replacement, whereas T4, injected to intact birds, failed to affect hepatic IGFBP-2 mRNA expression. In contrast, the expression of IGFBP-2 mRNA in the kidney was increased in hypothyroid birds and decreased both in T4-treated intact and hypothyroid birds. In the brain, IGFBP-2 mRNA level was not influenced by the changes in thyroidal status. IGFBP-2 mRNA was detected in all tissues examined, with varying degree. The expression was higher in the testis, gizzard, brain, eye and bursa of fabricius, followed by kidney and digestive organs. In the liver, the expression was very low compared with other tissues.

Medical therapy of benign thyroid diseases.

Abstract: Main guide-lines of medical therapy of benign thyroid diseases are reviewed The most common drug therapy of the various forms of hyperthyroidism is represented by thionamide drugs (methimazole and propylthiouracil) Therapeutic protocols are diversified according to the disease In Graves'disease medical therapy may present the definitive treatment, leading to remission in little less than 50% of cases while in hyperfunctioning nodular thyroid diseases, medical therapy is merely in preparation for ablation therapy Other drugs used in hyperthyroidism are also mentioned (inorganic iodine, potassium perchlorate, beta-blockers) Thyroxine replacement therapy in the various forms of hypothyroidism is then analyzed, discussing in particular the therapeutic protocols and follow-up of the various forms of hypothyroidism Finally, the controversy about the indications and efficacy of TSH-suppressive thyroxine therapy is considered