Showing papers on "Propylthiouracil published in 2008"
TL;DR: The results indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system, and particularly in patients with hypothyroidism.
Abstract: Background Free radical-mediated oxidative stress has been implicated in the etiopathogenesis of several autoimmune disorders. Also, there is growing evidence supporting the role of reactive oxygen species in the pathogenesis of thyroid disorders. The aim of this study was to investigate the influence of hypothyroidism, hyperthyroidism, and their treatments on the metabolic state of oxidative stress, and antioxidant status markers. Methods A total of 20 newly diagnosed patients with overt hypothyroidism due to Hashimoto's thyroiditis, 20 patients with overt hyperthyroidism due to Graves' disease, and 20 healthy subjects as the control group were enrolled in the study. Fasting blood samples (12 h), taken at the initiation, after the 30th and 60th day of therapy were analyzed for malondialdehyde, nitrite, vitamin E, vitamin A, beta-carotene, ascorbate, and myeloperoxidase and superoxide dismutase activity. No patient presented additional risk factors for increased reactive oxygen species levels. Results Malondialdehyde, nitrite, vitamin E, and myeloperoxidase activity increased in patients with hypothyroidism. After 2 months, the levels of nitrite and vitamin E were reduced to control levels by treatment. The patients with hyperthyroidism had increased levels of malondialdehyde and myeloperoxidase activity in comparison with the controls. Treatment with propylthiouracil attenuated these increments after 1 month. Conclusions Our results reveal an increased generation of reactive oxygen species and impairment of the antioxidant system in patients with hyperthyroidism, and particularly in patients with hypothyroidism. These findings indicate that thyroid hormones have a strong impact on oxidative stress and the antioxidant system.
165 citations
TL;DR: When thyroid hormone production was reduced by PTU, high doses of LT(4) (3.7 microg/kg) were needed to normalize serum TSH, confirming that mutation of MCT8 is a cause of resistance to thyroid hormone.
Abstract: Context: Mutations of the monocarboxylate transporter 8 (MCT8) gene determine a distinct X-linked phenotype of severe psychomotor retardation and consistently elevated T3 levels. Lack of MCT8 transport of T3 in neurons could explain the neurological phenotype. Objective: Our objective was to determine whether the high T3 levels could also contribute to some critical features observed in these patients. Results: A 16-yr-old boy with severe psychomotor retardation and hypotonia was hospitalized for malnutrition (body weight = 25 kg) and delayed puberty. He had tachycardia (104 beats/min), high SHBG level (261 nmol/liter), and elevated serum free T3 (FT3) level (11.3 pmol/liter), without FT4 and TSH abnormalities. A missense mutation of the MCT8 gene was present. Oral overfeeding was unsuccessful. The therapeutic effect of propylthiouracil (PTU) and then PTU plus levothyroxine (LT4) was tested. After PTU (200 mg/d), serum FT4 was undetectable, FT3 was reduced (3.1 pmol/liter) with high TSH levels (50.1 mU/li...
93 citations
TL;DR: Altered patterns of gene expression during critical windows of brain development indicate that thyroid disease must be viewed as a continuum and that conditions typically considered ‘subclinical’ may induce structural and functional abnormalities in the developing central nervous system.
Abstract: Hypothyroidism during pregnancy and the early postnatal period has severe neurological consequences for the developing offspring. The impact of milder degrees of perturbation of the thyroid axis as encompassed in conditions of subclinical hypothyroidism and hypothyroxinemia, however, has not been established. The present investigation examined the effects of graded levels of hypothyroidism, from subclinical to severe, on global gene expression in the developing rodent brain. Thyroid hormone insufficiency was induced by administration of propylthiouracil (PTU) to pregnant rats via drinking water from gestational day 6 until sacrifice of pups prior to weaning. In the first study a specialised microarray, the Affymetrix Rat Neurobiology array RN_U34, was used to contrast gene expression in the hippocampus of animals exposed to 0 or 10 ppm (10 mg/l) PTU, a treatment producing severe hypothyroidism. In the second study, a more complete genome array (Affymetrix Rat 230A) was used to compare gene expression in the neocortex and hippocampus of postnatal day (PN) 14 animals experiencing graded degrees of thyroid hormone insufficiency induced by delivery of 0, 1, 2 or 3 ppm PTU to the dam. Dose-dependent up- and down-regulation were observed for gene transcripts known to play critical roles in brain development and brain function. Expression levels of a subset of approximately 25 genes in each brain region were altered at a dose of PTU (1 ppm) that induced mild hypothyroxinemia in dams and pups. These data indicate that genes driving important developmental processes are sensitive to relatively modest perturbations of the thyroid axis, and that the level of gene expression is related to the degree of hormone reduction. Altered patterns of gene expression during critical windows of brain development indicate that thyroid disease must be viewed as a continuum and that conditions typically considered 'subclinical' may induce structural and functional abnormalities in the developing central nervous system.
82 citations
TL;DR: Results showed that PTU-induced hypothyroxinemia influenced the developing rat brain, and that all effects on behaviour and loss of hearing in the adult offspring were significantly correlated to reductions in T(4) during development, which supports the hypothesis that decreased T( 4) may be a relevant predictor for long-lasting developmental neurotoxicity.
75 citations
TL;DR: Excellent maternal and fetal outcomes can be achieved with appropriate management of thyroid dysfunction in pregnancy with careful control of maternal disease whilst avoiding fetal hypothyroidism.
Abstract: Background: Uncontrolled thyroid dysfunction in pregnancy is associated with adverse fetal and maternal outcomes. Objectives: To review relevant literature and developments in the medical management of thyroid dysfunction in pregnancy. Results: Hyperthyroidism in pregnancy requires careful control of maternal disease whilst avoiding fetal hypothyroidism. Propylthiouracil is the preferred antithyroid drug in pregnancy although thiamazole can be used where propylthiouracil is unavailable. Synthetic levothyroxine is the treatment of choice in hypothyroidism. Patients with pre-existing hypothyroidism will generally require an increase in thyroxine dose in pregnancy. Most patients with postpartum thyroiditis will require treatment during the hypothyroid phase. Long-term follow-up of patients with this syndrome is essential owing to the risk of permanent hypothyroidism. Conclusion: Excellent maternal and fetal outcomes can be achieved with appropriate management of thyroid dysfunction in pregnancy.
45 citations
TL;DR: The results show that curcumin activity depends on the functional condition of the rat thyroid which changes with age, and this compound exerts stimulatory influence on the secretory function of the thyroid gland in young rats, but has rather weak antithyroid activity in old animals.
Abstract: The aging is associated with alterations in the hypothalamic-pituitary-thyroidal axis which can lead to hypothyreosis. Our previous investigations has shown that polyphenol curcumin can enhance the manifestation of hypothyreosis in rats simultaneous treated with propylthiouracil. The aim of the study was to investigate the relationship between age-related changes and curcumin action in the thyroid of old rats. To this end, morphometric and radioimmunological methods were used. The study was conducted on 3- and 18-month-old male Wistar rats. The experimental rats were treated daily for 30 days by gavage with 100 mg/kg b.w. of curcumin. There were observed age-related changes in morphology and endocrine function of the thyroid. It was increase in the percentages of large follicles and significant decrease in FT3 level in 18-month-old rats in comparison to 3-month ones. Curcumin treatment lead to significant increase in FT3 and FT4 levels in 3-month-old experimental rats, but the level of FT3 significantly decreased in 18-month-old rats after curcumin administration. Our results show that curcumin activity depends on the functional condition of the rat thyroid which changes with age. This compound exerts stimulatory influence on the secretory function of the thyroid gland in young rats, but has rather weak antithyroid activity in old animals.
22 citations
TL;DR: During depletion of serum T(4), D2 activity served as a sensitive marker of tissue thyroid status, an indicator of the brain's compensatory response to maintain cT(3), and correlated with a neurophysiological outcome.
Abstract: The developing central nervous system of the fetus and neonate is recognized as very sensitive to maternal or gestational hypothyroidism. Despite this recognition, there is still a lack of data concerning the relationship between thyroid-related biomarkers and neurological outcomes. We used propylthiouracil administered at 0, 3, or 10 ppm in drinking water from gestational d 2 until weaning to create hypothyroid conditions to study the relationship between hypothalamic-pituitary-thyroid axis compensation and impaired neurodevelopment. In addition to serum T(3), T(4), free T(4), and TSH concentrations, cerebrocortical T(3) concentration (cT(3)), hepatic type I and cerebrocortical type II (D2) 5'-deiodinase activity, and thyroidal mRNA for thyroglobulin and sodium iodide symporter were measured. Extracellular recordings from the CA1 region in hippocampal slices were obtained from both postnatal d 21-32 (pups) and postnatal d 90-110 (adults) rats to assess neurophysiological effects. Thyroidal mRNA for thyroglobulin and sodium iodide symporter were increased in pups but not in dams. Both propylthiouracil doses increased cerebrocortical D2 activity approximately 5-fold in pups but only 10 ppm increased D2 activity in dams. In dams, cT(3) concentrations were maintained at 3 ppm but fell 75% at 10 ppm. cT(3) concentration in pups fell 50% at 3 ppm and more than 90% at 10 ppm. In both 3 and 10 ppm pups, hippocampal baseline synaptic activity correlated negatively with cerebrocortical D2 activity. In 3 ppm adults, impaired long-term potentiation was evident. In summary, during depletion of serum T(4), D2 activity served as a sensitive marker of tissue thyroid status, an indicator of the brain's compensatory response to maintain cT(3), and correlated with a neurophysiological outcome.
20 citations
TL;DR: In normal instances the lowest possible dosage should be administered to control hyperthyroid metabolism, and long-term treatment with low doses seem to be without problems.
Abstract: Side effects of antithyroid treatment were retrospectively analysed in 1256 patients with hyperthyroidism. Overall rate of side effects was 14.3%. Skin reactions were the most frequent ones (5.6%), followed by arthropathies (1.6%). The incidence of agranulocytosis was 0.14%. Median duration of all side effects was 1.5 months. In half the cases the side effects were controllable so that treatment was continued, although at a changed dosage. The rate of cross-reaction between carbimazole and thiamazole, on the one hand, and propylthiouracil, on the other, was 13.8% and 15.2%, respectively. The side effects became apparent after a mean of one month's treatment, almost always (in 97.1%) within the first year of treatment. There was a significant dose dependence for an initial thiamazole dose of over 20 mg (relative side effect risk of 2.3), and for an initial dose of over 30 mg for carbimazole (relative side effect risk of 1.6). Although most side effects were not dangerous, in normal instances the lowest possible dosage should be administered to control hyperthyroid metabolism. Long-term treatment with low doses seem to be without problems.
19 citations
TL;DR: Preoperative ATD treatment duration may predict intraoperative blood loss during thyroidectomy, and longer treatment duration might be useful in reducing intraoperative bleeding, allowing better visualization and preservation of the nerves and parathyroid glands.
19 citations
TL;DR: It is shown that the administration of either propylthiouracil or thyroid hormones results in an increased activity of the microsomal ethanol-oxidizing system, suggesting that the underlying mechanism for the induction of the Microsomal Ethanol-Oxidizing System by Propylthaviouracil is independent of the action of thyroid hormones.
Abstract: Treatment for 7 days with the thyreostatic drug propylthiouracil (5 mg/100 g of body weight) resulted in a hypothyroid hepatic state as shown by the marked decreased hepatic content of thyroxine and triiodothyronine. This regimen led to an enchanced activity of the microsomal ethanol-oxidizing system, whereas the activities of alcohol dehydrogenase and catalase remained unchanged. Moreover, a hyperthyroid hepatic state achieved following the daily administration of L-thyroxine (150 micrograms/100 g of body weight) or L-3,3', 5-triiodothyronine (10 micrograms/100 g body weight) for 7 days resulted in a similar increased activity of the microsomal ethanol-oxidizing system. Under these conditions, a decrease of alcohol dehydrogenase activity and an unaffected catalase activity was observed. These findings, therefore, show that the administration of either propylthiouracil or thyroid hormones results in an increased activity of the microsomal ethanol-oxidizing system, suggesting that the underlying mechanism for the induction of the microsomal ethanol-oxidizing system by propylthiouracil is independent of the action of thyroid hormones.
14 citations
TL;DR: This case demonstrates the rare case of a TSH-secreting adenoma in a young patient, which was complicated by the development of postoperative thyroid storm.
TL;DR: It was demonstrated that PTU produced endothelium-dependent vasodilatation through thyroid-independent and NO-mediated mechanisms that may contribute to its beneficial effect on atherosclerosis.
TL;DR: In this paper, a mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of resistance to thyroid hormone (RTH).
Abstract: BACKGROUND: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome characterized by decreased responsiveness of target tissues to thyroid hormone. Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH). METHODS: The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as having multinodular toxic goiter which was treated with antithyroid drugs and partial thyroidectomy. Her younger son had attention deficit hyperactivity disorder and primary encopresis, but normal intellectual quotient. Both had elevated serum iodothyronine levels with nonsuppressed thyrotropin. RESULTS: A mutation in one allele of the thyroid hormone receptor beta gene (P453A) was identified, providing a genetic confirmation for the diagnosis of RTH. CONCLUSION: Mutational analysis of the TRs gene allows definitive diagnosis of RTH, potentially avoiding the need for protracted and expensive pituitary function testing.
TL;DR: A case of alveolar haemorrhage secondary to PTU-induced vasculitis, with complete resolution after discontinuation of PTU is reported.
Abstract: Dear Sir, Thionamide-induced vasculitis is a multisystem disease that can affect any organ system. Propylthiouracil (PTU) is responsible for the majority of cases and the predominant anti-neutrophils cytoplasmic antibodies (ANCA) pattern on immunofluorescent staining is P-ANCA [1]. We report a case of alveolar haemorrhage secondary to PTU-induced vasculitis, with complete resolution after discontinuation of PTU.
TL;DR: The induction and detection systems of hsp‐72 using FRTL5 cells would facilitate future studies, and suggest that aberrantly expressed hsp may activate part of the thyroid‐infiltrating lymphocytes and thereby aggravate autoimmune processes, to explore possible relations between stress proteins and thyroid autoimmunity.
Abstract: In Graves' disease and Hashimoto's thyroiditis, the presence of 72-kD heat shock protein (hsp-72) on thyrocytes has been reported. To clarify the significance of this phenomenon, we induced the antigen in thyroid cell culture in vitro. In the FRTL5 rat cell line, which had been heated at 42.5 degrees C or treated with sodium arsenite, expression of hsp-72 was examined with immunoperoxidase staining and immunoprecipitation of the metabolically labelled protein using a specific MoAb. In the cells cultured either with or without thyrotropin (TSH), heat and chemical stresses reproducibly and dose-dependently induced hsp-72 antigen, whereas unstimulated controls had no significant immunoreactivity. Unlike in Graves' retrocular fibroblasts, hydrogen peroxide was not an effective stress in FRTL5, and the induction was not suppressed by methylmercaptoimmidazole and propylthiouracil, nor enhanced by interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). These data could not support the hypotheses that suppression of thyroid autoimmunity by thionamides is due to their modulatory action on hsp-72 expression, or that presence of that antigen in the thyroid tissues affected by autoimmunity is secondary to cytokine secretion from infiltrating immunocytes. On the other hand, coculture experiments of stressed FRTL5 cells and syngeneic Fisher rat splenocytes suggest that aberrantly expressed hsp may activate part of the thyroid-infiltrating lymphocytes and thereby aggravate autoimmune processes. The induction and detection systems of hsp-72 using FRTL5 cells would facilitate future studies, possibly utilizing human materials as well, to explore possible relations between stress proteins and thyroid autoimmunity.
TL;DR: Second trimester subtotal thyroidectomy was safe and effective in treating this pregnant patient’s thyrotoxicosis and highlights the association of propylthiouracil induced ANCA positivity and agranulocytosis.
Abstract: Background
Thionamide induced agranulocytosis is associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) in some patients. This poses a particular challenge when it occurs during pregnancy.
Journal Article•
TL;DR: A young female patient suffering from Graves' disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy, and her long-term prognosis remains uncertain.
Abstract: A young female patient suffering from Graves. disease is presented, who raised some diagnostic and therapeutic dilemmas after being diagnosed with subclinical hyperthyroidism following total thyroidectomy. This 20-year-old female patient, carrier of HLA B8 DR3 genes, was referred to our hospital for total thyroidectomy after developing severe leukopenia on both methimazole and propylthiouracil therapy. A high postoperative titer of thyrotropin receptor antibodies and positive scintigraphy finding of the pyramidal lobe and remnant thyroid tissue in the left thyroid lobe led to the administration of radioiodine. Despite further enlargement of the remnant thyroid tissue on post-radioiodine scintiscanning, the patient is currently euthyroid, with normal thyroid-stimulating hormone levels ; however, her long-term prognosis remains uncertain.
TL;DR: It was concluded that the thyroid and ovarian hypofunction have distinct effects on the spleen and that in the hypothyroidism-hypogonadism association, the increase in the apoptosis index and in the expression of splenic caspase 3 is not as much as in isolated hyp Timothyroidism.
Abstract: Apoptosis, proliferation and histomorphometry of spleen were investigated in ovariectomized and non-ovariectomized adult Wistar rats maintained in hypothyroidism induced by daily administration of propylthiouracil (PTU) during 120 days. Two groups ovariectomized euthyroid and non-ovariectomized euthyroid were used as controls. Plasma was collected for free T4 dosage and the spleen for histomorphometry analysis, apoptosis index and the immunohistochemistry expression of caspase 3 and CDC47. Values of free T4 were lower in rats treated with PTU (p<0.05). In the hypothyroid groups there was some decrease in the spleen weight as well as the number and size of lymphoid follicles and there was some increase in the apoptotic index and the caspase 3 expression (p<0.05). However, the increase in the apoptosis index and the expression of caspase 3 in ovariectomized hypothyroid rats spleen was less accentuated than non-ovariectomized hypothyroid ones (p<0.05). The ovariectomized euthyroid group presented white pulp hyperplasia in comparison to the non-ovariectomized euthyroid group. There was no difference in the CDC47 expression between groups. It was concluded that the thyroid and ovarian hypofunction have distinct effects on the spleen and that in the hypothyroidism-hypogonadism association, the increase in the apoptosis index and in the expression of splenic caspase 3 is not as much as in isolated hypothyroidism.
TL;DR: A case of an 8-day-old preterm neonate with heart failure, pulmonary hypertension, and myocardial ischemia due to hyperthyroidism is reported, which has not been previously reported in neonates.
Abstract: A case of an 8-day-old preterm neonate with heart failure, pulmonary hypertension, and myocardial ischemia due to hyperthyroidism is reported. Treatment of the disease initially with b-blockers and, upon establishment of hyperthyroidism, with propylthiouracil reversed all cardiac abnormalities. Contrary to the rule, diagnosis of hyperthyroidism in the mother was established following the diagnosis of the condition in her baby. On long-term follow-up (10 years), the child has developed normally, remains euthyroid with normal electrocardiogram. To our knowledge, diagnosis and reversal of the above-mentioned ischemic abnormalities have not been previously reported in neonates.
TL;DR: A case of a young man with thyroid storm and an underlying papillary thyroid carcinoma, who later underwent thyroidectomy, highlights the importance of prompt recognition and treatment of thyrotoxic crisis and importance of screening for concurrent thyroid carcinomas.
Abstract: We describe a case of a young man with thyroid storm and an underlying papillary thyroid carcinoma. This case highlights the importance of prompt recognition and treatment of thyrotoxic crisis and importance of screening for concurrent thyroid carcinoma. An 18-year-old previously healthy man was admitted with fever and left retro-orbital abscess. A diagnosis of thyroid storm was made based on physical examination and laboratory investigations. Patient underwent an urgent decompression of abscess. Septic shock, shock liver, DIC and renal failure complicated perioperative course. The patient was managed with supportive treatment and multiple medications, including propylthiouracil. Patient later underwent thyroidectomy and the biopsy showed a background pattern of Graves disease, Hurthle cells adenoma, and multicentric subcentimeter of papillary thyroid carcinoma. A brief literature review of thyroid neoplasm in Graves disease is described.
TL;DR: It is concluded that PTU causes significant structural changes and stimulates its synthesis and secretion functions in the small intestinal epithelium.
Abstract: In this study, the effect of propylthiouracil on epithelial cells of the small intestine is examined by histological and cytological methods. As a result of histologic analyses an increase in PAS positive reaction was observed in the intestinal epithelium of the experimental group given PTU for 1 month. As a result of cytologic examination, administration of PTU for 1 month to rats induced marked ultrastructural changes in the small intestinal epithelium. As a result, we can conclude that PTU causes significant structural changes and stimulates its synthesis and secretion functions in the small intestinal epithelium
Journal Article•
TL;DR: Yougui pills can increase the reactive stress ability of lipid peroxidation in rats with hypothyroidism and has some effect in decreasing the free radical peroxidative damage in the body.
Abstract: [Objective] To investigate the mechanism of Yougui pills in lightening free radical peroxidative damage in rats with hypothyroidism. [Methods] Propylthiouracil intragastric dosage was adopted to result in experimental hypothyroidism in rat. Eight weeks later they were sacrificed and their blood was harvested to detect the function of thyroid gland and also the hepatocuprein (SOD) in blood serum. The thyroid gland tissue was obtained to determine the hepatocuprein (SOD) in it. [Results] The activity of SOD in hypothyroidism rats descended significantly. Yougui pills and the thyroid tablet up-regulated the activity of SOD significantly after treatment. The effectiveness of the thyroid tablet was better. Correlation analysis result displayed that the activity of SOD and T3, T4, FT3, FT4 were in significant positive correlation(P0.01). Negative correlation was fund between the activity of SOD and TSH (P0.05). But SOD in the glandular tissue of hypothyroidism rats was higher. Yougui pills and the thyroid tablet could improve the exorbitance of SOD to normal level. The effectiveness of Yougui pills was better. [Conclusions] Yougui pills can increase the reactive stress ability of lipid peroxidation in rats with hypothyroidism. It has some effect in decreasing the free radical peroxidation damage in the body.
Journal Article•
TL;DR: Propylthiouracil (PTU), a routine antithyroid drug, is used for the first time to induce a TSH rise in patients considered for radioiodine ablation of thyroid cancer to increase the chance of successful ablations with least possible cost.
Abstract: n patients with thyroid papillary carcinoma, performing an effective radioactive iodine ablation after total thyroidectomy requires adequate levels of serum thyrotropin. Administration of recombinant human thyroid stimulating hormone (rhTSH) is the current established method for patients with insufficient serum TSH levels four to six weeks after surgery and levothyroxine discontinuation. Two major problems with rhTSH are its cost and availability in most countries worldwide. We have used propylthiouracil (PTU), a routine antithyroid drug, for the first time to induce a TSH rise. Our patient was a 33-year-old woman with remnant thyroid tissue of 11. 5×4 mm after thyroidectomy. Her TSH was 12.7 /IU/ml, five weeks after surgery, and rose to 30. 0 /IU/ml after a 10 day trial of PTU. Radioiodine uptake index also increased from 28% to 56%. Radioiodine ablation was successfully done and patient showed no sign of recurrence or metastasis after 4 years. We propose that anti-thyroid drugs may be considered for post-operative induction of TSH rise in patients considered for radioiodine ablation of thyroid cancer. This may increase the chance of successful ablations with least possible cost.
Journal Article•
TL;DR: Thyroid function test results revealed that the patient was euthyroid within one month of starting treatment with propylthiouracil, and Thyroid scintigraphy confirmed the diagnosis of multinodular goiter.
Abstract: tectable on both initial and repeat tests, although T3 and T4 were not grossly elevated, consistent with the diagnosis of subclinical hyperthyroidism [TSH = 0.02 µU/ml (normal = 0.35–4.94 µU/ml); free T3 = 75 ng/dl (normal = 60–181 ng/dl); free T4 = 1.1 ng/dl (normal = 0.7–1.48 ng/dl)]. Thyroid ultrasonography indicated multinodular hyper/hypoechogenic nodules with a maximum nodule size of 1.24 x 1.04 cm. Thyroid scintigraphy confirmed the diagnosis of multinodular goiter. One nodule was hyperactive whereas other nodules were hypoactive as indicated by decreased global uptake of Tc-99m pertechnetate of the whole gland. After endocrine consultation, 300 mg/day propylthiouracyl was started. Within one month of starting treatment with propylthiouracil, control thyroid function test results revealed that she was euthyroid. The patient was discharged without any need for a pacemaker. Six months later, exercise test was normal and no arrhythmia was detected on holter monitor.
Dissertation•
01 Aug 2008
TL;DR: The chosen thyroid-responsive biomarkers were insufficient to consistently predict the presence of electrophysiological alterations and a severe reduction in serum total T4 concentration in developing pups was found to be a necessary condition for neurological impairment.
Abstract: From its influence on mitochondrial activity and basal metabolic rate to its complex interplay with other endocrine organs, the thyroid gland is vital for proper development and operation of the mammalian body. Neurological development is a special concern due to the relative sensitivity of gestating females and neonates to thyroid disruption. The studies described within investigate the effects of developmental exposure to antithyroid compounds on the neurodevelopment of rats. As peripheral tissues including the brain are capable of partial compensation in response to declining availability of thyroid hormones from serum, we hypothesized that measuring thyroid-responsive parameters such as tissue 5’-deiodinase enzyme activity thyroid hormone concentrations, and mRNA expression would provide data which would more closely correlate to neurological endpoints than serum thyroid hormone or thyrotropin (TSH) concentrations. We further hypothesized that younger animals would be more sensitive to thyroid disruption than older animals, due to diminished reserve of the compensatory mechanisms in the hypothalamic-pituitary-thyroid axis. We used two antithyroid compounds to test these hypotheses. Propylthiouracil (PTU) at 0, 0.3, 1, 3, and 10 ppm in drinking water, and perchlorate at 150ppm in drinking water were administered from gestational day 2 until weaning. Serum and cerebrocortical thyroid hormone concentrations were measured at postnatal days 4, 14, and 21-32, as well as in dams and pups allowed to recover for 60 days post-weaning. Hippocampal in vitro electrophysiological measurements were performed on pups and adults. Open field behavioral testing was performed on adults. Overall, we found that the chosen thyroid-responsive biomarkers were insufficient to consistently predict the presence of electrophysiological alterations. A severe reduction in serum total T4 concentration in developing pups was found to be a necessary condition for neurological impairment. Reductions in cortical T3 concentrations were not found to perfectly correlate with neurological outcomes. INDEX WORDS: Rat, propylthiouracil, thyroid, hippocampus, perchlorate, neurodevelopment, electrophysiology, deiodinase, triiodothyronine, thyroxine TISSUE BIOMARKERS OF THYROID STATUS AS CORRELATES OF NEURODEVELOPMENTAL IMPAIRMENT FOLLOWING GESTATIONAL AND LACTATIONAL EXPOSURE TO THYROID DISRUPTOR PROPYLTHIOURACIL