Thyroid status and response to endothelin-1 in rat arterial vessels.
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We have previously reported that changes in thyroid status are associated with significant alterations in skeletal muscle blood flow during exercise and that changes in endothelium-dependent vasodilation may contribute to these blood flow abnormalities. The purpose of this study was to test the hypothesis that altered endothelium-dependent vasoconstriction is also associated with changes in thyroid status. To test this hypothesis, rats were rendered hypothyroid with propylthiouracil (Hypo, n = 14) or hyperthyroid with triiodothyronine (Hyper, n = 14) over approximately 3 mo. Treatment efficacy was confirmed by altered (P < 0.05) citrate synthase activity in several hindlimb skeletal muscles from Hypo and Hyper, compared with that in muscles from euthyroid rats (Eut, n = 12). Vascular rings were prepared from abdominal aortae, and responses to several vasoactive agents were determined in vitro. As found previously, maximal acetylcholine-induced vasorelaxation was modulated by thyroid status (Eut, 47 +/- 9; Hypo, 28 +/- 6; Hyper, 68 +/- 5%; P < 0.05). Contractile responses of vascular rings with intact endothelium to the endothelium-derived constrictor endothelin-1 (ET-1), however, were similar among groups across a range of ET-1 concentrations. In addition, maximal responses [Eut, 3.75 +/- 0.47; Hypo, 2.72 +/- 0.25; Hyper, 3.22 +/- 0.42 g; not significant (NS)] and sensitivities (Eut, 8.12 +/- 0.09; Hypo, 8.10 +/- 0.06; Hyper, 8.28 +/- 0.09 -log M; NS) to ET-1 were similar among groups. If these findings from the conduit-type abdominal aorta extend into resistance vasculature, it appears that changes in endothelium-dependent vasoconstriction do not contribute to skeletal muscle blood flow abnormalities associated with thyroid disease states. (+info)
Comparison of 99mTc-methoxyisobutyl isonitrile and 201T1 scintigraphy in visualization of suppressed thyroid tissue.
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Both (201)TI and (99m)Tc-methoxyisobutyl isonitrile (MIBI) have been used in the visualization of suppressed thyroid tissue in patients with autonomously functioning thyroid nodules (AFTNs). It has been suggested that thyroid-stimulating hormone (TSH) control is not a major determinant of both tracers. However, the mechanism of thyroid uptake of these agents is controversial. In this study, we compared (201)TI and MIBI in the visualization of suppressed thyroid tissue in patients with a solitary toxic AFTN. METHODS: Thirty-two patients (13 triiodothyronine [T3] and 19 T3 + levorotatory thyroxine [T4] hyperthyroid patients) with toxic AFTNs visualized on (99m)Tc-pertechnetate scanning were included in the study. All patients underwent MIBI and (201)TI thyroid scintigraphy within a 3-d interval. The scintigrams were analyzed both visually and semiquantitatively. For the semiquantitative analysis, regions of interest (ROIs) were generated over the nodule (N) and contralateral normal lobe (E), and the mean counts in each ROI were calculated. RESULTS: The N/E uptakes (mean +/- SD) for pertechnetate, MIBI, and (201)TI were 11.37 +/- 4.53, 4.76 +/- 1.38, and 1.63 +/- 0.15, respectively, in T3 + T4 hyperthyroid patients and 9.46 +/- 3.64, 2.73 +/- 0.63, and 1.57 +/- 0.23, respectively, in T3 hyperthyroid patients. Our results showed that (201)TI uptake of suppressed thyroid tissue compared with AFTN was more prominent and significantly higher than that of MIBI for both groups of patients (P = 1.08E-05 for T3 and 6.15E-09 for T3 + T4 hyperthyroidism). There was no significant difference for either pertechnetate or (201)TI (P > 0.05) when the N/E uptakes of both groups of patients were compared. However, the N/E uptake of MIBI in T3 + T4 hyperthyroid patients was significantly higher than that in T3 hyperthyroid patients (P = 6.69E-06). CONCLUSION: Clear visualization of suppressed thyroid tissue with both (201)TI and MIBI in patients with low serum concentrations of TSH suggests that TSH is not a major factor in the thyroid uptake of either agent. (201)TI is superior to MIBI in the visualization of suppressed thyroid tissue in patients with a toxic thyroid nodule. An increased rate of metabolism in the follicular cells of AFTNs in T3 + T4 hyperthyroid patients compared with that in T3 hyperthyroid patients might be responsible for the higher N/E for MIBI compared with that for (201)TI. (+info)
Effects of thyroid hormone on Leydig cell regeneration in the adult rat following ethane dimethane sulphonate treatment.
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We tested the effects of thyroid hormone on Leydig cell (LC) regeneration in the adult rat testis after ethane dimethyl sulphonate (EDS) treatment. Ninety-day-old, thyroid-intact (n = 96) and thyroidectomized (n = 5) male Sprague-Dawley rats were injected intraperitoneally (single injection) with EDS (75 mg/kg) to destroy LC. Thyroid-intact, EDS-treated rats were equally divided into three groups (n = 32 per group) and treated as follows: control (saline-injected), hypothyroid (provided 0.1% propyl thiouracil in drinking water), and hyperthyroid (received daily subcutaneous injections of tri-iodothyronine, 100 microg/kg). Testing was done at Days 2, 7, 14, and 21 for thyroid-intact rats and at Day 21 for thyroidectomized rats after the EDS treatment. Leydig cells were absent in control and hyperthyroid rats at Days 2, 7, and 14; in hypothyroid rats at all ages; and in thyroidectomized rats at Day 21. The LC number per testis in hyperthyroid rats was twice as those of controls at Day 21. 3beta-Hydroxysteroid dehydrogenase (LC marker) immunocytochemistry results agreed with these findings. Mesenchymal cell number per testis was similar in the three treatment groups of thyroid-intact rats on Days 2 and 7, but it was different on Days 14 and 21. The highest number was in the hypothyroid rats, and the lowest was in the hyperthyroid rats. Serum testosterone levels could be measured in control rats only on Day 21, were undetectable in hypothyroid rats at all stages, and were detected in hyperthyroid rats on Days 14 and 21. These levels in hyperthyroid rats were twofold greater than those of controls on Day 21. Serum androstenedione levels could be measured only in the hyperthyroid rats on Day 21. Testosterone and androstenedione levels in the incubation media showed similar patterns to those in serum, but with larger values. These findings indicate that hypothyroidism inhibits LC regeneration and hyperthyroidism results in accelerated differentiation of more mesenchymal cells into LC following the EDS treatment. The observations of the EDS-treated, thyroidectomized rats confirmed that the findings in hypothyroid rats were, indeed, due to the deficiency of thyroid hormone. (+info)
Serum digoxin in patients with thyroid disease.
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Serum digoxin concentrations were measured by radioimmunoassay in 17 hyperthyroid and 16 hypothyroid patients after a seven-day course of oral digoxin. The significantly higher levels of serum digoxin in patients with hypothyroidism and lower levels in those with hyperthyroidism were closely related to the measured changes of glomerular filtration rate and digoxin serum half time in these two groups. Differences in serum digoxin concentration contribute to the altered sensitivity to digoxin shown by patients with thyroid disease. (+info)
Genomic DNA analysis of thyrotropin receptor in a family with hereditary hyperthyroidism.
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Mutations of the thyrotropin receptor (TSH-R) gene have been reported in some cases of hyperthyroidism. We report a case of a family that had a high incidence of hyperthyroidism (6/13) which strongly suggested hereditary factors. We then analyzed whether the family had mutations of the TSH-R gene. No significant mutations in exon 10 of the TSH-R gene were found in the patient by restriction fragment length polymorphism analysis and polymerase chain reaction direct sequencing, when compared with those with 4 normal subjects and 2 patients with Graves' disease. Unknown mutations in the extracellular region of the receptor or other genes in this family remain to be studied. (+info)
Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.
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The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P<0.05) but not in the slow-twitch muscle (the soleus). PDK4 protein expression was increased by experimental hyperthyroidism in both muscle types, there being a greater response in the anterior tibialis (4.2-fold increase; P<0.05) than in the soleus (3.2-fold increase; P<0.05). The hyperthyroidism-associated up-regulation of PDK4 expression was observed in conjunction with suppression of skeletal-muscle PDC activity, but not suppression of glucose uptake/phosphorylation, as measured in vivo in conscious unrestrained rats (using the 2-[(3)H]deoxyglucose technique). We propose that increased PDK isoform expression contributes to the pathology of hyperthyroidism and to PDC inactivation by facilitating the operation of the glucose --> lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle. (+info)
Vasoactive intestinal polypeptide in rat heart atria: the effect of hyperthyroidism.
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The effects of transient and sustained hyperthyroidism on vasoactive intestinal polypeptide-like immunoreactivity (VIP-LI) levels were studied in the heart atria of developing and adult rats. Newborn rats were divided into 5 groups. Neo-T animals were treated with thyroxine (T4) during postnatal days 1-8 and sacrificed at the age of 60 days. Neo-S rats were treated with T4 during postnatal days 1-60 and sacrificed one day later. Adult-1 and Adult-2 animals received T4 during days 52-60 and were sacrificed 5-6 days and 1 day later, respectively. Control animals were injected with saline. VIP-LI concentrations were determined in extracts from the left and right atria separately. In Neo-S and Adult-2 rats, spontaneous heart rate, the weight of both atria and total T4 serum levels were significantly enhanced, while their body weight was decreased. The ratio atria weight to body weight was significantly increased in all groups except for Adult-1 animals. Hyperthyroidism led to a significant decrease in VIP-LI levels in both atria of Neo-S and Neo-T rats. Hyperthyroidism induced in adult rats also decreased VIP-LI levels in both atria. However, this change was only transient. In conclusion, our data have provided new evidence that hyperthyroidism induced during the early neonatal period interferes with the development of VIP-ergic innervation in rat atria. The period of the first few postnatal days seems to be essential for this effect, since VIP-LI concentrations in 60-day-old animals did not significantly differ between Neo-S and Neo-T atria. (+info)
Prevalence of thyroid disease, thyroid dysfunction and thyroid peroxidase antibodies in a large, unselected population. The Health Study of Nord-Trondelag (HUNT).
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OBJECTIVE: To examine the prevalence of thyroid disease and dysfunction including thyroid autoimmunity in Norway. MATERIALS AND METHODS: All inhabitants 20 years and older (94009) in Nord-Trondelag were invited to participate in a health survey with a questionnaire and blood samples. RESULTS: The prevalence of former diagnosed hyperthyroidism was 2.5% in females and 0.6% in males, hypothyroidism 4.8% and 0.9%, and goitre 2.9% and 0.4% respectively. In both sexes the prevalence increased with age. In individuals without a history of thyroid disease the median, 2.5 and 97.5 percentiles for TSH (mU/l) were 1.80 and 0.49-5.70 for females and 1. 50 and 0.56-4.60 for males. The TSH values increased with age. When excluding individuals with positive thyroid peroxidase antibodies (TPOAb) (>200U/ml), the 97.5 percentiles dropped to 3.60 mU/l and 3. 40 mU/l respectively. The prevalence of pathological TSH values in females and males were TSH >/=10mU/l 0.90% and 0.37%; TSH 4.1-9. 9mU/l 5.1% and 3.7%; and TSH200U/ml) was 13.9% in females and 2.8% in males. In females the lowest percentage (7.9%) of positive TPOAb was seen with TSH 0.2-1.9mU/l and increased both with lower and higher levels of TSH. The percentage of males with positive TPOAb was lower than in females in all TSH groups except for those with TSH>10mU/l (85% TPOAb positive). CONCLUSIONS: In spite of a high prevalence of recognised thyroid disease in the population a considerable number of inhabitants have undiagnosed thyroid dysfunction and also positive TPOAb. (+info)