Effect of triiodothyronine administration on reduced expression of type 1 iodothyronine deiodinase messenger ribonucleic acid in streptozotocin-induced diabetic rats.
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To examine the mechanism behind a decrease in type 1 iodothyronine deiodinase (D1) gene expression in diabetes mellitus, we evaluated the effect of administering T3 and/or insulin on D1 activity and the mRNA levels in the liver of streptozotocin (STZ)-induced diabetic rats. STZ (100 mg/kg BW) was administered to male Wistar rats, and the rats were divided into four groups as follows: (1) STZ alone, (2) STZ and T3 (5 microg/100 g BW daily for 7 days), (3) STZ and insulin (intermediate-acting insulin, 4 units/100 g BW daily for 7 days), and (4) STZ, T3, and insulin. Blood glucose levels increased in Group 1, but were normalized in Group 3. Serum T3 levels were markedly decreased in Group 1. They were within normal limits 24 hours after the last administration of T3 in Group 2 and after the administration of insulin in Group 3. T3 levels were supranormal in Group 4. TSH levels were normal in Groups 1 and 3, but were suppressed in Groups 2 and 4, suggesting that rats in Groups 2 and 4 were actually in a hyperthyroid state after injecting a large amount of T3. D1 activity in Group 1 was reduced significantly, but it was normal in Groups 2 and 3, and increased in Group 4. D1 mRNA levels in the liver in Group 1 decreased significantly, but they were increased to within normal limits by adding insulin in Group 3. They were also normal in Group 2 where hyperglycemia was evident and rats were hyperthyroid after administering T3. D1 mRNA in Group 4 increased significantly where glucose levels were normal and T3 levels were increased. We suggest that the decrease in hepatic D1 mRNA in STZ-induced diabetic rats is due to metabolic derangement caused by insulin deficiency in addition to a possible decrease in tissue T3 availability. (+info)
Clinical characteristics of amiodarone-induced thyrotoxicosis and hypothyroidism in Japan.
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Since amiodarone was introduced in Japan in 1992, the incidence of the drug-induced thyroid dysfunction has been increasing. We studied the thyroid function of 13 patients with amiodarone-induced thyrotoxicosis (AIT) and 11 patients with amiodarone-associated hypothyroidism (AAH) who had been referred to our Institute in the last 6 years. AIT and AAH developed after 39+/-21 and 20+/-16 months of amiodarone treatment, respectively. One patient developed AAH followed by AIT. The AIT ranged from subclinical to overt thyrotoxicosis. Four patients with moderate to marked AIT were treated with methimazole. Their thyrotoxicosis persisted for 3 to 9 months, despite administration of antithyroid agents. One patient with mild thyrotoxicosis was treated with prednisolone, resulting in a euthyroid state in a few months. Eight patients with asymptomatic to moderate thyrotoxicosis resolved spontaneously without any treatment. In four asymptomatic patients with AIT, serum levels of T3 and T4 were in the upper normal range or slightly high (< 12 microg/dl), accompanied by suppressed TSH (<0.1 microU/ml) and high thyroglobulin levels, suggesting destruction-induced thyrotoxicosis. Such a subclinical thyrotoxicosis developed repeatedly in one patient. Ultrasonographic studies revealed no nodular lesion in the thyroid, and color flow Doppler sonography demonstrated no hypervascularity in the thyroid gland in any AIT patient. Although it is postulated in Europe that there are two types of AIT, namely type I, which develops in patients with latent Graves' disease or toxic multinodular goiter, and type II, which develops in an apparently normal thyroid as destructive thyroiditis, all AIT patients we have seen so far had developed destructive type AIT. Sufficient intake of iodide and a very low incidence of toxic multinodular goiter may account for the rare incidence of type I AIT in our country. Mild to moderate AIT resolved spontaneously without discontinuing amiodarone, but it was discontinued in two of 13 AIT patients because of extrathyroidal adverse reactions. (+info)
Superovulation of immature hypothyroid rdw rats by thyroxine therapy and the development of eggs after in vitro fertilization.
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The aim of this study was to examine the effect of thyroxine on ovulation in immature rdw rats and the fertilization and development of the eggs. Serum thyroxine concentrations at 30 days of age were significantly lower in rdw rats than in normal rats (P < 0.001), and greatly increased after thyroxine replacement therapy (P < 0.001). Although few eggs (1-5 +/- 1-2) were obtained from immature rdw rats treated with gonadotrophins alone, females treated with gonadotrophins and thyroxine ovulated significantly more eggs (85 +/- 5). As a control, normal littermates ovulated 21-45 eggs when treated with gonadotrophins alone, and 68 eggs when administered with gonadotrophins and thyroxine. Of the eggs collected from rdw rats treated with gonadotrophins and thyroxine, and inseminated with spermatozoa from mature F1 males, 98% were penetrated and in almost all (99%) of these eggs, male and female pronuclei formed. Forty-seven per cent of the pronuclear eggs developed to the blastocyst stage in vitro. After transfer to recipients, 21% (14/66) of one-cell and 22% (8/37) of two-cell embryos developed to offspring, and 62% (8/13) of pups were of rdw/rdw genotype. The average body weight (6.9 versus 7.8 g) of offspring derived from one-cell embryos was lower than that for two-cell embryos. The morulae and blastocysts did not develop to term, although 41% implanted in the uterine horns of recipients. In conclusion, in immature rdw rats, superovulation was induced by gonadotrophins combined with thyroxine therapy and the superovulated oocytes were fertilized and developed in vitro and developed to term after embryo transfer. (+info)
Effects of induced hypothyroidism on ovarian response to superovulation in Brahman (Bos indicus) cows.
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To evaluate the effects of hypothyroidism on ovarian function, multiparous, nonlactating Brahman cows (n = 18) were assigned randomly to dietary treatments containing either 0 (C; n = 9) or 4 mg x kg BW(-1) x d(-1) 6-n-propyl-2-thiouracil (PTU; n = 9), to suppress thyroid function, in the feed concentrate. Weekly changes in BW and body condition score (BCS) were recorded. Dietary treatments began on d 10 of the estrous cycle. Ten days after the first treatment estrus, all cows received daily i.m. injections of 25 IU of porcine FSH over a 3-d period. Seven days after AI, embryos were collected nonsurgically, and the ovaries were removed via midflank laparotomy. Based on thyroxine (T4) concentrations after 49 d of treatment, five cows were hypothyroid (H-PTU) and four were partially suppressed (P-PTU). Cows in the PTU group had greater (P<.01) ADG, (P<.05) ovarian weights, and numbers of large (> or =8 mm) (P<.05) follicles. Cows in the PTU group had lower embryo recovery rate (P<.001), fertilization rate (P<.001), and percentage of blastocysts (P<.1) than C cows. The H-PTU cows had greater numbers of luteinized follicles (P<.06), greater concentrations of progesterone (P4) in the follicular fluid at all size categories (P<.1), and greater numbers of corpora lutea (P<.05) than C cows. The ratio of luteal to serum P4 on d 7 was greater (P<.05) in hypothyroid cows. Induced hypothyroidism improved weight gain and BCS, increased ovarian response to FSH, and affected ovulation, fertility, and P4 secretion in superovulated Brahman cows. (+info)
Response to thyrotrophin-releasing hormone in atrial dysrhythmias.
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Seventy-eight clinically euthyroid patients with atrial dysrhythmias, either established or paroxysmal, and sixty-three patients in sinus rhythm with coronary disease were screened for hyperthyroidism using thyroid function tests including the thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH). All had normal levels of serum thyroxine (T4) apart from three with dysrhythmias who were found to have hyperthyroidism. Twenty per cent of patients with atrial dysrhythmias and 10% of those in sinus rhythm had exaggerated TSH response to TRH. Thirty-six per cent of patients with an exaggerated response of TSH to TRH had significant titres of thyroid auto-antibodies compared with 15% with positive antibodies in those with normal TSH response to TRH. Auto-immune thyroid disease may be more closely related to heart disease than has previously been recognized. Rapid atrial dysrhythmias may occur in the presence of a normal serum thyroxine, high levels of TSH and positive thyroid antibodies. (+info)
Urinary iodine concentrations and thyroid function in adult Zimbabweans during a period of transition in iodine status.
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BACKGROUND: In 1993 the compulsory iodization of salt was introduced in Zimbabwe, a country that was previously an area of severe iodine deficiency. OBJECTIVE: The objective of this study was to document urinary iodine excretion and biochemical thyroid function in seemingly healthy, community-dwelling adults after the introduction of iodization. DESIGN: A multistage, random sampling method was used in rural and urban settings to identify households from which the senior household member (aged >35 y) was recruited (alternating male and female recruits). Demographic data were collected for each subject and urinary and venous blood samples were taken. Urinary iodine excretion and serum thyroid hormone status (thyrotropin and total thyroxin) were evaluated according to age, sex, and area of residence. RESULTS: A total of 736 adults were recruited (253 men; mean age: 64 y). Urinary iodine concentrations were high [median (first and third quartiles): 4.41 (2.84, 6.78) micromol/L, or 560 (360, 860) microgram/L] and were significantly higher in rural areas than in urban areas [4.73 (3.07, 7.14) micromol/L, or 600 (390, 906) microgram/L, compared with 3.47 (2.05, 4.73) micromol/L, or 440 (260, 600) microgram/L; P < 0.001]. Urinary iodine excretion declined significantly with increasing age (r = -0.29, P < 0.001). Serum thyroid status suggested that the prevalence of biochemical hyperthyroidism in the study was 3%, with 13 of 415 cases in rural and 3 of 149 cases in urban subjects. CONCLUSION: This study reaffirms the need to continuously monitor iodine replacement programs to ensure efficacy. (+info)
An estimation of selenium requirements for New Zealanders.
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BACKGROUND: Current US dietary recommendations for selenium are based on maximization of plasma glutathione peroxidase (GSHPx) activity according to data from one study of Chinese men. OBJECTIVE: The effect of various amounts of supplemental selenium on GSHPx activities in blood of New Zealand adults was investigated to calculate a selenium requirement for New Zealanders. The effect on plasma selenoprotein P and thyroid hormones was also investigated. DESIGN: Fifty-two adults with low blood selenium concentrations ingested a placebo or 10, 20, 30, or 40 microgram Se as L-selenomethionine daily for 20 wk. RESULTS: Plasma and whole-blood GSHPx activities increased in all supplemented groups but reached a plateau only in the group receiving 40 microgram Se, as determined by statistical analysis. Increases in selenoprotein P were greater than those for selenium and GSHPx at all supplement intakes. Thyroxine concentrations decreased in supplemented groups but the decrease was significantly different from that in the control group only for the 10-microgram group and for all supplemented groups combined. CONCLUSIONS: An upper estimated requirement of 90 microgram Se/d was calculated as the intake necessary for maximization of plasma GSHPx activity, as used in the derivation of the US recommended daily allowance. Our lower estimated requirement of 39 microgram Se/d was the intake necessary to reach two-thirds of maximal GSHPx activity, as was used in calculating the World Health Organization normative requirement. The lower estimate is a realistic goal for New Zealand but the upper estimate could be achieved only with regular inclusion of high-selenium foods. (+info)
Circannual changes in free thyroxine, prolactin, testes, and relative food intake in woodchucks, Marmota monax.
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Woodchucks (n = 12-14/group) with circannual cycles entrained to northern versus southern hemisphere photoperiods were assessed monthly for 16 mo. Changes in serum total triiodothyronine (TT(3)), free thyroxine (T(4)), total thyroxine (TT(4)), and prolactin were determined in a subset of five animals per group. Metabolic hormone results were examined in relation to changes in body weight, food intake, and serum testosterone (n = 12-14/group). Seasonal changes in each parameter were similar in both groups as were nadir and peak TT(3) (162 +/- 6 and 392 +/- 12 ng/ml, respectively), free T(4) (19 +/- 2 and 86 +/- 7 ng/ml, repectively), TT(4) (3.2 +/- 0.2 and 8.0 +/- 0.5 ng/ml, respectively), and prolactin (0.6 +/- 0.1 and 14 +/- 2 ng/ml, respectively). In late winter and early spring, simultaneous increases in both free T(4) and prolactin were associated with 1) a large increase in food intake, 2) a decline in body weight to nadir values, 3) a corresponding negative energy balance, 4) a peak and decline in serum testosterone, and 5) a modest increase in TT(4) and large decline in serum TT(3). Low levels of free T(4) and prolactin were observed in summer when energy balance was very positive. The results demonstrate that, in woodchucks, serum T(4) and prolactin undergo seasonal changes during annual cycles entrained by photoperiod. The results suggest that changes in free T(4), acting as a calorigenic hormone, and changes in both T(4) and prolactin, potentially acting as lipolytic, antilipogenic, and/or orectic hormones, are likely involved in the mechanisms underlying the corresponding seasonal changes in food intake, fat metabolism, and energy balance in this species. Their potential roles in gonadal regression and recrudescence are less clear. (+info)