Effect of manganese on thyroid function in sheep

The effects of repeated doses of oral cholecystographic agents on serum thyroxine (T4), 3,3',5-triiodothyronine (T3), 3,3',5'-triiodothyronine (rT3) and thyrotrophin (TSH) concentrations were studied in 37 euthyroid male subjects. Iobenzamic acid, tyropanoic acid, iopanoic acid, and ipodate sodium, in a dosage of 3 g for 3 days, respectively, induced a significant decrease in serum T3 and an increase in rT3 within 24 h after the initial dose, followed by an increase in TSH and a slight increase in T4. The extent of the changes in rT3 varied between the agents, ipodate causing the greatest change, but without any relation to the changes in T3 or T4. Responses of serum T4, T3, rT3 and TSH concentrations to exogenous thyrotrophin-releasing hormone (TRH) and bovine TSH were also studied before and after 3-day doses of iopanoic acid. In 11 subjects given iopanoic acid, the response to TSH to TRH (500 micrograms, iv) was increased but the T3 response was unchanged. A dose of TSH (10 U.S.P. units, im) caused a significant increase in serum T3 and a decrease in TSH concentrations in 5 subjects both before and after cholecystography. It is thus suggested that in euthyroid subjects given multiple doses of oral cholecystographic agents, (1) the primary and consistent events are the reciprocal changes of serum T3 and RT3, although the extent of the changes is not coordinately reciprocal; (2) the responsiveness of the pituitary thyrotrophs and thyroid to TRH is preserved; and (3) the high basal and TRH-induced TSH in the serum may be ascribed to the decrease in the serum T3 concentration.

Thyroid function was studied in a large number of subjects residing in Varsi, a town in the province of Parma, Italy. In this area, endemic goiter associated with moderate iodine deficiency [59 +/- 3 (+/- SE) microgram iodine/g creatinine], as defined by WHO criteria, affects 65% of the population. Serum T4, T3, thyroglobulin (Tg), and TSH concentrations were measured by RIA in 1218 subjects. The TSH response to TRH was determined in 108 subjects selected randomly from the groups with different grades of goiter. No significant change in serum T4 concentrations was found in subjects with different grades of goiter. Serum T3 concentrations were higher in subjects with the larger goiters. Serum Tg concentration progressively increased, and serum TSH progressively decreased with increasing goiter size. The TSH response to TRH was diminished in subjects with larger goiters. The findings of decreasing serum TSH concentrations and blunted TSH responses to TRH as goiter size increased suggest the possibility of autonomous thyroid function in the larger goiters in subjects residing in this area of moderate iodine deficiency.

Adult rats who had neonatal hyperthyroidism (NH) have reduced BW and serum T4, T3, and TSH concentrations. Pituitary TSH responses to TRH administration under basal, T4-suppressed, and propylthiouracil-stimulated conditions suggest that the thyrotroph of these animals is more sensitive to the feedback effects of thyroid hormones. These studies were undertaken to examine, with the use of various thyroid hormone-responsive variables, thyroid status of adult NH rats. NH was induced by 12 daily sc injections of T4 (0.4 microgram/g BW) to neonatal male Sprague-Dawley rats. Adult NH and control rats were then studied at 120 days of age. Adult NH rats had significantly decreased mean BW (P less than 0.001), and serum T4 (P less than 0.005), T3 (P less than 0.001), and TSH (P less than 0.001) concentrations. The percent decreases were 12% for T4, 20% for T3, and 27% for TSH in adult NH rats. Mean pituitary GH concentration and hepatic alpha-glycerophosphate dehydrogenase and malic enzyme activities were significantly decreased in adult NH rats to 54% (P less than 0.005), 52% (P less than 0.025), and 39% (P less than 0.001), respectively, of control values. Mean pituitary TSH concentrations were similar in adult NH and control rats. Mean hepatic T4 5'-deiodinase activity of adult NH rats [200 +/- (SE) 23 fmol T3/min X mg protein] was significantly decreased to 56% of control levels (355 +/- 31 fmol T3/min . mg protein; P less than 0.005). Mean pituitary T4 5'-deiodinase activity of adult NH rats (32.8 +/- 3.3 fmol T3/min . mg protein) was significantly increased compared with that of control rats (21.2 +/- 1.7 fmol T3/min . mg protein; P less than 0.025). These changes are consistent with a hypothyroid state in adult NH rats. The observation of decreased serum TSH concentration and enhanced thyrotroph sensitivity to thyroid hormones in the face of increased pituitary T4 5'-deiodinase activity suggests that increased thyrotroph monodeiodination of T4 may be the central biochemical aberration responsible for the hypothyroid state in adult NH rats.

Serum thyroglobulin (Tg), T4, T3, FT4, FT3, TSH concentrations and TSH response to iv TRH (delta TSH) were measured in 56 consecutive patients with (multi) nodular goiter from a severely iodine-deficient endemic goiter area in Northeastern Sicily and in 11 non goitrous euthyroid individuals living in the same area. Serum Tg concentrations were sharply increased in goitrous subjects (453 +/- 476 ng/ml) and related to thyroid size and the presence of nodules (chi 2 = 43.5, p less than 0.0005). Serum TSH levels measured in goitrous patients (2.1 +/- 0.9 microU/ml) were significantly lower than those measured in nongoitrous iodine deficient subjects (3.1 +/- 0.9 microU/ml, p less than 0.001) and decreased with increasing goiter size and nodularity (chi 2 = 27.3, p less than 0.05). A similar pattern was shown by the analysis of the delta TSH (chi 2 = 43.1, p less than 0.0005). These results suggest that at least a part of the largest and multinodular goiters become autonomously functioning with duration and growing in size. In 13 goitrous patients with absent or impaired response to TRH, a significant direct relation was apparent between log-Tg and goiter size and nodularity (r = 0.64) with an inverse relationship between serum FT3 and delta TSH (r = 0.73). A computed program analysis based on the combination of different independent variables (x) including age, thyroid size and nodularity, serum TSH, log-Tg and FT3, indicated the existence of a significant negative relationship between these variables and the TSH response to TRH (r = 0.75, p = 0).(ABSTRACT TRUNCATED AT 250 WORDS)

T4-5'-monodeiodination in pituitary fragments and liver homogenates, serum thyroid hormones, an index of serum thyroid hormone protein binding, and serum TSH were measured in rats aged 2-72 days. Serum T4, T3, and TSH concentrations were lower in the 2-, 4-, and 9-day-old rats than in adult rats. The serum thyroid hormone-binding index was highest in neonatal rats, fell to a nadir at 21 days, and rose thereafter. The intrapituitary T4-5'-monodeiodination rate was 3.5 times the 72-day value in 2- and 4-day-old rats and fell to the 72-day value by 30 days of age. T4-5'-monodeiodination rates in liver homogenates were lower than the adult values in 2-, 4-, and 9-day-old rats, reaching the adult value in 21-day-old rats. When 5 mM dithiothreitol were included in the liver homogenate incubations, the absolute T4-5'-monodeiodination rates were increased, and the differences among 2-, 4-, 9-, 21-, and 72-day-old rats were abolished. Increased rates of intrapituitary T4-5'-monodeiodination may, in part, account for lower serum TSH concentrations in neonatal rats than in adults despite the lower serum T4 concentrations in the former. The differences between changes in pituitary and liver T4-5'-monodeiodination during maturation provide further evidence for local rather than systemic regulation of this reaction.

Male Sprague-Dawley rats were given graded doses of methylmercaptoimidazole (MMI), propylthiouracil (PTU), KClO4 or KI in drinking water for 4 days, or the lowest effective dose of each drug for various times. The rats were sacrificed at 1--2 p.m. and serum T3, T4 and TSH concentrations were measured by radioimmunoassays. It was found that administration of 5 mg/l of MMI, 10 mg/l of PTU and 100 mg/l of KClO4 for 4--14 days induced a transient rise in serum TSH and a fall in serum T3 or T4 or in both. The effects of KI were not consistent. In another series of experiments, PTU (10 mg/l) was given in drinking water for 4 days, and then graded doses of T3 or T4 were given iv, or 100 ng of TRH was injected into a tail vein, or the animals were exposed to 4 degrees C for 30 min. The initial high TSH levels were further increased by TRH and cold and decreased by T3 and T4. The PTU-treated animals had goitres after 4 days. We infer that low doses, that is to say 10--100 times lower than previously described, of antithyroid drugs induce a hypothyroidism characterized by an increased TSH level and a decreased serum T3 or T4 level or both. A 4 days' treatment with PTU (40 mg/l in tap water) is a suitable tool for studying the effect of various conditions on TSH secretion.

Effect of aging on thyroidal and pituitary T4-5′-deiodinase activity in female rats

The present study was carried out to evaluate the effectiveness of intramuscular administration of methyl-TRH, a potent analogue of thyrotropin-releasing hormone, for assessing pituitary reserve of TSH and prolactin and for distinguishing euthyroid, hypothyroid and hyperthyroid individuals. Serum samples were taken for 24 hours after intramuscular injection of methyl-TRH, 200 microgram, in 19 euthyroid subjects, 9 hypothyroid men and 9 hyperthyroid men. The mean serum prolactin and TSH concentrations were significantly elevated over baseline levels at 30 min in the euthyroid individuals and remained elevated for 3 to 4 hours. The serum TSH, T3 and T4 responses after intramuscular methyl-TRH in euthyroid subjects were clearly distinguishable from those of hyperthyroid and hypothyroid patients. Significant elevation of the serum T3 and T4 concentrations at 24 hours after intramuscular injection of methyl-TRH shows the sustained effect of this TRH analogue in euthyroid subjects.

Several studies have suggested that nausea and vomiting in early pregnancy are related to the levels of thyroid hormones and human chorionic gonadotropin (hCG). To ascertain this relationship, we investigated 60 pregnant women (30 subjects each with morning sickness and hyperemesis gravidarum) and compared them with 30 control subjects (by enzyme immunoassay method). Serum T3, T4 and TSH were determined in all the subjects while serum hCG was assayed in pregnant women only. Group comparison was done by applying Student's t-test and the relationship between various parameters was evaluated by calculating coefficient of correlation, "r". Serum T4 and hCG levels were significantly increased in hyperemesis gravidarum while TSH demonstrated a significant decline in the same group. Correlation analysis showed a direct relationship between serum T4 and hCG and an inverse relationship between serum TSH and hCG in pregnancy with morning sickness. Our results are suggestive of the involvement of these variables in the pathogenesis of morning sickness and hyperemesis gravidarum not only because their levels were significantly altered but the extent of increase or decrease in their level correlated well with the severity of symptoms in the study subjects.

Effects of Phenobarbital on Hypothalamic-Pituitary-Thyroid Axis in the Rat

Hypothalamic-pituitary-thyroidal axis alterations in bulimic patients

1. Serum levels of TSH, thyroxine (T4) and triiodothyronine (T3) have been measured during treatment and follow-up of patients with thyroid carcinoma. 2. Serum TSH and thyroid hormone levels were initially normal. Three weeks after total thyroidectomy, TSH was elevated in about 50% of patients and after a subsequent therapy dose of 131I it exceeded 30 mU/l in 90% of patients. Occasionally, TSH did not rise until after the second dose of 131I. Low serum T4 and T3 concentrations were associated with the increase of TSH. 3. Withdrawal of l-thyroxine replacement treatment in athyreotic patients for four weeks before test doses of 131I, led to falls of serum T4 and T3 concentration and a progressive rise of serum TSH after the first weeks but there was considerable variation in the final level reached. In the majority, values greater than 30 mU/l were attained despite some patients having received l-thyroxine for many years. A few patients on prolonged thyroxine maintenance had little or no increase in TSH despite considerable reduction in serum T4 and T3 concentrations. 4. The 131I concentration (muCi/g) developed in tumour tissue was also examined in relation to the serum TSH level. In general a tumour should not be considered as incapable of concentrating 131I adequately until serum TSH levels have exceeded 30 mU/l.

Reportedly, serum manganese concentrations increase after myocardial infarction, closely correlated with increased serum aspartate aminotransferase activity. However, these conclusions are apparently based on analyses of contaminated samples. Serum manganese concentrations after myocardial infarction have been re-investigated by neutron activation analysis, and no significant increase could be demonstrated. Because serum copper and zinc could be determined simultaneously, analyses for these trace elements are also reported, which confirm the findings of others. After myocardial infarction a statistically significant (0.02 smaller than P smaller than 0.05) increase in serum copper and a statistically significant (0.001 smaller than P smaller than 0.01) decrease in serum zinc were observed.

A total number of 103 fullterm (FT), 47 small-for-gestational age (SGA) and 35 preterm (PT) babies were studied from day 1–8 after birth. In FT a surge of TSH was invariably seen, followed by a decrease until normal adult levels were reached on day 2–4 after birth. Serum T4 and -T3, concentrations were higher than in adults, significantly correlated and decreased by 30 and 40% respectively from day 2 to 8 after delivery. In SGA the postnatal TSH hypersecretion was more variable. Serum T4 and -T3, concentrations were significantly correlated and lower than in FT. Serum T4 decreased insignificantly and serum T3 seemed to increase during the first week of life. In PT the postnatal TSH increase was highly variably. Serum T4 and -T3 were lower than in FT and did not change significantly during tne study period; serum T3 tended to increase. Birth weight as well as gestational age were correlated with the thyroid hormone concentrations. In babies with gestational age of more than 34–36 weeks normal serum T4 and T3 concentrations were often observed.It is concluded that the postnatal pituitary-thyroid hyperfunction may be subnormal in SGA and PT babies. If serum TSH concentration is not measured in screening for congenital hypothyroidism these babies may appear as false positives.

Serum T4, T3, rT3, free T4, free T3 and TSH were measured during and after normal pregnancy in 20 women. Special methodological precautions were taken to avoid interference of other hormones and protein alterations in the assays. Serum T4 and T3 were steadily increasing during the last part of the 1st trimester, and remained high and nearly stable during the 2nd and 3rd trimester of the gestation period. The high levels were approximately 1.5 times the values measured 10 weeks post-partum. Serum rT3 was elevated already during the last part of the 1st trimester and remained high throughout pregnancy, compared to the post-partum value. Serum free T4 and free T3 were slightly elevated in early pregnancy. The values decreased gradually during pregnancy and were slightly depressed during the 3rd trimester. A gradual increase in serum TSH was observed during pregnancy and the 2nd and 3rd trimester values were significantly higher than the post-partum value. The mean values for serum TSH, free T4 and free T3 remained always well within the normal range. Thus small variations in serum free iodothyronines and TSH occur during normal pregnancy, the alterations observed in the last trimester of the gestation period resembling those of a slight thyroid insufficiency. These trends in variation of the reference values are worth to remember in the diagnosis of borderline hypo- or hyperthyroidism and in the balanced treatment of pregnant women with thyroid dysfunction.