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Biomedical subjects

A G Burger

Publications and source records attributed to A G Burger.

At least 55 records · Page 3Linked to original sources
PubMed1989

Glucoregulatory function of thyroid hormones: role of pancreatic hormones.

Glucose metabolism was investigated in humans before and 14 days after 300 micrograms L-thyroxine (T4)/day using a sequential clamp protocol during short-term somatostatin infusion (500 micrograms/h, 0-6 h) at euglycemia (0-2.5 h), at 165 mg/dl (2.5-6 h), and during insulin infusion (1.0 mU.kg-1.min-1, 4.5-6 h). T4 treatment increased plasma T4 (+96%) and 3,5,3'-triiodothyronine (T3, +50%), energy expenditure (+8%), glucose turnover (+32%), and glucose oxidation (Glucox +87%) but decreased thyroid-stimulating hormone (-96%) and nonoxidative glucose metabolism (Glucnonox, -30%) at unchanged lipid oxidation (Lipox). During somatostatin and euglycemia glucose production (Ra, -67%) and disposal (Rd, -28%) both decreased in euthyroid subjects but remained at -22% and -5%, respectively, after T4 treatment. Glucox (control, -20%; +T4, -25%) fell and Lipox increased (control, +42%; +T4, +45%) in both groups, whereas Glucnonox decreased before (-36%) but increased after T4 (+57%). During somatostatin infusion and hyperglycemia Rd (control, +144%; +T4, +84%) and Glucnonox (control, +326%; +T4, +233%) increased, whereas Glucox and Lipox remained unchanged. Insulin further increased Rd (+76%), Glucox (+155%), and Glucnonox (+50%) but decreased Ra (-43%) and Lipox (-43%). All these effects were enhanced by T4 (Rd, +38%; Glucox, +45%; Glucnonox, +35%; Ra, +40%; Lipox, +11%). Our data provide evidence that, in humans, T3 stimulates Ra and Rd, which is in part independent of pancreatic hormones.

Adult↗
PubMed1989

Pharmacokinetics of 3,5,3'-triiodothyroacetic acid and its effects on serum TSH levels.

3,5,3'-triiodothyroacetic acid is an effective inhibitor of TSH secretion in central hyperthyroidism. Serum, 3,5,3'-triiodothyroacetic acid was measured with an RIA preceded by immunoprecipitation. An anti-3,5,3'-triiodothyroacetic acid antibody was obtained in rabbits, using 3,5,3'-triiodothyroacetic acid coupled to hemocyanin and diazotized benzidine as antigen (cross-reactivity with T4, T3, tetraiodothyroacetic acid was 0.2, 1.1, and 5%, respectively). Endogenous 3,5,3'-triiodothyroacetic acid levels could not be detected in 14 euthyroid, 10 hypothyroid and 10 hyperthyroid sera (detection limit 0.055 nmol/l). Kinetic studies were performed in 6 healthy male subjects who received an oral and an iv dose of 1050 micrograms of 3,5,3'-triiodothyroacetic acid. The serum measurements were analysed according to a non-compartmental method. The half-life of 3,5,3'-triiodothyroacetic acid was 6 h 22 min +/- 29 min, the volume of distribution was 114 +/- 9 1/70 kg, and the plasma clearance rate was 298 +/- 141.(70 kg)-1.day-1. Highest 3,5,3'-triiodothyroacetic acid levels were measured after 40 min (for T3 2-3 h) and its absorption was 67 +/- 6%. The nadir of the mean TSH levels was 0.72 +/- 0.09 mU/l 6 h after 3,5,3'-triiodothyroacetic acid administration. However, the time course of serum TSH response did not differ from that obtained after administration of 37.5 micrograms T3. The dose-response effect for TSH was studied using oral doses of 350, 700, 1400 and 2800 micrograms 3,5,3'-triiodothyroacetic acid. TSH was measured 9 h after 3,5,3'-triiodothyroacetic acid administration at 17.00 h, and compared with control serum TSH levels obtained at 08.00 h (1.53 +/- 0.11) and at 17.00 h the day before the test (1.87 +/- 0.11). They were 1.05 +/- 0.15 (N = 9, mean +/- SEM), 0.83 +/- 0.08 (N = 24), 0.66 +/- 0.06 (N = 24), and 0.43 +/- 0.02 mU/l (N = 6), respectively. In conclusion, TSH inhibition by 3,5,3'-triiodothyroacetic acid is similar to T3, with a potency ratio of 1 to 18.

Administration, Oral↗
PubMed1988

Amiodarone alters thyroxine transfer and distribution in humans.

Previous studies indicate that increased serum total and free T4 levels may be secondary to a proportionally greater decrease in serum T4 clearance rates than in production rates after short-term amiodarone administration, to increased T4 production rates as well as reduced serum clearance rates in selective hyperthyroxinemia without overt hyperthyroidism following chronic amiodarone administration, and to a relatively greater increase in T4 production rates than in clearance rates in classical hyperthyroidism. To further evaluate amiodarone-induced alterations of T4 metabolism, serum T4 transfer and distribution were evaluated by compartmental analysis of T4 kinetic studies from eight normal subjects receiving short-term amiodarone or an equivalent amount of iodide, five patients with selective hyperthyroxinemia induced by chronic amiodarone therapy (n = 4) or ioxithalamic acid (n = 1), and five with classical hyperthyroidism. The model consisted of rapidly and slowly equilibrating pools exchanging with serum, with all losses occurring from the tissue pools. Short-term amiodarone administration reduced the fractional T4 transfer rates between serum and the rapidly equilibrating pool to 82% of baseline. In selective hyperthyroxinemia the fractional rates of T4 transfer between serum and both extravascular pools were increased sixfold, whereas minimal alterations were present in the hyperthyroid group. The serum equivalent volume of T4 distribution in the slow pool was significantly reduced following short-term amiodarone, whereas serum and rapid pool volumes were reduced in selective hyperthyroxinemia and slow pool volume was increased in hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effect of thyroid hormones on oxidative and nonoxidative glucose metabolism in humans.

The glucoregulatory function of thyroid hormones was investigated in six healthy subjects before and after 14 day 3,5,3',5'-tetraiodothyronine (T4) treatment (300 micrograms/day) using a sequential clamp protocol for 5 h at euglycemia (0-2 h) and hyperglycemia (165 mg/dl, 2-5 h) and different insulin infusion rates (1.0 for 0-3.5 h and 6.5 mU.kg-1.min-1, for 3.5-5 h). T4 treatment increased basal energy expenditure (+8%), glucose disposal (+31%), and oxidation (+87%) but decreased nonoxidative glucose metabolism (-30%) and was without effect on lipid oxidation. During the euglycemic clamp, T4 treatment enhanced insulin-induced glucose disposal (+16%), glucose oxidation (+34%), and inhibition of lipid oxidation (-66 vs. -40%); nonoxidative glucose metabolism was stimulated to a similar extent before and after T4. During hyperglycemia, 3,5,3'-triiodothyronine (T3) did not affect glucose disposal but increased carbohydrate-induced lipogenesis at both insulin infusion rates. We conclude that T4 treatment promotes glucose disposal and oxidation, T3 decreases noninsulin-mediated glucose storage but does not antagonize insulin action.

Adult↗
PubMed1988

Increased plasma clearance rate of thyroxine despite decreased 5'-monodeiodination: study with a peroxisome proliferator in the rat.

In euthyroid rats a 17-day treatment with nafenopin, a hypolipidemic agent and peroxisome proliferator, decreased serum total and free T4 concentrations to 32 +/- 5% and 62 +/- 8% (mean +/- SEM; n = 10), respectively, with no change in serum T3 and TSH concentrations. In methimazole-treated rats infused with 3 nmol T4/day/100 g BW, the nafenopin inhibitory effect was not significantly different from that in euthyroid rats. Nafenopin treatment had the following effects on peripheral T4 and T3 metabolism in euthyroid rats. The plasma clearance rate of T4 (PCR), which was measured by Alzet minipump infusion of tracer, was increased 2-fold (1.58 +/- 0.09 vs. 0.82 +/- 0.06 ml/h.100 g BW; P less than 0.001; n = 5), while the PCR of T3 was decreased (37.5 +/- 1.3 vs. 53.8 +/- 1.8; P less than 0.001; n = 5). The fecal clearance rate of radioactivity derived from T4 was increased 2-fold (1.93 +/- 0.10 vs. 0.77 +/- 0.07 ml/h.100 g BW), whereas the urinary clearance rate was not significantly modified. The 5'-deiodinase (5'D) activity, measured by deiodination of labeled rT3, was strongly inhibited in liver and kidney, not modified in brown fat and anterior pituitary, and increased in cerebral cortex. In methimazole-treated rats substituted with isopropyl-diiodothyronine only hepatic 5'D activity was decreased. It is concluded that the decrease in serum total and free T4, without alteration in serum T3 and TSH concentrations, resulting from nafenopin treatment is mainly due to changes in peripheral T4 and T3 metabolism, since it is also observed in T4-substituted animals. The increased PCR of T4 cannot be explained by an increase in deiodination activity, since the major 5'D pathways are inhibited after nafenopin treatment, and the urinary clearance rate is not modified. It can partly be explained by an increase in the fecal clearance rate of T4, which could be due to an increase in glucoronoconjugation. In addition, nafenopin was found to be a weak competitor of T4 binding to serum proteins, leading to a small increase in the free T4 fraction which might also contribute to the increased T4 PCR. The decrease in T3 PCR remains to be explained.

Adipose Tissue, Brown↗
PubMed1988

Human recombinant interleukin-1 beta decreases plasma thyroid hormone and thyroid stimulating hormone levels in rats.

Thyroid function was investigated in rats treated sc with a single injection of human recombinant interleukin-1 beta (hrIL-1). In 5 h 12.5 micrograms hrIL-1 decreased total serum T4 levels by 30 +/- 2% (P less than 0.01) and serum T3 levels by 35 +/- 4% (P less than 0.001). However free T4 and T3 fractions increased markedly within the first 140 min by 162 +/- 20% (P less than 0.001) and by 55 +/- 4% (P less than 0.001) resulting in a 88 +/- 20% increase in the free T4 concentration (P less than 0.001) but no increase in the free T3 concentration. Serum TSH concentration fell in the 5 h after the hrIL-1 injection by 77 +/- 3% (P less than 0.001). A similar decrease was observed with 0.125 micrograms hrIL-1. Five hours of starvation did not change serum TSH levels, suggesting that the effect of hrIL-1 on TSH was not due to decreased food intake. In order to test whether the decrease in serum TSH was due to an intrapituitary increase in T3, hrIL-1 was injected in hypothyroid rats: the fall of serum TSH was not prevented and it fell in 5 h from 14.05 +/- 0.56 to 9.66 +/- 0.98 ng/ml (31%, P less than 0.01, n = 14). These results suggest that hrIL-1 acts independently of thyroid hormones. Peripheral metabolism of T4 was studied by implanting [125I]T4 secreting minipumps during 14 days. There was no difference in T4 plasma clearance rate between control and treated animals. The fall of serum T4 was therefore explained by decreased secretion and not by increased catabolism since ether link cleavage of T4 and changes in hepatic deiodinase could not be detected. We therefore suggest that hrIL-1 inhibits thyroid function mainly at the hypothalamic-hypophyseal level.

Animals↗
PubMed1988

Decreased TSH response to TRH induced by amiodarone.

In order to test the reactivity of TSH to TRH during amiodarone treatment we investigated 7 hypothyroid subjects treated with 50 micrograms T3/day. A TRH test (200 micrograms iv) was performed before and after 6 weeks of treatment with 400 mg amiodarone/day. Amiodarone treatment induced a significant increase in serum total and free T3 (from 2.17 +/- 0.13 to 3.55 +/- 0.58 nmol/l and from 5.6 +/- 0.61 to 9.46 +/- 1.41 pmol/l). Basal TSH levels were significantly decreased and the maximal stimulation of TSH 20 min after TRH injection was only 20.0 +/- 3.3 mU/l during amiodarone treatment compared with 61.4 +/- 10.4 mU/l before treatment. These results indicate that in hypothyroid patients treated with amiodarone, the TSH response to TRH is blunted and that this is likely to be related to the higher total and free T3 levels or to a direct effect of amiodarone at the pituitary level.

Amiodarone↗
PubMed1987

[Diagnostic value of blood TSH levels in seriously ill patients].

Undetectable serum TSH values measured by immunoradiometric methods are highly suggestive of hyperthyroidism. However, serum TSH levels can also be very low in severely ill patients and in this case thyroid disease can be ruled out by thyroid hormone measurements. The authors have determined the frequency of low thyroid hormone values and of low serum TSH measurements in hospitalized patients. They investigated 276 euthyroid patients, 21 of whom were found to have decreased values for serum total T4 and free T4 index (FTI). Serum TSH was below the lower limit of detection (less than 0.2 mU/l) in 4 of these 21 patients (19%) and normal in 17 others. Serum TSH measurements are therefore considered more reliable than thyroid hormone measurements in ruling out primary hypothyroidism. Interestingly, serum TSH was also found to be unmeasurable in 7 of 248 patients with normal total serum T4 and FTI (3%). An unmeasurable TSH value is therefore not synonymous with low T4 in sick patients, which indicates that both measurements are needed in this category of patients. Data are also included on 7 patients with high serum total T4 and FTI but still normal serum T3, in whom as measurable serum TSH concentration rules out hyperthyroidism.

Acute Disease↗
PubMed1987

Effects of rifampicin on the peripheral turnover kinetics of thyroid hormones in mice and in men.

The induction of mixed function hepatic oxygenases by rifampicin is known to increase the metabolic clearance rate (MCR) of T4. By performing T3 and rT3 kinetics we have shown that rifampicin also increases the MCR of T3 and rT3. Using the fall of serum T4 during TSH suppression as an indirect marker of the production rate (PR) of T4, we have demonstrated that there was no major change in monodeiodination nor any shift to either 5'- or 5-monodeiodination. Rifampicin stimulates in mice the mixed function hepatic oxygenases. However, we were unable to increase hepatic deiodinase activity (deiodinase type I) in this species. It is therefore possible that the increased MCR of T4 in man is not mediated by an increased conversion rate either. As mixed function hepatic oxygenases are known to increase hepatic conjugation it is suggested that rifampicin increases the biliary excretion of iodothyronine conjugates.

Adult↗
PubMed1987

Brain cortex reverse triiodothyronine (rT3) and triiodothyronine concentrations under steady state infusions of thyroxine and rT3.

T4 and reverse T3 (rT3) can inhibit 5'-deiodinase type II activity in rat brain cortex, pituitary, and brown adipose tissue, raising the possibility that T4 may act in vivo after conversion to rT3. The aim of this study was to measure in hypothyroid (Tx) rats the content of brain cortex rT3 during a constant 7-day infusion of either [125I]T4 alone, corresponding to 12 pmol T4/day X 100 g body weight (BW), or together with 400 pmol T4/day. [125I]T4, rT3, and T3 were extracted from brain cortex, pituitary, kidney, and liver with a combination of adsorption chromatography on Sephadex G-25, HPLC, and immunoprecipitation. [131I]T4, T3, or rT3 were used as internal standards. [125I]rT3 could be detected in brain cortex, liver, and kidney in Tx rats infused with [125I]T4 (12 pmol T4/day X 100 g BW) and in those infused with 400 pmol T4/day X 100 g BW. The highest rT3 concentrations were found in brain cortex, where it represented 6% to 10.5% of the local T4 concentration. During an infusion of 400 pmol T4/day X 100 g BW, brain cortex T3 concentration was 6 times higher in the brain cortex than in serum, and even exceeded that of T4. In Tx rats receiving [125I]T4 alone the brain cortex to serum T3 ratio was 3:1, but the total serum T3 concentration, measured by RIA, was much higher than that due to conversion [0.50 +/- (SE) 0.1 pmol/ml vs. 0.018 +/- 0.002 pmol T3/ml], indicating thyroidal secretion. The effect of the blood-brain barrier on rT3 was measured by infusing [125I]rT3 over 4 days. After killing, rT3 was isolated as above. Approximately 3% of serum rT3 was retrieved from the brain cortex, whereas during the T4 infusion 40-50% of serum rT3 was found demonstrating that brain cortex rT3 is locally produced.

Animals↗
PubMed1987

Monodeiodination of triiodothyronine and reverse triiodothyronine during low and high calorie diets.

The impact of varying caloric intake on peripheral monodeiodination and plasma disposal of T3, rT3, and the three diiodothyronines (T2) was studied in five normal subjects while they were consuming a low calorie diet (1200 Cal/day) and again while receiving a high calorie diet (3600 Cal/day). Toward the end of each diet period 240 nmol 3,3'-T2 (126 micrograms) and 80 nmol 3',5'-T2 (42 micrograms) were infused for 7 h, and a bolus injection of 137 nmol 3,5-T2 (72 micrograms) was followed by a 12-h infusion of 69 nmol 3,5-T2 (36 micrograms) and 111 nmol rT3 (72 micrograms) on another day. [125I]T3 (30 muCi) was injected on the third day. The T2 and rT3 concentrations were measured by RIA during the 2 days of infusion, and the serum disappearance of [125I]T3 was studied by immunoprecipitation and trichloroacetic acid precipitation of the labeled T3. Four to 5% of the plasma disposal of T3 was accounted for by 3'-monodeiodination, and 36-39% by 5-monodeiodination. Increasing caloric intake resulted in a higher overall plasma disposal rate of T3, but no change in the percentage of T3 metabolized by monodeiodination pathways. In contrast, 5'-monodeiodination accounted for 21% of the total plasma disposal of rT3 during the low calorie diet and 45% during the high calorie intake. This increase in 5'-monodeiodination of rT3 was at the expense of alternative pathways of disposal. A marked increase in the plasma clearance rate of 3,5-T2 was also found during the high calorie diet, indicating that the level of caloric intake affects pathways of metabolism other than outer ring monodeiodination. These studies emphasize the important role played by diet in the regulation of peripheral thyroid hormone metabolism through modulating outer ring monodeiodination, and that overnutrition changes other pathways of iodothyronine metabolism as well.

Adult↗
PubMed1987

Interference of dimethyl alpha-(dimethoxyphosphinyl) p-chlorobenzyl phosphate (SR-202) in thyroid hormone metabolism: evidence of inhibition of monodeiodination.

SR-202 is a non-iodinated potential lipid-altering agent. When administered (100 mg) three times per day for 3 days to six euthyroid subjects it was associated with a 30 +/- 3% (mean +/- S.E.M.) fall in 3,3',5-triiodothyronine (T3) (P less than 0.001), a reciprocal 104 +/- 14% rise in 3,3',5'-tri-iodothyronine (reverse T3, rT3) (P less than 0.01), and a 37 +/- 7% rise in thyroxine (T4) (P less than 0.001). Basal and TRH-stimulated TSH did not change. These results suggested that SR-202 was acting as an inhibitor of the peripheral monodeiodination of T4 to T3. During a second study the same subjects received the same dose of SR-202 for a further 3 days following 15 days of progressive substitutive treatment with L-T4, which they continued to take at 200 micrograms/day until the end of the study. Despite higher levels of thyroid hormones in the substituted subjects, similar results were observed, serum T3 falling by 40 +/- 2% (P less than 0.001), serum rT3 and T4 rising by 168 +/- 24% (P less than 0.01) and 37 +/- 9% (P less than 0.01) respectively. These changes provide compelling evidence that SR-202 is an inhibitor of the peripheral conversion of T4 to T3 that acts on thyroid hormone metabolism without provoking a counter-regulatory pituitary response. It might prove to be a useful tool for the clinical investigation of thyroid function.

Organophosphorus Compounds↗
PubMed1986

[Euthyroid sick syndrome].

The "euthyroid sick syndrome", representing the changes of thyroid hormone metabolism in disease, embraces the following hormonal changes: 1) A decrease in serum T3 levels which is often accompanied by an increase in rT3 levels. Serum T4 levels remain normal. These changes are extremely frequent in many varied diseases. 2) In very severe disease, serum T4 levels may also decrease. The free T4 index is often decreased and the free T4 may either be normal or decreased. These changes reflect alterations of thyroid hormone metabolism and can be distinguished from primary hypothyroidism by a normal serum TSH level. 3) Occasionally there are transient increases of total and free T4. This disturbance of serum thyroid hormone levels is mostly due to drug interference with thyroid hormone metabolism (amiodarone etc.). Differentiation from hyperthyroidism is difficult. It is important to diagnose the "euthyroid sick syndrome" since this will avoid erroneous diagnosis and treatment or hypo- and hyperthyroidism.

Diagnosis, Differential↗
PubMed1986

Sensitivity of thyrotropin (TSH) secretion to 3,5,3'-triiodothyronine and TSH-releasing hormone in rat during starvation.

The mechanisms by which plasma T3 and TSH decrease after a 3-day starvation period are not completely understood. In this study we tested the hypothesis of a possible modification in the sensitivity of thyrotroph cell to T3 and/or TRH. For that purpose, TRH tests were performed before and after a 3-day starvation in euthyroid, thyroidectomized, and T3-treated (75 or 175 ng/100 g BW) thyroidectomized male Wistar rats. TRH (10 to 500 ng/100 g BW) was injected iv through a chronically-implanted catheter. In another set of experiments, hypophyseal TSH content was also determined. Our results showed that after a 3-day-starvation plasma TSH decreased in all except hypothyroid rats; TSH responsiveness to TRH was unchanged in euthyroid rats but was increased in hypothyroid rats; and the T3-dependent increase in TSH responsiveness to TRH was significantly amplified. Moreover, there was a significant positive correlation between TSH responsiveness to TRH and hypophyseal TSH content. These results suggest that starvation induces an increased sensitivity of thyrotroph cell to T3.

Animals↗