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Biomedical subjects

R Docter

Publications and source records attributed to R Docter.

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

Congenital hypothyroidism and partial thyroid hormone unresponsiveness of the pituitary in a patient with congenital thyroxine binding albumin elevation.

We describe a girl who presented at the age of 6 weeks with cardiogenic shock due to congenital hypothyroidism (serum thyroxine (T4) less than 12 nmol/l). Thyroxine replacement therapy was instituted. In spite of high total serum T4 levels, thyroid stimulating hormone (TSH) serum values remained elevated. The raised serum T4 levels were the result of congenital elevation of thyroid binding albumin (TBA). Toxic doses of both T4 and triiodothyronine (T3) normalized the elevated TSH levels indicating that the pituitary is responsive to thyroid hormone, albeit at a higher threshold. In patients with congenital TBA elevation and an altered T4 pituitary response requiring thyroid replacement therapy, the measurement of serum free T4 levels is the parameter of choice to monitor treatment.

Congenital Hypothyroidism↗
PubMed1989

Effects of propylthiouracil on the biliary clearance of thyroxine (T4) in rats: decreased excretion of 3,5,3'-triiodothyronine glucuronide and increased excretion of 3,3',5'-triiodothyronine glucuronide and T4 sulfate.

The liver metabolizes T4 by deiodination and conjugation to T4 glucuronide (T4G), but little information exists about the formation of T4 sulfate (T4S) in vivo. We have examined the excretion of T4G, T4S, T3 and rT3 glucuronide (T3G and rT3G) in bile, collected under pentobarbital anesthesia 0-8 h or 17-18 h after iv [125I]T4 injection to control and 6-propyl-2-thiouracil (PTU)-treated rats. Radioactivity in bile, plasma, feces, and urine was analyzed by Sephadex LH-20 chromatography and HPLC. PTU induced a 2-fold increase in the biliary excretion of total radioactivity (26.6% vs. 15.0% dose between 0-8 h; 2.0% vs. 1.0% dose between 17-18 h). Biliary metabolites, 17-18 h after T4 injection, in control vs. PTU rats amounted to (percent dose): T4G, 0.44 vs. 0.75; T3G, 0.19 vs. 0.07; rT3G, 0.02 vs. 0.15; and T4S, 0.06 vs. 0.32. Similar results were obtained for control rats when bile was collected between 7-8 h after iv T4. The excretion rate of T3G was lower and that of rT3G higher when bile was continuously collected for 8 h immediately after T4 administration, probably due to prolonged experimental stress. However, regardless of the period of bile collection, PTU induced a more than 24-fold decrease in the T3G/rT3G ratio and a 5-fold increase in T4S excretion. In the animals killed 18 h after T4 injection, PTU treatment increased plasma T4 retention by 50%, reduced urinary I- excretion by 74%, and increased fecal radioactivity by 47%. No conjugates were detected in feces, and the distribution of fecal T4:T3:rT3 was 70:18:2 in control and 68:7:6 in PTU-treated rats. The results indicate that 1) the glucuronidative clearance of T4 is not affected by PTU; 2) the T3G/rT3G ratio in bile is a sensitive indicator of type I deiodinase inhibition; 3) T4 undergoes significant sulfation in rats in vivo, and 4) biliary excretion of T4S is enhanced if its type I deiodination is inhibited.

Animals↗
PubMed1989

Hyperprealbuminemia, euthyroid hyperthyroxinemia, Zollinger-Ellison-like syndrome and hypercorticism in a pancreatic endocrine tumour.

Prealbumin, one of the main thyroxine transport proteins, has recently been shown to be a valuable immunohistochemical marker of neuroendocrine tumours. We report the case of a multisecretory pancreatic endocrine tumour whose prealbumin secretion was so high that it produced a peak on routine serum protein electrophoresis and induced a euthyroid hyperthyroxinemia. The maximal binding capacity of prealbumin for thyroxine was indeed markedly increased, whereas its affinity for this hormone was normal. The tumour was associated with gastric hyperacidity and hypergastrinemia thereby evoking a Zollinger-Ellison syndrome. The secretin stimulation test and gastrin tumoural immunohistochemistry were, however, negative. We suggest that the concomitant tumoural production of gastrin-releasing peptide was responsible for the gastric hyperacidity and hypergastrinemia. This hormone probably also accounted for a moderate hypercorticism.

Adrenocortical Hyperfunction↗
PubMed1988

Three-compartmental analysis of effects of D-propranolol on thyroid hormone kinetics.

Tracer thyroxine (T4), 3.3',5-triiodothyronine (T3), and 3,3',5'-triiodothyronine (rT3) kinetic studies were performed in normal T4 substituted subjects before and during oral D-propranolol treatment to determine whether changes in thyroid hormone metabolism in a propranolol-induced low-T3 syndrome result from inhibition of 5'-deiodination or inhibition of transport of iodothyronines into tissues. Data were analyzed according to a three-compartmental model of distribution and metabolism. T4 plasma appearance rate decreased by 16% (P less than 0.01), reflecting a decreased intestinal absorption of orally administered T4 during propranolol. Serum T4 and free T4 levels increased significantly by 14%, whereas T4 metabolic clearance rate (MCR) was lowered by 26% (P less than 0.001). No changes were observed in size of the three T4 compartments or in fractional and mass transfer rates of T4 from plasma to the rapidly (REP) and slowly (SEP) equilibrating pools. Serum T3, free T3, T3 plasma pool, T3 mass transfer rate to REP and SEP, and the T3 pool masses were all significantly decreased during propranolol to a similar extent as the T3 plasma production rate (PR). T3 MCR decreased by 14% (P less than 0.05). Serum total and free rT3 increased, whereas the rT3 MCR was substantially lowered during propranolol (P less than 0.001). The rT3 plasma pool, rT3 REP and SEP, and the mass transfer rates to REP and SEP increased, whereas no alterations were observed in rT3 PR and fractional transfer rates of rT3 to REP and SEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Causes and effects of the low T3 syndrome during caloric deprivation and non-thyroidal illness: an overview.

The increased serum reverse T3 and decreased T3 during caloric deprivation and non-thyroidal illness is caused by decreased T3 production (with intact degradation) and reversed T3 degradation (with intact production) respectively. These changes can ensue from two mechanisms i.e. decreased 5'D of T4 and of reverse T3 (possibly caused by a decrease in naturally occurring reducing agents) or by decreased transport of T4 and reverse T3 into the liver (possibly caused by decreased ATP concentrations in the liver). The effects of the low T3 syndrome at the tissue level are in many instances comparable to those seen in hypothyroidism. The effects lead to conservation of energy and decrease of protein breakdown. These effects are considered to constitute a beneficial adaptative mechanism in situations in which the organism is endangered. There is no evidence that treatment of patients with the low T3 syndrome with thyroid hormones is of any benefit. Knowledge at the present moment suggests that administration of thyroid hormones during caloric deprivation or non-thyroidal illness should be avoided.

Food Deprivation↗
PubMed1987

Cellular and humoral immunity in patients with hyperthyroid Graves' disease before, during and after antithyroid drug treatment.

Many reports of thyroid stimulating immunoglobulins (TSI) in relation to treatment of Graves' disease have been published and with variable results concerning prediction of permanent remission or relapse after therapy. A range of methods has been used and little has been published measuring TSI by using their ability to stimulate cyclic AMP production in human thyroid cells in monolayer culture. We therefore conducted a prospective study of the predictive value of such an assay in patients with hyperthyroid Graves' disease before, during and after treatment of one year with methimazole and thyroid hormone substitution. Furthermore, the possible relationship between activated suppressor T lymphocytes and TSI in patients followed before, during and after medical therapy has been studied. Patients were divided into two groups; group I, 15 patients, who stayed in remission and group II, 14, who relapsed during the first year after discontinuation of therapy. Mean TSI activity did not differ between the two groups before and during the first half year of medication. In the second half year of treatment, however, mean TSI activity was significantly lower in group I. TSI activity at the end of treatment appeared to have no value in predicting final outcome. Increased TSI activity in group II during treatment was reflected in an increased pertechnetate thyroidal uptake as compared to that in group I. There was no relationship between changes in TSI activity and T cell subsets (Leu 1, 2a, 3a). We found no difference in T lymphocytes between the two groups at any time during observation. Subsets of T lymphocytes in both patient groups did not differ from normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Active transport of iodothyronines into human cultured fibroblasts.

Thyroid hormone uptake into human cultured fibroblasts was studied using 2-min incubations with labeled iodothyronines. The results indicate the presence of an active T4 uptake process with two saturable sites with apparent Km values of 1.9 and 141 nM, respectively, and an active T3 uptake process with two saturable sites with Km values of 29 and 650 nM. The uptake of both hormones was energy dependent, i.e. inhibited by KCN or by incubation of the cells in the absence of glucose. By analogy with similar findings in rat hepatocytes we postulate that the high affinity systems represent active transport of thyroid hormone into the cell. Preincubation of the cells with 2 mM ouabain resulted in a decrease in the uptake of both T3 and T4, suggesting that a sodium gradient is necessary for transport. Similar to that in rat hepatocytes, uptake of T3 was inhibited by high concentrations of T4, and uptake of T4 was inhibited by high concentrations of T3. These data indicate that regulation of thyroid hormone uptake at the level of the plasma membrane may be operative in humans.

Biological Transport, Active↗
PubMed1987

Handling of iodothyronines by the liver and kidney in patients with chronic liver disease.

Possible arterio-venous gradients of T4, T3, rT3 and 3,3'-diiodothyronine (3,3'-T2) across the liver and the kidneys were measured in 9 patients with varying degrees of liver failure undergoing diagnostic catheterization. Plasma iodothyronine levels were measured in peripheral, hepatic and renal veins before and at 10-min intervals until 60 min after iv injection of 400 micrograms of TRH. In 2 patients estimated hepatic plasma flow and effective renal plasma flow were determined as well. In these 2 patients, no significant differences between iodothyronine levels in arterial and peripheral venous plasma were found. T4 and T3 levels were not significantly different between peripheral, renal and hepatic veins. Hepatic vein rT3 and 3,3'-T2 concentrations were 10.7 +/- 8.3% (mean +/- SD, P less than 0.005) and 36 +/- 18% (P less than 0.001) lower than those in the peripheral vein (N = 9). Renal vein rT3 was just (6.2 +/- 7.5%, P less than 0.05) lower than rT3 in peripheral vein, whereas 3,3'-T2 was not different between the two veins. Estimates of hepatic and renal plasma flow were in agreement with values from the literature. On the basis of these data approximate hepatic clearance rates of 110 and 380 1/day for rT3 and 3,3'-T2 and a renal clearance rate of about 35 1/day for rT3 were calculated. Sixty min after TRH, plasma T3 was increased to 147 +/- 56% (P less than 0.05) and 3,3'-T2 in peripheral plasma was increased to 142 +/- 36% (P less than 0.025), whereas plasma T4 and rT3 did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Inhibition of iodothyronine transport into rat liver cells by a monoclonal antibody.

The role of the rat liver plasma membrane in the regulation of uptake and subsequent deiodination of thyroxine (T4) or the biologically active thyroid hormone 3,3',5-triiodothyronine (T3) was investigated. Here we report on the production of monoclonal antibodies raised against rat hepatocytes. Two antibodies were selected. Antibody ER-22 did bind to a Mr 52,000 membrane protein and inhibited the 1- and 5-min uptake of both T4 and T3 by primary cultured rat hepatocytes in a dose-dependent fashion. As the uptake of T4 and T3 depends on the presence of a sodium gradient over the plasma membrane, the inhibitory potency of ER-22 on the Na+,K+-ATPase activity was investigated. No inhibition of the uptake of 86Rb+ could be determined, indicating that antibody ER-22 is not directed against the Na+,K+-ATPase but probably the carrier protein itself. Clearance of T3 from the medium and concomitant iodide production by cultured rat hepatocytes during a 20-h incubation in the presence of ER-22 were both inhibited by 50% with respect to a control incubation in the absence of monoclonal antibody, pointing to the importance of carrier-mediated transport in cellular uptake and metabolism of T3. A second monoclonal antibody did bind to two other plasma membrane proteins but did not inhibit transport of thyroid hormone.

Animals↗
PubMed1986

Thyroid-stimulating immunoglobulins and thyroid function tests in two siblings with neonatal thyrotoxicosis.

Thyroid function and serum TSI levels in two siblings with neonatal thyrotoxicosis are described. The first infant was treated with exchange transfusion and potassium iodide. The second infant was treated with intrauterine propylthiouracil followed by potassium iodide. In contrast to the first infant, the second infant had no clinical sign of neonatal thyrotoxicosis. He also had lower TSI levels with a biological half-life of 5 days. Only one of three assays showed some TSI activity in breast milk.

Adult↗
PubMed1986

Effects of caloric deprivation on thyroid hormone tissue uptake and generation of low-T3 syndrome.

Changes in thyroid hormone metabolism in the low-3,5,3'-triiodothyronine (T3) syndrome cannot be fully explained in all conditions by a decrease in 5'-deiodinase activity. Recent observations showed that in rat hepatocytes iodothyronines are taken up by an active transport mechanism. To investigate whether regulation, i.e., inhibition of active transmembraneous transport for iodothyronines in humans may contribute to the generation of the low-T3 syndrome, tracer thyroxine (T4) and T3 kinetic studies were performed in 10 obese subjects before and after 7 days on a 240 kcal diet. Kinetics analyses were performed according to a three-pool model of distribution and metabolism for both T4 and T3. For T4 kinetics, during caloric deprivation serum total T4 and plasma pool did not change and production rate and metabolic clearance rate (MCR) were significantly lower. Despite a significantly higher serum free T4, the mass transfer rate to the rapidly equilibrating pool (REP) and the slowly equilibrating pool (SEP) diminished significantly, leading to smaller tissue pools. For T3 kinetics, both serum total T3, free T3, plasma pool, and production rate diminished significantly, while MCR remained unchanged. Mass transfer rates to the REP and the SEP were lowered by approximately 50%, leading to smaller tissue pools. These changes cannot be fully explained by a similar decrease of serum free T3 (only 25%), indicating a diminished transport efficiency for T3. In conclusion, during caloric restriction, transport of T4 and T3 into tissues is diminished, and this phenomenon is much more pronounced for T4 than for T3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Carrier-mediated transport of thyroid hormone into rat hepatocytes is rate-limiting in total cellular uptake and metabolism.

We investigated if carrier-mediated transport into rat hepatocytes is rate-limiting in total cellular uptake and metabolism of thyroid hormone. Rat hepatocytes in primary monolayer culture were incubated under equilibrium conditions with tracer T4, T3 or rT3 in the absence or presence of inhibitors of thyroid hormone uptake, i.e., ouabain and ER-22, a monoclonal antibody against the rat hepatocyte plasma membrane. The results for all three iodothyronines show that inhibition of clearance from the medium during incubation is paralleled by a similar decrease in iodide production. This indicates that the decrease in metabolism of thyroid hormone is directly related to the inhibition of cellular uptake. These findings underline the potential importance of the plasma membrane in the regulation of thyroid hormone metabolism and, therefore, determination of expression of thyroid hormone activity.

Animals↗