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Biomedical subjects

G Hennemann

Publications and source records attributed to G Hennemann.

At least 73 records · Page 4Linked to original sources
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

Pitfalls in the interpretation of thyroid function tests in old age and non-thyroidal illness.

In hyperthyroidism, measurement of the serum thyroxine (T4) index or free concentration often suffices to establish the diagnosis. In hyperthyroidism, including 3,3',5-triiodothyronine (T3) toxicosis, thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TRH) is blunted. Sensitive measurement of serum TSH may in the future be the first-line screening test not only for primary hypothyroidism but also for hyperthyroidism. In non-thyroidal illness serum T4, reverse T3 and T3 levels change in relation to severity of disease. In mild disease, T4 is initially increases as the severity of the non-thyroidal illness increases. Reverse T3 increases and serum T3 decreases when the patients become more ill. Serum TSH response to TRH is often blunted. In old age similar changes in serum iodothyronine concentrations may take place, probably related to existing non-thyroidal illness. Also many drugs may have different effects on serum parameters of thyroid function. In acute psychiatric diseases increased serum total and free T4 levels and a blunted TRH test may be encountered.

Aged↗
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

Place of radioactive iodine in treatment of thyrotoxicosis.

The effect of treatment of thyrotoxicosis with drugs, radioactive iodine, or surgery in different age groups is reviewed. In Graves' disease and toxic multinodular goitre the remission rate is about 40-50% after antithyroid drugs, but these drugs have little effect in toxic adenoma. Hypothyroidism developed in 35-49% of patients who had had thyroidectomy, and the risks of operation are high. The risk of malignant disease and genetic abnormalities was not significantly greater after treatment with radioactive iodine in any age group. In general, treatment with radioactive iodine should have priority over thyroidectomy at all ages.

Abnormalities, Drug-Induced↗
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↗
PubMed1986

Rapid and bacteria-dependent in vitro hydrolysis of iodothyronine-conjugates by intestinal contents of humans and rats.

Faecal suspensions from healthy humans, conventional (CV), germ-free (GF) and intestine-decontaminated (ID) rats were tested for the in vitro hydrolysis of 125I-labelled iodothyronine sulphates and 3,3',5-triiodothyronine glucuronide (T3G). Whereas 20-fold diluted human and CV rat faecal suspensions hydrolyzed up to 90% of the sulphates, no hydrolysis was observed in 5 times diluted faecal suspensions of GF and ID rats. These results add further weight to the assumption that intestinal iodothyronine sulphatase activity is of bacterial origin. Twenty times diluted human and CV rat faecal suspensions hydrolyzed approximately 80% of the T3G. In the 5 times diluted faecal suspensions of GF and ID rats up to 15% hydrolysis of T3G was still observed. It was concluded that the major part of the gastrointestinal iodothyronine glucuronidase activity is produced by bacteria. The remaining activity presumably originates from gastrointestinal mucosal cells.

Animals↗
PubMed1985

Radiotherapy of severe ophthalmic Graves' disease.

The effects of orbital irradiation on Ophthalmic Graves' Disease (OGD) were evaluated in 24 patients. All patients were irradiated after a median duration of eye symptoms of 12 months (range 3-36 months). Irradiation therapy was performed for loss of visual acuity, progressive diplopia and/or keratitis due to recent progression of eye symptoms. During a follow up period of 2-4.5 years, in 11 patients after irradiation, a mean decrease in proptosis oculi of 5.1 mm was found while 8 of these patients showed a mean increase in visual acuity of 0.26. Apparently, a decrease of activity of the inflammatory process in retrobulbar tissues can be achieved after irradiation, over a longer period of time in many patients. Furthermore concomitantly administered corticosteroids could be tapered off completely in all patients. Treatment of severe OGD of recent onset with irradiation, in combination with a short course of prednisone is very effective. This study also shows that prednisone treatment alone is not very successful because of the high recurrence rate of eye sings after decrease of the dose and the many side effects of the drug.

Adult↗