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Biomedical subjects

P Laurberg

Publications and source records attributed to P Laurberg.

At least 91 records · Page 5Linked to original sources
PubMed1987

Thyroxine and 3,5,3'-triiodothyronine content of thyroglobulin in thyroid needle aspirates in hyperthyroidism and hypothyroidism.

Thyroglobulin (Tg) was obtained by fine needle aspiration from patients with untreated hyperthyroidism due to Graves' disease and untreated hypothyroidism to determine whether alterations in its T4 and T3 content could account for the disproportionately high serum T3 compared to serum T4 found in both diseases. For comparison aspiration was performed from normal thyroid tissue in euthyroid patients operated for solitary thyroid lesions. The average amounts of Tg aspirated were: normal 177 +/- 52 (SE) micrograms, n = 7, hyperthyroidism 82 +/- 32 micrograms (n = 8); hypothyroidism 4.6 +/- 1.9 micrograms, n = 9. The iodothyronine content of Tg was, normal, T4 3.7 +/- 0.5 mol/mol, T3 0.28 +/- 0.04 mol/mol, T4/T3 13.7 +/- 1.4; hyperthyroidism, T4 3.8 +/- 1.0, T3 0.59 +/- 0.15, T4/T3 6.8 +/- 1.1; hypothyroidism, T4 3.3 +/- 0.5, T3 0.54 +/- 0.09, T4/T3 6.8 +/- 0.7. The iodine content of Tg was 28 +/- 3.1 atoms/mol in the euthyroid subjects and 31 +/- 7.3 atoms/mol in hyperthyroid patients. Hence, both untreated hyperthyroidism and untreated hypothyroidism were characterized by Tg with a normal T4 but a relatively high T3 content. This is probably related to the prolonged hyperstimulation of functioning follicular cells present in both diseases. The relatively high T3 content of Tg could not alone explain the relatively high T3 production compared to T4 production in these two thyroid diseases.

Adolescent↗
PubMed1987

Inhibitory effect of various radiographic contrast agents on secretion of thyroxine by the dog thyroid and on peripheral and thyroidal deiodination of thyroxine to tri-iodothyronine.

In previous studies we have found that the cholecystographic contrast agent ipodate induced a rapid, sustained and reversible inhibition of thyroxine (T4) secretion from perfused dog thyroid lobes. This type of inhibition of thyroid secretion has not been observed previously. To evaluate whether this effect is unique for ipodate, ten other iodine-containing radiographic contrast agents were tested. The four agents used for cholecystography (iocetamate, iodipamide, ioglycamate and iotroxate) all induced rapid inhibition of T4 secretion from TSH-stimulated perfused dog thyroid lobes, while none of six agents predominantly excreted through the kidneys (amidotrizoate, metrizamid, metrizoate, iodamide, diodone and ioxithalamate) influenced T4 secretion significantly. All the cholecystographic agents inhibited T4 deiodinases from dog thyroid and liver. Diodone also inhibited the deiodinases while none of the other compounds tested had any effect. The results indicate that the structure necessary to inhibit thyroid secretion is common to a number of cholecystographic agents and that it could be related to the structure responsible for the inhibitory effect of cholecystographic agents on T4 deiodinases.

Animals↗
PubMed1987

Cholecystokinin peptides as local modulators of thyroidal calcitonin secretion in the dog?

Cholecystokinin (CCK) is a heterogeneous gut hormone which is also synthetized in extra-intestinal endocrine cells and neurons. In order to examine the possibility that CCK peptides are local modulators of calcitonin secretion, we have studied the structure-activity relationship on calcitonin secretion from perfused canine thyroid lobes as well as the presence and molecular nature of CCK in the thyroid. Peptides containing the intact COOH-terminal tetrapeptide amide of CCK (CCK-4, CCK-5, pentagastrin, CCK-8 and gastrin-17) all induced dose-dependent (0.1, 3 and 100 nmol/l) increases in calcitonin release (P less than 0.05, n = 4) with biphasic secretion during 6-min infusion periods. The deamidated tetrapeptide and the COOH-terminal tripeptide were without effect. Gel chromatography of neutral water and acid-ethanol extracts of thyroid tissue, monitored by sequence-specific CCK and gastrin radioimmunoassays, disclosed a variety of CCK and gastrin peptides of which a predominant form resembled small molecular forms like CCK-4 and CCK-5. The presence in the thyroid of small CCK-like peptides and the pronounced effect of such peptides on calcitonin secretion suggest that calcitonin secretion is modulated by local release of small CCK peptides. They could originate from intrathyroidal nerves or from sub-populations of C-cells.

Animals↗
PubMed1987

A sensitive radio-immunoassay for serum thyroglobulin--including a correct screening for thyroglobulin autoantibodies.

A new thyroglobulin (Tg) assay employing polyethylene glycol (PEG) for separation of free and antibody bound [125I]Tg is described. By choosing a suitable PEG concentration the non-specific precipitation of free [125I]Tg was kept low while both [125I]Tg bound to rabbit anti-Tg immunoglobulins and to human Tg autoantibodies were precipitated. For all sera a 'blank' incubation with no rabbit anti-Tg immunoglobulins was run in parallel with the assay tubes. Hence any interference of Tg autoantibodies would be detected. A two-phase incubation gave a very low detection limit of 0.2 microgram/l. The inter-assay coefficient of variation was 9.4% and the intra-assay coefficient of variation was 5.6%. Dilution curves of normal sera were parallel to the standard curve and Tg standards added to normal sera were recovered quantitatively. Twelve out of 60 normal sera from the Randers area contained Tg autoantibodies. The average serum Tg in the 48 sera without antibody was 44.6 +/- 5.2 micrograms/l (SEM).

Adult↗
PubMed1986

VIP and hormone secretion from thyroidal follicular and C-cells.

The effect of vasoactive intestinal peptide (VIP) on the cAMP system of the thyroid and on the secretion of T4 and T3 from the follicular cells and calcitonin and somatostatin from the C-cells was studied in perfused dog thyroid lobes. Activation of the cAMP system was evaluated by measurements of the amount of cAMP released into the perfusion medium. T4, T3, calcitonin and somatostatin were measured by radioimmunoassays. 3 X 10(-6) M VIP induced increases in cAMP release and T4 and T3 secretion from the thyroid while there were no significant alterations in calcitonin and somatostatin release (n = 4). In experiments employing both of the two isolated thyroid lobes 100 microU/ml TSH gave considerably higher increases in T4 and T3 secretion than 10(-6) M VIP (n = 4). The effect of 10(-9) M VIP on T4 and T3 secretion was similar to that of 10(-6) M VIP (n = 4). 10(-10) M VIP induced a small but statistically significant increase in T4 and T3 secretion in two experiments while no effect was observed in two dogs. This high sensitivity of the follicular cells to VIP and the demonstration by others of VIP containing nerves in the thyroid suggest that VIP-ergic nerves may be involved in the regulation of thyroid hormone secretion.

Animals↗
PubMed1986

Thyroxine entering the thyroid gland via the vascular bed may leave the gland as triiodothyronines. Studies with perfused dog thyroid lobes.

In perfused dog thyroid lobes some of the T4 released from thyroglobulin (endogenous T4) is deiodinated during the secretion process to T3 and rT3, leading to a relative hypersecretion of triiodothyronines. The enzymes responsible for this deiodination are found in the follicular cells and resemble the T4 deiodinases in the liver. In the present study we investigated whether exogenous T4 infused into the thyroid via the vascular bed is also deiodinated to T3 and rT3. In two-sided thyroid perfusion experiments one lobe received T4 (200 ng/ml) during the perfusion period of 60-200 min. The contralateral lobe acted as control. T4 infusion was followed by a gradual increase in T3 and rT3 in thyroid effluent to a new level. This corresponded to 3.4 +/- 1.0% (mean +/- SE, n = 6) of the infused T4 leaving the gland as T3 and 0.7 +/- 0.2% as rT3. This thyroidal deiodination of exogenous T4 to T3 and rT3 was significantly reduced if T4 was infused in iodothyronine-free dog serum instead of buffer medium, probably owing to the presence of T4-binding proteins. Serum perfusion did not affect the deiodination of endogenous T4 to T3 significantly, whereas the deiodination of endogenous T4 to rT3 was depressed. Hence both endogenous T4 (from thyroglobulin) and exogenous T4 (arriving via the vascular bed) are deiodinated to triiodothyronines in the thyroid. Intrathyroidal T3 generation from plasma-borne T4 could be of considerable quantitative importance in patients with hyperstimulated goiters.

Animals↗
PubMed1986

Goitre size and outcome of medical treatment of Graves' disease.

One hundred and twenty-four patients with newly diagnosed hyperthyroidism received a combined thionamid-thyroxine medical therapy for approximately 2 years. According to the estimated goitre size before therapy and the type of goitre the patients were divided into 4 groups: Graves' disease no goitre (n = 19), Graves' disease small goitre (n = 57), Graves' disease medium or large goitre (n = 23), multinodular goitre (n = 25). The median follow-up period after cessation of medication was 64 (range 11-141) months. The remission rates in the different groups during follow-up were calculated using life table analysis. Graves' patients with no goitre or a small goitre had a significantly better outcome (remission % after 5 years 82.5 +/- 15.4 (SE) and 71.5 +/- 7.8, respectively) than Graves' patients with a medium size or large goitre (remission % after 5 years 37.0 +/- 11.1)(P less than 0.025). Most patients with multinodular goitre had a relapse within the first year after stop of medication (remission % after 5 years 15.5 +/- 10.1). Hence patients with Graves' disease having a small thyroid gland should be treated medically while surgery or radioiodine may be a more reasonable choice in Graves' patients with medium size or large goitres. Medically treated patients with toxic multinodular goitres have a very small chance of prolonged remission if medication is stopped.

Adult↗
PubMed1986

Fine needle aspiration in studies of thyroglobulin (Tg). Iodothyronine and iodine contents of Tg from patients with multinodular euthyroid goitre.

Fine needle aspiration from the thyroid gland was performed in 10 patients with multinodular euthyroid goitre. This was done to evaluate the possibility of obtaining sufficient quantities of thyroglobulin by this procedure to allow biochemical characterization. For comparison aspiration from normal thyroid tissue was performed in seven subjects during operation for solitary thyroid lesions (cancer or cysts). The total amount of Tg in aspirate was, goitre 666 +/- 171 micrograms (mean +/- SE), normal 177 +/- 52 micrograms; purified Tg contained, goitre vs. normal: iodine 9.1 +/- 2.2 vs. 26 +/- 3.9; T4 0.86 +/- 0.39 vs. 4.0 +/- 0.7; T3 0.080 +/- 0.024 vs. 0.28 +/- 0.06 mol/mol Tg (all significantly different), compatible with iodine deficiency pattern in Tg from the patients with goitre. Similar values were obtained if iodine and iodothyronines were measured in crude aspirate (after alkaline ashing and pronase hydrolysis, respectively) and related to the amount of Tg in aspirate measured by radioimmunoassay; thus avoiding the cumbersome purification of Tg. Hence fine needle aspiration of the thyroid can be used to obtain Tg for biochemical analyses. This considerably facilitates Tg studies in humans for clinical or investigative purposes.

Adult↗
PubMed1985

Cyclic AMP release from perfused dog thyroid lobes as a sensitive indicator of TSH activation of the secretion process. Evidence for two types of thyroid secretion latency.

It has been demonstrated in various types of thyroid tissue preparations that cyclic AMP (cAMP) released into the medium reflects the amount of cAMP in the cells. In the present study employing perfused dog thyroid lobes the dynamics of cAMP release were compared to those of thyroxine (T4) and triiodothyronine (T3) release. The experiments gave evidence that even the lowest concentrations of TSH which stimulate hormone release (in this study 1 microU/ml) also activate the cAMP system; the very high levels of cAMP obtained by stimulation with high concentrations of TSH (in this study 10,000 microU/ml) are not accompanied by corresponding high increases in hormone release. On the contrary the T4 and T3 release is lower than during stimulation with more moderate concentrations of TSH (100 microU/ml). Hence studies employing high concentrations of TSH and measurements of cAMP as indicator of activity of secretory processes should be interpreted very cautiously; the prolonged lag in thyroid hormone secretion observed after stimulation with low concentrations of TSH is accompanied by a corresponding lag in activation of the cAMP system. This pattern suggest that the duration of late secretory processes such as thyroglobulin pinocytosis and hydrolysis is independent of the degree of stimulation and not involved in the variations in secretion latency.

Animals↗
PubMed1985

Multisite inhibition by ipodate of iodothyronine secretion from perfused dog thyroid lobes.

Cholecystographic radiocontrast agents interfere with thyroid hormones in several ways. In the present study 1 mM ipodate induced a rapid sustained and reversible inhibition of the secretion of T4, T3, rT3, 3,3'-diiodothyronine, and 3',5'-diiodothyronine from perfused dog thyroid lobes. This effect was not reproduced by infusion of 3 mM iodide and not affected by 2 mM methimazol or 2 mM perchlorate. One millimolar of ipodate inhibited secretion of T4 to 23.7 +/- 2.8% of control (+/- SE, n = 6), 0.3 mM ipodate to 59.6 +/- 3.01 (n = 4), and 0.1 mM ipodate to 80.4 +/- 5.7% of control (n = 4). In search of the site of action in the thyroid of this inhibitory compound it was found that 1 mM ipodate inhibited TSH-induced increase in thyroidal cAMP, cAMP-induced generation of intracellular colloid droplets, and liberation of T4 and T3 from thyroglobulin by acid proteases and peptidases. These processes are those thought to be inhibited during iodide inhibition of thyroid secretion, via gradual formation of an unknown iodine-containing organic intermediate. It is suggested that the inhibition of thyroid secretion observed in the present study is due to structural similarities between ipodate and this putative iodine-containing mediator of the iodide-induced inhibition of thyroid secretion.

Animals↗
PubMed1985

A comparison of the effects of propylthiouracil and methimazol on circulating thyroid hormones and various measures of peripheral thyroid hormone effects in thyrotoxic patients.

Two groups of patients with newly diagnosed thyrotoxicosis were treated with propylthiouracil (PTU) 400 mg every 6 h for 4 days followed by methimazol (MMI) 40 mg every 6 h for 4 days or by MMI for 4 days followed by PTU for 4 days. The shift from MMI to PTU induced a considerable decrease in serum T3 while shift from PTU to MMI led to an increase in serum T3. Serum T4 decreased gradually during the whole treatment period. The opposite variations in serum T3 were accompanied by similar opposite variations in basal metabolic rate (BMR) (P less than 0.001). Hence the rapid variations in serum T3 which can be induced by PTU in thyrotoxic patients, are followed by rapid alterations in the thyrotoxic state as evaluated by BMR.

Achilles Tendon↗
PubMed1985

Thyrotrophin-releasing hormone (TRH) and hormone secretion from the follicular and C-cells of perfused dog thyroid lobes.

Recently we found small amounts of TRH immunoreactivity in the thyroid gland of dogs and pigs. In the present study we investigated if exogenous TRH influences the release of T4, T3 and cAMP from the follicular cells, and calcitonin and somatostatin from the C-cells of perfused dog thyroid lobes. 10(-5) mol/l TRH inhibited the TSH induced iodothyronine and cAMP release from the thyroid while 10(-8) mol/l TRH had no effect. The relative proportions of T4 and T3 in thyroid secretion were not altered by TRH infusion. TRH did not influence the basal or the Ca++ induced release of somatostatin and calcitonin. Hence TRH has a direct inhibitory effect on the hormone secretion from thyroidal follicular cells. This opens the possibility that TRH in the thyroid participate in the regulation of thyroid hormone secretion. Even though the concentration of TRH found to be effective is high our results may indicate that TRH in the thyroid participates in the regulation of thyroid hormone secretion as an antagonist to TSH.

Animals↗
PubMed1985

Evaluation of pituitary-adrenal function after pituitary surgery.

A short overnight metyrapone test and a 30-min ACTH test were performed in ten patients after pituitary surgery. At the initial testing 2 weeks after surgery the 30-min ACTH test was abnormal in two patients while normal increases in s-cortisol were observed in eight patients. These eight patients also had normal responses to ACTH when re-tested after 6-19 months. The short metyrapone test was a much more sensitive indicator of functional disturbances in pituitary/adrenal function. Two weeks after surgery the test was abnormal in seven of the patients. After 6-19 months some normalization of the short metyrapone test had occurred, probably due to disappearance of postoperative oedema and haematoma. However, the test was still abnormal in three patients having normal responses during the 30-min ACTH test. It is suggested that both tests are performed in such patients to specify a high risk group, i.e. both tests abnormal, and a low risk group with a normal 30-min ACTH test but subnormal responses during the short metyrapone test. This would be of help in the decision on cortisol supplementation and offer a high degree of safety for the patients.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Forskolin stimulation of thyroid secretion of T4 and T3.

Forskolin is a potent activator of adenylate cyclase in many tissues including the thyroid gland. We compared the effects of 10(-5) M forskolin and 100 mu units/ml TSH on the dynamics of T4 and T3 secretion from perfused dog thyroid lobes. Both agents induced pronounced increases in T4 and T3 secretion. The increase in secretion was significantly steeper during forskolin than during TSH stimulation. This may suggest that early processes such as TSH-receptor interaction and the subsequent activation of the catalytic unit of adenylate cyclase are of importance for the pattern of very gradual increase in hormone secretion during TSH stimulation of the thyroid. In other respects forskolin seems to induce absolute and relative secretion of T3 and T4 very similar to those obtained by cAMP and TSH.

Animals↗
PubMed1984

Propylthiouracil, ipodate, dexamethasone and periods of fasting induce different variations in serum rT3 in dogs.

Fasting or administration of propylthiouracil (PTU), ipodate, or dexamethasone are all known to induce a pattern of low serum triiodothyronine (T3) concentrations and high serum reverse T3 (rT3) concentrations in humans. In the present study it was found that this is not a universal phenomenon. In normal dogs exposed to fasting or these various pharmacologic agents, the serum T3 level was always depressed as in humans. However, different variations in serum rT3 levels were observed. Fasting and PTU administration were accompanied by slight decreases in the serum rT3 concentration. A single dose of ipodate did not alter serum rT3 levels, but serum thyroxine (T4) levels increased by more than 50%. Dexamethasone induced a considerable increase in serum rT3 levels, while serum T4 levels were unaltered. The results suggest that the high serum rT3 level nearly always seen in "the low T3 syndrome" in humans is merely a coincidental character of the human species, and that it has little importance for in vivo homeostasis.

Animals↗
PubMed1984

Mechanisms governing the relative proportions of thyroxine and 3,5,3'-triiodothyronine in thyroid secretion.

In subjects with normal thyroid function only a minor part of firculating 3,5,3'-triiodothyronine (T3) originates directly from the thyroid; the majority is produced in the peripheral tissues by deiodination of thyroxine (T4). However, T3 of thyroidal origin constitutes a relatively high fraction of the total T3 produced in many patients with thyroid hyperfunction or hypofunction. Such a relatively high T3 content in the secretion of the thyroid could be caused by a low T4/T3 ratio in thyroglobulin. Severe iodine deficiency is a well-known inducer of a low T4/T3 ratio, but a low T4/T3 ratio can also be produced independent of the iodine content. This is seen in in vitro studies of thyroglobulin iodination when small amounts of DIT are added to the incubation mixture and in vivo in TSH-treated animals and in patients with Graves' disease. Another mechanism for high thyroidal secretion of T3 could be an enhanced fractional deiodination of T4 to T3 in the thyroid. In vitro thyroid perfusion studies have shown that the T3 content of thyroid secretions is higher than would be expected from the T4/T3 ratio of thyroid hydrolysate and that the major mechanism is deiodination of T4 to T3. Thyroxine deiodinases are also present in the human thyroid, and the amount of T4 deiodinase is enhanced in the thyroids from patients with medically treated Graves' disease and in the hyperstimulated thyroids of rats. Other factors of possible importance for the mixture of T3 and T4 secreted by the thyroid are a relatively faster liberation of T3 than of T4 from thyroglobulin during partial hydrolysis (this faster release of T3 is probably the mechanism behind the more "rapid" secretion of T3 than of T4), or some kind of thyroid heterogeneity leading to pinocytosis and hydrolysis of thyroglobulin with a lower T4/T3 ratio than that of average thyroglobulin.

Animals↗
PubMed1984

Deiodination of T4 to T3 and rT3 by microsomes from normal human thyroid tissue.

An enzyme system capable of monodeiodinating T4 to T3 and to rT3 in a microsomal fraction of normal human thyroid tissue is characterized. The pH optimum for 5'-monodeiodination of T4 to T3 was around 7.0 The Km (apparent) for the conversion of T4 to T3 was 5.7 mumoles/l. PTU, ipodate and rT3 inhibited T4 deiodination to T3. The rT3 inhibition was of the partial competitive type. rT3 accumulation could not be detected at pH 7.4 or lower. At higher pH values rT3 could be measured in the incubates; however, the concentration was much lower than that of T3. The pH optimum was 9.0. Added rT3 disappeared rapidly at pH 7.4. The results suggest a high affinity of the 5'-deiodinase in human thyroid tissue for rT3, as has previously been described in the rat, but in contrast to our previous findings in dog thyroid and liver. Using tissue from 3 highly differentiated thyroid medullary carcinomas, deiodination could not be demonstrated, while it was normal using paraneoplastic thyroid tissue from the same patients. This suggests that the deiodinases studied originated from the follicular and not the C-cells of the thyroid.

Humans↗