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Biomedical subjects

P Laurberg

Publications and source records attributed to P Laurberg.

At least 19 recordsLinked to original sources
PubMed1992

Radioiodine treatment of recurrent hyperthyroidism in patients previously treated for Graves' disease by subtotal thyroidectomy.

Radioiodine therapy is often employed for treatment of patients with relapse of hyperthyroidism due to Graves' disease, after previous thyroid surgery. Little is known about the outcome of this treatment compared to patients with no previous surgery. A total of 20 patients who had received surgical treatment for Graves' hyperthyroidism 1-46 years previously and with relapse of the hyperthyroidism, and 25 patients with hyperthyroidism due to Graves' disease and no previous thyroid surgery were treated with radioiodine, following the same protocol. Early after treatment the previously operated patients showed a higher sensitivity to radioiodine, with more cases of early hypothyroidism, than non-operated patients. However, after 50 months of follow-up the outcome was identical. The results indicate that frequent assessment is necessary after radioiodine treatment of previously operated patients, since some patients develop early hypothyroidism.

Adult↗
PubMed1992

Sensitive enzyme-linked immunosorbent assay for measurement of autoantibodies to human thyroid peroxidase.

The development of a sensitive assay for detection of autoantibodies against one of the major thyroid antigens, thyroid peroxidase (TPO), is described. TPO was purified from human thyroid tissue by: (1) isolation of thyroid microsomes using homogenization and differential centrifugation, (2) solubilization of membrane proteins by Zwittergent 3-14, and (3) anion exchange liquid chromatography on a FPLC Mono Q column. Autoantibodies against TPO (TPO-Ab) were measured using an enzyme-linked immunosorbent assay (ELISA) with serum samples diluted 1:100. Standards containing 70, 7, 0.7, 0.02 and 0 U ml-1 TPO-Ab were employed (reference standard code 66/387 NIBSC, London, UK). The detection limit was 0.02 U ml-1 corresponding to 2 U ml-1 in undiluted serum. The inter- and intra-assay coefficients of variation were 8.6% and 5.3%. In 109 healthy control subjects TPO-Ab was found in 9 (8.3%), while 43 (97.7%) out of 44 patients with newly diagnosed untreated Graves' disease had detectable TPO-Ab in serum. All of 16 patients with newly diagnosed spontaneously developing primary hypothyroidism had circulating TPO-Ab (range 16-7000 U ml-1). The new assay is a valuable tool for evaluation of thyroid autoimmunity in individual patients and for studying the epidemiology of thyroid autoimmunity.

Adolescent↗
PubMed1991

High incidence of multinodular toxic goitre in the elderly population in a low iodine intake area vs. high incidence of Graves' disease in the young in a high iodine intake area: comparative surveys of thyrotoxicosis epidemiology in East-Jutland Denmark and Iceland.

Little is known about the optimum level of iodine intake for iodine supplementation programmes, or about the effects of the high levels of iodine intake that are found in some countries. We compared the incidence of different types of hyperthyroidism in East-Jutland Denmark with a low average iodine intake but no endemic goitre, and the incidence in Iceland with a relatively high iodine intake. Hyperthyroidism was more common in East-Jutland than in Iceland, due to a much higher incidence of multinodular toxic goitre and also of single toxic adenoma. Most of the patients with these diseases were over 50 years of age. By contrast, the incidence of Graves' disease was significantly higher in Iceland than in East-Jutland. This difference was most marked in the younger age groups, in which hyperthyroidism was more than twice as common in Iceland as in East-Jutland. These results demonstrate that even mild iodine deficiency has a significant effect on population health, since it leads to a high incidence of autonomous thyroid nodules with hyperthyroidism in the elderly population. However, population iodine intake probably should not exceed a level much higher than that necessary to avoid iodine deficiency, otherwise Graves' disease may be induced in the young population.

Adolescent↗
PubMed1991

Relations between diurnal variations in serum osteocalcin, cortisol, parathyroid hormone, and ionized calcium in normal individuals.

Serum osteocalcin varies in a diurnal rhythm, with peak values during the night and minimum levels before noon, but the factors controlling this rhythm are unknown. In this study, we evaluated the temporal relations between the osteocalcin rhythm and variations in serum concentrations of cortisol, intact parathyroid hormone (PTH(1-84)), and ionized calcium (Ca2+) in 15 normal volunteers, aged 22-46 years. Serum cortisol varied in a typical way preceding inverse changes in serum osteocalcin by about 4 h (r = 0.78, p less than 0.0001). Changes in serum osteocalcin following the early morning increase in serum cortisol were statistically indistinguishable from the changes seen after oral administration of 2.5 or 10 mg of prednisone. Serum PTH (1-84) showed a diurnal rhythm (p less than 0.01) with peak values (4.06 +/- 0.42 pmol/l) at 20.30 h and nadir (2.81 +/- 0.10 pmol/l) around 10.30 h, preceding changes in serum osteocalcin in the same direction by 5 h (r = 0.55, p less than 0.02). Prednisone at a dose of 10 mg did not change the time course significantly. Serum Ca2+ varied in an almost bi-phasic pattern (p less than 0.01) with maximal mean levels around 16.30 and 09.30 h and minimal levels around 05.30 and 14.30 h. Serum Ca2+ correlated inversely with PTH (1-84) (r = 0.53, p less than 0.01), and serum osteocalcin was inversely related to Ca2+ at concurrent time points (r = 0.59, p less than 0.005). Prednisone caused a 2-3 h lasting increase in serum Ca2+ 3-5 h after ingestion (p less than 0.001). In conclusion, our results suggest that cortisol is strongly associated to the diurnal rhythm in serum osteocalcin. The biological relevance of the reported relation between serum osteocalcin and PTH (1-84) and serum Ca2+ is uncertain.

Administration, Oral↗
PubMed1991

Hyperfunctioning thyroid nodules.

The authors describe the principal clinical and pathological aspects of the solitary hyperfunctioning adenoma or the multifocal hyperfunction of a multinodular goitre. Successively they report the incidence of these conditions in countries with different iodine intake as well as the age distribution of the examined patients. In the area with low iodine intake the incidence of hyperthyroidism caused by multinodular goitre is 10 times higher than in the high iodine intake area. Finally, the role of the laboratory in the diagnosis of hyperthyroidism and in identifying the type of hyperthyroidism is discussed; an up-todate flow-sheme is also reported.

Adenoma↗
PubMed1990

Turnover of thyrotropin-releasing hormone in patients with chronic renal failure and chronic alcoholic liver disease.

Homogenates of liver and kidney tissues are efficient in degrading TRH, but the liver contains only membrane-bound pyroglutamyl aminopeptidase, active in degrading TRH at the extracellular side of cell membranes. In the present study the effect of liver and kidney failure on the degradation of infused TRH was investigated in man. In 7 uremic patients (group I) and 7 patients with chronic alcoholic liver disease (group II) plasma clearance rate, half-time of disappearance (t1/2) and half time of disappearance of TRH in serum in vitro (t1/2p) was determined. The plasma clearance rate, t1/2 and t1/2p were, respectively, 19.8 +/- 6.2 ml.kg-1.min-1, 6.6 +/- 1.5 min and 16.4 +/- 6.2 min in group I versus 28.2 +/- 4.8 ml.kg-1.min-1, 9.3 +/- 2.6 min and 25.3 +/- 15 min (mean +/- SD) in group II. The volume of distribution of TRH was 19.3% of the body weight in group I and 36.5% in group II. The calculated half-time in the extravascular tissue compartment (t1/2) was 5.4 +/- 1.4 min in group I and 9.2 +/- 2.7 min in group II patients (mean +/- SD). TRH metabolism in the uremic patients was almost identical to that previously reported in normal subjects. In the patients with chronic liver disease plasma clearance rate was significantly greater than in normal subjects, indicating an increased TRH-degrading enzyme activity in the tissue compartment. However, owing to the very large expansion of this compartment, the t1/2 and t1/2t were significantly prolonged. Hence, half-time determination of TRH is no reliable indicator of overall TRH degradation in patients with liver disease.

Adult↗
PubMed1989

Paradoxically subnormal serum T4 and T3 in dogs after prolonged excessive TSH stimulation of the thyroid caused by post-cAMP refractoriness of thyroid hormone secretion.

Several studies have demonstrated that excessive TSH stimulation of the thyroid for hours to days makes the thyroid gland less responsive to TSH. In this study we extended the period of excessive TSH stimulation of dog thyroids in vivo to 28 days. Serum T4 and T3 were considerably elevated initially but then gradually declined and became paradoxically subnormal after 3 weeks. This was not caused by production of TSH antibodies. At day 28 the thyroid lobes were perfused for measurements of T4 and T3 secretion. Both the basal secretion rate and the response to TSH were considerably lower after TSH pretreatment than in control dogs. This was not due to reduction of TSH receptors because the response to forskolin was similarly reduced. The cAMP response to TSH and forskolin was not blunted by TSH pretreatment. The total amount of thyroglobulin in the thyroid was not significantly altered by TSH pretreatment, but the T4, T3, and iodine content of thyroglobulin was reduced to 50% to 70% of control levels. Such a moderate reduction in hormone content could not explain the development of subnormal serum T4 and T3 during intensive TSH stimulation. Apparently one or more processes involved in thyroid hormone secretion after cAMP generation were made so refractory to TSH by the prolonged excessive stimulation, that a state of biochemical hypothyroidism developed.

Animals↗
PubMed1989

Rat heart thyroxine 5'-deiodinase is sensitively depressed by amiodarone.

Thyroxine 5'-deiodinase activity (5'-D) is depressed in rat liver by amiodarone. To investigate the possible tardive effect of amiodarone on 5'-D in different tissues, rats were fed amiodarone according to a short-term (group A, 50 mg amiodarone/kg/day for 10 days, total dose 150 mg, n = 16) and long-term regimen (group B, 25 mg amiodarone/kg/day for 20 days, n = 16) (control group, n = 12). Serum, heart, and other tissues were collected for 10 days after drug cessation. Thyroxine (T4), triiodothyronine (T3), amiodarone, and its active metabolite desethylamiodarone (DEA) were determined in serum, and 5'-D was determined in tissues. In group A, amiodarone concentrations in the heart at the time of drug cessation were two times higher than in group B. Higher amiodarone concentrations were also found in other tissues, and DEA was immeasurable in nearly all tissues at all times. In all tissues the amiodarone content declined rapidly. 5'-D was depressed to about 50% of controls (p less than 0.05) in heart throughout the 10-day observation period, despite unmeasureable drug levels (less than 0.03 microgram/g tissue). In contrast, liver and kidney 5'-D normalized after the first day in both treated groups, while muscle 5'-D did not differ from controls at any time. In conclusion, heart 5'-D seems to be more sensitively depressed by amiodarone than other tissues. Inhibition of thyroid hormone effect in the heart may contribute to the antiarrhythmic properties of amiodarone; however, it cannot be concluded that amiodarone is responsible for the tardive drug effect.

Amiodarone↗
PubMed1989

Calcium stimulates the release of calcitonin gene-related peptide from the canine thyroid.

The calcitonin gene in the thyroid parafollicular cells generates two different mRNAs, which encode for the precursors of calcitonin and calcitonin gene-related peptide (CGRP). In this study, we investigated whether these two peptides are released simultaneously in the perfused dog thyroid. The isolated dog thyroid (n = 10) was once-through perfused with a Krebs-Ringer bicarbonate buffer. After elevation of the buffer Ca2+ concentration from 1.5 to 2.5 mM, a rapid, marked, and parallel secretion of both calcitonin and CGRP occurred (P less than 0.001). By stepwise increase of the buffer Ca2+ concentration, it was found that, although an elevation from 1.5 to 1.65 mM had no influence on the thyroid output of calcitonin or CGRP, elevations to 1.75, 2.0, and 2.5 mM of Ca2+ induced dose-dependent parallel increases in the thyroid output of calcitonin and CGRP. Furthermore, the stimulation with pentagastrin (100 pM) increased the thyroid output of both calcitonin and CGRP in parallel. It is concluded that the normal dog thyroid releases calcitonin and CGRP in parallel on stimulation with Ca2+ and pentagastrin.

Animals↗
PubMed1989

Thyroid hormone antibodies and Hashimoto's thyroiditis in mongrel dogs.

Abnormally elevated serum T3 concentrations measured by RIA were observed in 19 clinically euthyroid or hypothyroid mongrel dogs. The serum T4 concentrations in these sera were low, normal, or high. Measurement of the intensity of thyroid hormone binding to serum proteins was determined by equilibrium dialysis. A marked decrease in the percent free T3 was observed in these abnormal sera. Polyacrylamide gel electrophoresis, pH 7.4, of normal dog serum enriched with tracer 125I-labeled thyroid hormones demonstrated binding of [125I]T4 to transthyretin, thyroid hormone-binding globulin, and albumin and of [125I]T3 primarily to thyroid hormone-binding globulin. In all abnormal sera, polyacrylamide gel electrophoresis demonstrated strikingly higher binding of T3 to immunoglobulin (Ig). Eleven of 16 abnormal sera had minimal to moderate binding of T4 to Ig. The percent free T4 was lower only in dogs whose sera demonstrated markedly increased binding of T4 to Ig. All abnormal sera tested had positive antithyroglobulin antibodies, consistent with the diagnosis of autoimmune lymphocytic thyroiditis. As in humans, antibodies to thyroid hormones in dogs are more common in the presence of Hashimoto's thyroiditis and should be considered when elevated serum thyroid hormone concentrations are observed in the absence of clinical thyrotoxicosis. When an antibody to only one thyroid hormone is present, a marked discrepancy in the serum concentrations of T3 and T4 will be observed.

Animals↗
PubMed1989

Effects of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism.

Administration of human GH to GH-deficient patients has yielded conflicting results concerning its impact on thyroid function, ranging from increased resting metabolic rate to induction of hypothyroidism. However, most studies have been casuistic or uncontrolled and have used pituitary-derived GH of varying purity, often contaminated with TSH. Therefore, we conducted a double blind, placebo-controlled cross-over study of the effect of 4 months of biosynthetic human GH therapy (Norditropin; 2 IU/m2.day) on thyroid function in GH-deficient adults (8 females and 14 males; mean +/- SE age, 23.8 +/- 1.2 yr). One group (I) was euthyroid without T4 substitution (n = 13), whereas the other (group II) received T4 (n = 9). Serum T4 (nanomoles per L) decreased in both groups after GH treatment [group I, 100 +/- 8 (mean +/- SE) vs. 89 +/- 8 (P less than 0.01); group II, 145 +/- 18 vs. 115 +/- 10 (P less than 0.05)]. Conversely, GH treatment caused an increase in serum T3 (nanomoles per L) in both groups [group I, 1.9 +/- 0.1 vs. 2.0 +/- 0.1 (P less than 0.1); group II, 1.7 +/- 0.1 vs. 1.9 +/- 0.1 (P less than 0.05)]. Similar changes were seen in serum free T4 and T3. The serum T3 level during the placebo period of group I was significantly lower than that in an age-matched reference group (P less than 0.02). Serum rT3 (nanomoles per L) was low in group I and decreased significantly, as in group II, after GH treatment [group I, 0.26 +/- 0.02 (placebo) vs. 0.20 +/- 0.02 (GH; P less than 0.01); group II, 0.38 +/- 0.05 (placebo) vs. 0.29 +/- 0.02 (GH; P less than 0.01)]. Serum TSH decreased in both groups during GH therapy, though not significantly. Serum thyroglobulin was unaltered and did not differ from that in the reference group. In conclusion, our data are consistent with a GH-induced enhancement of peripheral deiodination of T4 to T3. GH thus seems to play an important role, either directly or indirectly, in the regulation of peripheral T4 metabolism.

Adult↗
PubMed1988

The adenylate cyclase system and calcitonin secretion from perfused dog thyroid lobes.

The aim of the study was to assess the involvement of the adenylate cyclase system in calcitonin (CT) secretion from thyroidal C-cells. The cAMP analogues Br-cAMP (10(-6) and 10(-4) mol/l) and DB-cAMP (10(-4) mol/l) and the activators of adenylate cyclase cholera toxin (0.1 microgram/ml and 5 micrograms/ml) and forskolin (10(-7) mol/l and 10(-5) mol/l) were infused for 6 min periods in perfused dog thyroid lobes. CT was measured in thyroid effluent by radioimmunoassay. Br-cAMP and cholera toxin did not alter basal CT secretion. DB-cAMP had a minimal stimulatory effect and forskolin 10(-5) mol/l a moderate stimulatory effect. This was much less than the effect of increasing perfusate Ca++ from 1.5 to 2.0 mmol/l. 10(-4) mol/l Br-cAMP increased the response to Ca++ with approximately 50 per cent. These results suggest that the activity of the adenylate cyclase system of the C-cells by itself is of little importance for CT secretion, but that it may have a role as modulator of the response to Ca++.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1988

Solid-phase iodothyronine-5'-deiodinase (5'-D) assays applied in production of monoclonal antibodies against 5'-D.

Characterization of iodothyronine-deiodinating enzymes has been difficult due to loss of enzyme activity during purification. To obtain a new tool for studying these enzymes we investigated the possibility of developing monoclonal antibodies (MAbs) against iodothyronine-5'-deiodinase (5'-D). Two specific and sensitive solid-phase microassays were developed for screening hybridoma supernatants for the presence of antibodies inhibiting rat kidney 5'-D and antibodies binding to but not inhibiting the enzyme. BALB/c mice were immunized with a 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate (CHAPS)-solubilized 5'-D-rich membrane preparation from rat kidney cortical tissue. Spleen cells were fused with NSI-Ag 4/l mouse myeloma cells by means of polyethylene glycol. Two hybridoma cell lines (AF5 and BE8) secreting MAbs specifically binding to without inhibiting 5'-D were produced. The AF5 antibody was of the IgG2a subclass and the BE8 antibody of the IgG2b subclass. Binding of one of the antibodies to the enzyme inhibited binding of the other in both an enzyme-linked immunosorbent assay (ELISA) and a specific enzyme-binding assay. CHAPS-solubilized kidney microsomal fraction was chromatographed on a Sepharose 6B column. Elution profiles of 5'-D activity and MAb-binding antigens, as measured by ELISA with both AF5 and BE8, were identical. Monoclonal antibodies should be valuable probes in the further elucidation of the nature of the iodothyronine-deiodinating activity in various tissues.

Animals↗
PubMed1988

Amiodarone inhibits T4 and T3 secretion but does not affect T4 deiodination to T3 in perfused dog thyroid lobes.

Amiodarone interferes with thyroid hormone homeostasis in several ways. In the present study we assessed if amiodarone has direct effects on thyroid secretion of T4 and T3 and on intrathyroid T4 deiodination to T3 as studied in perfused dog thyroid lobes. 10(-4) mol/l amiodarone inhibited the TSH stimulated T4 secretion to 73.0 +/- 8.3 per cent of control (mean +/- SE, n = 4, p less than 0.05) and T3 secretion to 68.3 +/- 6.2 per cent of control (p less than 0.05). Amiodarone did not alter intrathyroidal T4 deiodination to T3 since the T4/T3 ratio in thyroid effluent was not affected. The mechanism behind the amiodarone effect on the thyroid is unknown but probably different from that responsible for the effect of certain other iodine containing aromatic compounds (e.g. ipodate).

Amiodarone↗
PubMed1987

Axonal transport of slow component a in sciatic nerves of hypo- and hyperthyroid rats.

Axonal transport of slow component a was studied in dorsal root afferents of the sciatic nerves of hypo- and hyperthyroid rats. Three experimental groups of rats were made hypothyroid at the age of 12 weeks by the administration of 131I. From the age of 22 weeks to the end of the study, the groups were treated with daily subcutaneous injections of thyroxine in various doses to make them hypo-(0 microgram/100 g), normo- (1 microgram/100 g), and hyperthyroid (6 micrograms/100 g), respectively. The hypothyroid group had a moderate thyroid hormone deficiency (a serum triiodothyronine level of 0.19 +/- 0.10 nmol/L and a heart/body weight ratio of 1.87 +/- 0.09 g/kg at time of killing compared with 0.60 +/- 0.09 nmol/L and 2.18 +/- 0.06 g/kg, respectively, for the control group). The hyperthyroid group was severely deranged, with serum triiodothyronine being 3.30 +/- 0.37 nmol/L and a heart/body weight ratio of 3.11 +/- 0.16 g/kg. The hypothyroid rats showed a reduction in mean velocity for the transport of slow component a (0.80 +/- 0.07 mm/day compared with 0.91 +/- 0.05 mm/day in the controls). The width of the wave of activity was smaller for the hyperthyroid group than for the control group (6.6 +/- 0.7 mm compared with 8.1 +/- 1.2 mm), suggesting an increased clearance of the axonally transported activity in the proximal axon. A decrease in transport of slow component a in hypothyroidism may be the explanation of peripheral neuropathy with axonal degeneration occasionally seen in patients with severe myxoedema.

Animals↗