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U Bürgi

Publications and source records attributed to U Bürgi.

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Can serum thyroglobulin predict the effect of thyroid hormone therapy on goitre growth?

Serum thyroglobulin and goitre size were followed in 22 patients with simple goitre or single thyroid nodules during 9 months of thyroxine therapy, to see whether alterations in serum thyroglobulin correlated with changes in goitre size. In the case of such a correlation serum thyroglobulin could be used to predict which goitres respond to thyroxine therapy and which require surgery. Pretreatment serum thyroglobulin was elevated in 11 patients. It normalized in one of 7 patients whose goitre did not shrink and in none of the 4 patients whose goitre shrank during thyroxine treatment. Thus no simple correlation exists between alterations in serum thyroglobulin and goitre size during short-term thyroxine therapy. Since other studies suggest that increased serum thyroglobulin indicates ongoing goitre growth, thyroxine treatment might have been unsuccessful in all patients with persistently elevated serum thyroglobulin with a longer follow-up. The presence of predominantly thyroxine responsive tissue together with some autonomously growing, thyroglobulin-releasing areas in the same goitre could explain the failure of serum thyroglobulin to normalize in patients whose goitre shrank during therapy. The study shows that after eradication of iodine deficiency, thyroxine treatment is rarely successful in the Swiss goitre population and that surgical treatment is usually required.

Adult↗

Irreversible inactivation of lactoperoxidase in the course of iodide oxidation.

In the course of lactoperoxidase-catalysed I- oxidation, which is a model for the initial step of thyroid hormone biosynthesis, irreversible enzyme inactivation can occur if free molecular iodine (I2) or other oxidized iodine species accumulate. Evidence is presented that the breakdown of the catalytic activity is the result of the iodination of the peroxidase-apoprotein. This kind of enzyme inactivation, which can be prevented by iodine acceptors' such as thyroglobulin or high concentrations of I-, may well play a role in the regulation of the synthesis of thyroid hormones in vivo.

Iodides↗

A disproportionate accumulation of fibrous tissue is not a causal factor in human goitre growth.

Histological preparations from human nodular goitres reveal the presence of variable and sometimes considerable amounts of acellular material separating the individual follicles. Part of this interstitial tissue consists histologically of fibrous strands. However, quantitative data on the fibrous tissue content of goitres are scarce. In the present study the proportion of fibrous tissue in normal human thyroids and human goitres was determined biochemically by measuring their content of collagen, the predominant component of fibrous tissue. Total collagen content increased in parallel to thyroid weight. The relative collagen content, however, decreased slightly but significantly with increasing thyroid weight. The collagen/DNA ratio (= fibrous tissue/cell number ratio) was not higher in goitres than in normal human thyroids. These results indicate that in goitre growth, there is no disproportionate accumulation of fibrous tissue accompanying the multiplication of thyroid follicular cells. They are in line with the earlier findings that despite histological heterogeneity, the main component of nodular goitres is newly generated follicles.

Age Factors↗

Evidence that the effect of triiodothyronine on epinephrine-stimulated lipolysis in white adipose tissue is mediated via nuclear receptors.

The decreased basal and catecholamine stimulated lipolysis in adipocytes from hypothyroid rats can be increased by thyroid hormone (TH) treatment. In the present study it was investigated whether this TH effect is mediated via nuclear receptors and synthesis of new proteins or via other mechanisms. Epinephrine stimulated lipolysis was measured in vitro in isolated white adipocytes. Decreased lipolysis in adipocytes from hypothyroid rats was increased to euthyroid levels when the animals received one dose of 15 micrograms triiodothyronine (T3)/100 g body weight (BW) iv 15 h before the adipocytes were prepared for the in vitro measurement of lipolysis. No effect of T3 on lipolysis could be seen when the T3 was given only 10 min. before obtaining adipose tissue for the in vitro measurements. The stimulation of lipolysis several hours after the administration of T3 could be abolished by the protein synthesis blocker cycloheximide. These data and our previous demonstration of nuclear T3 receptors in rat adipocytes are compatible with the assumption that the enhancement of lipolysis by TH is mediated via a mechanism involving nuclear TH receptors and synthesis of new proteins.

Adipose Tissue↗

[Goiter].

Studies in Switzerland (1979), in Austria (1982) and in Germany (1975) revealed that greater than 10% of the population has a goiter. Simple guidelines are offered to the practising physician for the work-up and therapy of this fairly common pathological condition. In the work-up one investigates firstly whether the goiter in question could be malignant, and, secondly, whether it could be due to thyroiditis. If this is not the case the goiter is probably benign (Graves' goiter or "simple" goiter). Malignant goiters are referred to the endocrinologist/surgeon for further work-up and therapy. Subacute thyroiditis is treated with salicylates or steroids. The hyperthyroid phase of thyroiditis is treated with beta-blockers and possibly steroids and the hypothyroid phase with thyroxine. The hypo- and euthyroid variants of "simple" goiter are treated with thyroxine. Goiters which grow during this therapy are removed surgically. The hyperthyroid variant of "simple" goiter should preferably be treated surgically.

Austria↗

Nuclear thyroid hormone receptors in cultured bone cells.

Thyroid hormones influence bone metabolism, but a direct interaction of triiodothyronine with nuclear T3 receptors in bone cells has not yet been reported. We investigated 125I-T3 binding to nuclei isolated from the cloned osteoblastlike rat osteosarcoma cells ROS 17/2.8. At 37 degrees C, saturable 125I-T3 binding to isolated nuclei reached equilibrium by 30 minutes and was completely displaced upon the addition of 500 nmol/L unlabeled T3. Nonsaturable binding represented about 0.5% of the radioactivity added (20% of the total binding). Thyroxine and 3,3',5'triiodothyronine competed with 125I-T3 with a 20-fold and 400-fold lower affinity than T3, respectively. Analysis of equilibrium competition experiments revealed the presence of a single class of homogeneous binding sites with an association constant of 5.0 +/- 0.3 X 10(9) mol/L-1 and a maximum nuclear binding capacity of 0.13 +/- 0.02 ng/mg DNA. A twofold increase of bone Gla protein (BGP) secretion was observed with T3 treatment suggesting that these T3 nuclear receptors are coupled with a biological response.

Animals↗

Brown fat nuclear triiodothyronine receptors in rats.

Brown adipose tissue (BAT) thermogenesis is important in the adaptation of body energy expenditure to cold exposure, fasting, and overfeeding and in the pathogenesis of obesity. Thyroid hormones are required for the normal functioning of BAT. The mechanism of their effect on BAT, however, has not yet been elucidated. Since most thyroid hormone effects are mediated via the binding of T3 to nuclear receptors (NT3R) the present studies were performed to investigate whether BAT contained NT3R and whether these NT3R were affected by cold exposure, fasting, overfeeding, or hypo- or hyperthyroidism. Rat BAT was found to contain NT3R with a maximum binding capacity (MBC) of 0.28 ng T3/mg DNA and a dissociation constant (Kd) of 3.2 X 10(-10) M. These parameters were unaffected by any of the experimental conditions studied. A major alteration of BAT NT3R MBC or Kd is thus not a causal factor in the changes in BAT thermogenesis induced by the above experimental conditions. In contrast, 3-wk overfeeding increased (+48%) and fasting decreased (-29%) the MBC of hepatic NT3R. Overfeeding increased serum T3 (+110%), while fasting decreased it (-37%).

Adipose Tissue, Brown↗

[Surgical treatment of hyperthyroid struma: surgery results, postoperative long-term course and study of a factor connected with recurrences].

None of the 335 patients thyroidectomized for hyperthyroidism in our department of surgery between 1972 and 1982 died as a consequence of the operation. Reassessment of 226 of these patients by questionnaire 68 +/- 25 (SD) months after thyroidectomy revealed the following complications: postoperative paresis of the recurrent nerve (9%), persistent change of voice (2%), and persistent hypoparathyroidism (3.5%). 91 patients underwent a follow-up investigation 74 +/- 33 months after thyroidectomy. Only one had recurrent hyperthyroidism but 6 had a recurrence of the goiter. Patients with recurrent goiters had a significantly higher frequency of increased serum thyroglobulin levels than patients without goiters. These results emphasize the effectiveness of surgical therapy in hyperthyroidism, and suggest that serum thyroglobulin might be a useful predictor for goiter recurrence.

Adult↗

Mechanism of enzymatic and non-enzymatic tyrosine iodination. Inhibition by excess hydrogen peroxide and/or iodide.

Non-enzymatic (I2-mediated) and lactoperoxidase-catalyzed iodination of tyrosine are inhibited by excess iodide (I-) and/or hydrogen peroxide (H2O2). This phenomenon is a consequence of the concentration-dependent dual role of I- and H2O2 in the iodinating system. I- and H2O2, in addition to their function as primary substrates of peroxidase, may act as alternative 'iodine acceptors' and therefore compete with tyrosine for the active iodinating agent, irrespective of whether this compound is an enzyme-associated iodinium cation (E X I delta +) or an equivalent oxidized iodine species (IOH, IC1, I2). The competitive reaction pathways resulting from excess I- and/or H2O2 in the iodination system are I2/I-3 generation and/or pseudo-catalatic degradation of H2O2, respectively. Our results also demonstrate that I2 (and alternative medium-dependent oxidized iodine species such as IOH and IC1) generated in the iodination system may play an important role as iodinating agent(s). They serve as a substitute for the enzyme-bound iodinium species (E X I delta +), if the prevailing I- concentration favours this pathway. The proposed mechanism of the various antagonistic and interactive reaction pathways is summarized in a scheme.

Binding, Competitive↗

[Diagnostic significance of blood thyroglobulin determination].

Thyroglobulin (Tg) is a protein which is synthesized in the thyroid. In healthy individuals only minute amounts of Tg can be found in the serum. In patients with thyroid disorders serum Tg levels are usually elevated, but the extent of this increase gives no indication of the nature of the underlying disease. Measurement of serum Tg is an established method in screening for thyroid disorders and in follow-up of patients with differentiated carcinomas of the thyroid. It seems likely that serum Tg determinations will also prove useful for other purposes (e.g. as an aid in deciding whether to treat a simple goiter by thyroid hormone administration or surgery).

Adult↗

The site of leakage of intrafollicular thyroglobulin into the blood stream in simple human goiter.

Serum thyroglobulin is increased in many thyroid diseases, including simple goiter. We followed thyroglobulin levels in 19 patients with diffuse and nodular euthyroid goiters by serial measurements of 80 samples over 2 yr. The large intraindividual variations suggested episodic release of thyroglobulin in this thyroid disease. To test the hypothesis that the phenomenon was due to sporadic release of colloid from diseased follicles, we studied 98 multinodular goiters by conventional histological techniques. Sixty-four surgical samples were auto-radiographed. Focal necrosis of single follicles as well as large necrotic areas, involving multiple follicles together with interstitial stroma, were found in 42% of the goiter specimens. The earliest stage of necrosis was focal death of epithelial cells, often followed by hemorrhages. Through the epithelial gaps, colloid leaked out into the interstitial space. In later stages, granulation tissue containing numerous macrophages invaded damaged follicles. Fibrous scars remained as ultimate witness of repair processes. In one chance observation, acute release of highly labeled thyroglobulin from follicular lumina into the interfollicular interstitium was autoradiographically documented. We conclude that the varying concentrations of thyroglobulin in serum of patients with simple goiter may result from episodic necrosis of follicles, permitting leakage of colloid into the interfollicular space.

Epithelium↗