Simple goiter and its variants: euthyroid and hyperthyroid multinodular goiters.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Studer
Publications and source records attributed to H Studer.
The pathogenesis of "hot" and "cold" follicles in multinodular goiters.
The prominent characteristics of euthyroid and hyperthyroid human nodular goiters are the regional variability of iodine metabolism and the appearance of "hot" autonomous follicles. No explanation for the pathogenesis of the interfollicular heterogeneity of iodine turnover has yet been offered. We have investigated whether the recently demonstrated polyclonality of normal follicular epithelia could possibly be related to goiter heterogeneity. The present work demonstrates, by means of autoradiographic and histological techniques, that single cells or tiny cell families with widely differing metabolic properties are normally present within single mouse, rat, and human thyroid follicles. In animals, intercellular heterogeneity is demonstrated in respect to 1) iodinating capacity, 2) peroxidase content, 3) endocytotic response to TSH, and 4) proneness to replicate. Moreover, [3H] thymidine labeling of stimulated mice thyroids reveals that mitotic cells are not randomly distributed; some follicles contain large colonies of rapidly replicating cells, and these clonogenic cells give rise to new follicles. Since simple goiter formation invariably implies replication of normal thyroid follicles, we conclude that the large differences in iodine turnover among the follicles of simple goiters are a consequence of the generation of new, metabolically heterogeneous follicles from genetically distinct cell clusters existing with the epithelia of all normal mother follicles.
Animals↗
Experimental conditions leading to a low degree of thyroglobulin iodination without loss in coupling efficiency.
The hormone content of in vitro iodinated thyroglobulin is a constant fraction of the iodine content of the protein under most, but not all, experimental conditions. In contrast, in vivo iodinated human thyroglobulin may contain as little as 10% or as much as 50% of its total iodine in the T4 molecules. Surprisingly, in some poorly iodinated thyroglobulins up to 30% of the iodine may be found in T4. The mechanism of the apparent dissociation between iodination and coupling efficiency (i.e. percentage of total iodine present as iodothyronines) may be dilution of pre-existing high iodinated thyroglobulin stores by non-iodinated prethyroglobulin. This hypothesis was tested by feeding rate PTU and KClo4 for 9 days and injecting T4 during the last 2 days. Thyroglobulin iodination dropped from 0.9 ot 0.13% but the coupling efficiency remained unchanged at 25.7 and 23.9%. The exchange of highly iodinated thyroglobulin molecules for non-iodinated ones is one of the two in vivo mechanisms suggested so far which can lead to an apparent dissociation of thyroglobulin iodination and coupling efficiency.
Animals↗
Thyroxine-rich iodopeptides as fragment of reduced guinea pig thyroglobulin.
Full reduction of guinea pig thyroglobulin with mercaptoethanol followed by polyacrylamide gel electrophoresis reveals the presence besides the well known three polypeptide chains, of small amounts of iodopeptides with a molecular weight of 3 000 to 46 000 daltons. One of these peptides with a molecular weight of roughly 10 000 daltons has a much higher efficiency to couple iodotyrosines into thyroxine than any other fragment of thyroglobulin. Despite its small quantity this peptide contributes more than one third to the total thyroxine synthesis from a given iodide shot at any time up to five days after its injection. Iodopeptides akin to that found in guinea pigs were recently described by several authors in different species. They probably represent the preferential domains for hormone synthesis within the intact thyroglobulin molecule.
Animals↗
Pathogenesis of thyroid nodules in multinodular goiter.
Pathogenesis of nodule formation was studied in over 100 nodular goiters from a subendemic area. 60 surgical specimens were autoradiographed. Only one classical, well-encapsulated adenoma was detected. All other nodules were incompletely encapsulated and consisted of follicles that were morphologically and functionally identical to those of nonnodular parenchyma. Most characteristic was the tremendous interfollicular heterogeneity appearing on autoradiographs. Nodular goiters contain multiple foci and strands of fibrous tissue, which result from scarring of multiple hemorrhagic necroses occurring during goiter growth. Therefore, the slowly growing number of newly formed follicles has to squeeze into the meshes of an inelastic network of connective tissue. Nodular growth pattern is the inevitable consequence. Some particular nodules expand because of excessive accumulation of colloid. We conclude that most thyroid nodules in long-standing goiters consist of ordinary, polyclonal goiter follicles which expand in nodular fashion because they replicate within a mold made out of a poorly extensible network of connective tissue.
Autoradiography↗
[Which thyroid diseases should be surgically treated?].
Explore the source record for details and available documents.
Adolescent↗
[Amiodarone and the thyroid gland].
In an estimated 5% of patients, antiarrhythmic therapy with amiodarone (Cordarone) may have side effects involving thyroid function. These unwanted effects on the thyroid gland can be classified into three entirely different categories. In addition, amiodarone invariably interferes in a characteristic way with the peripheral metabolism of thyroid hormones at the cellular level. These effects are reviewed. 1. Amiodarone contains 39% of iodine. Since its metabolism involves deiodination to inorganic iodide, classical iodine-induced thyrotoxicosis may occur in patients with nodular goiters containing autonomous follicles. 2. An entirely different form of thyrotoxicosis, resembling Graves' disease, may be induced by amiodarone in individuals with previously normal thyroid. The pathogenesis of this phenomenon is unknown. 3. In rare patients of the thyroid gland is unable to cope with pharmacological quantities of iodide, possibly due to genetic anomaly of thyroid metabolism. In these individuals amiodarone may induce hypothyroidism. 4. In contrast to the possible side effects of amiodarone involving the thyroid gland, the drug has an obligate impact on the metabolism of thyroid hormones at the level of the peripheral cells. It inhibits the peripheral conversion of thyroxin to triiodothyronine (T3) and favours the generation of reverse T3, which has no T3 activity. This and other arguments favour the assumption that the effects on the heart observed after prolonged amiodarone treatment are in fact due to selective local hypothyroidism.
Adult↗
[Steroid withdrawal syndrome. A current problem of outpatient medicine].
In contrast to a widespread belief, the authors consider a single measurement of serum cortisol concentration in the early morning to be a reliable and simple outpatient screening method for detecting spontaneous or iatrogenic adrenal insufficiency. In patients on steroids the method allows detection of iatrogenic damage to the adrenals while steroid therapy is still continuing. Important guidelines for the conduct of a planned attempt to withdraw steroids can thus be obtained. Routine use of early morning cortisol measurements has greatly improved clinical knowledge about the multifaceted steroid-withdrawal syndromes (SWS). The symptoms of classical adrenal insufficiency in the form of SWS are described, as are the often atypical signs and symptoms occurring when the disease initially calling for steroid treatment is still active during attempts to lower the therapeutic dose. In addition, attention is drawn to SWS due to psychological causes.
Addison Disease↗
[Antinatriuretic effect of sulfinpyrazone].
Clinical observations suggest that sulfinpyrazone (Anturan) may lead to edema formation in borderline compensated cardiac insufficiency. Since the drug is increasingly used in secondary prophylaxis of sudden death after myocardial infarction, a trial was designed to confirm or to refute the suspicion that sulfinpyrazone may interfere with natriuresis. In two experimental series, 18 volunteers were given a sodium load of 5 g or 6 g and natriuresis was first measured at hourly intervals for 4 hours and thereafter for an additional 4-hour period. The experiment was repeated with a single dose of 400 mg sulfinpyrazone given with the sodium load. In the first, non-randomized trial (n = 8) 71.2 +/- 20.7 (SD) mval Na was excreted within 8 hours without, and 41.2 +/- 20.6 mval with sulfinpyrazone (p less than 0.05). In the second, randomized trial (n = 10), sodium excretion fell from 74.2 +/- 38.0 mval/8 h in the control experiment to 43.5 +/- 20.6 mval/8 h after sulfinpyrazone (-42%; p less than 0.05). Excretion of potassium and creatinine remained unchanged. It is concluded that sulfinpyrazone does indeed interfere with normal renal sodium excretion and that the phenomenon may be relevant in patients with borderline compensated myocardial insufficiency. The design of the trial provides a relatively easy way to obtain valuable information on the clinically relevant antinatriuretic side effects of many drugs, particularly that of non-steroidal antiinflammatory agents.
Adult↗
[The treatment of arrhythmias with amiodarone].
The efficacy of amiodarone in the treatment of cardiac arrhythmias is discussed in the light of published results and our own experience. Oral and intravenous administration are compared with respect to electrophysiologic changes in the heart. The possibility that these changes are mediated by amiodarone-induced inhibition of metabolic pathways in cardiac tissue which depends on thyroid hormone is discussed. Among the undesirable effects, chief consideration is given to thyroid function disturbances.
Administration, Oral↗
Prevalence of various degrees of hypothyroidism among patients of a general medical department.
We have measured basal thyrotropin (TSH) in 945 consecutive patients of a general medical department. Additional thyroid tests were carried out in patients with elevated TSH. Thirty patients (3.1%) had subclinical hypothyroidism, i.e. an elevated TSH with no clinical signs and with a normal free thyroxine index. A cause was found in only fifteen of these thirty patients. Thirteen additional patients (1.37%) had mild or overt primary hypothyroidism, three of which were already diagnosed. This prevalence is three times higher than that found in a retrospective survey at the same hospital. Of the ten newly-detected cases five were discharged on thyroid hormone replacement. In two patients the antithyroid drugs which were the cause of hypothyroidism were discontinued. The remaining three patients had severe non-thyroidal illnesses and thyroid hormone was not prescribed. A cause for the hypothyroidism (autoimmune thyroid disease, post-radioiodine, post-thyroidectomy or antithyroid drugs) was established in all but two cases. The data suggest that thyroid function tests (preferably a TSH) should be performed on any patient with prior treatment to the thyroid and, in addition with very broad indications, perhaps even routinely, in all women over 50 years of age.
Adult↗
The effect of antipyrine, phenobarbitol and rifampicin on thyroid hormone metabolism in man.
The effect of three different live microsomal enzyme inducing drugs on thyroid hormone metabolism was investigated. Seven volunteers were randomly allocated in a crossover design to either antipyrine (1200 mg), phenobarbital (100 mg) or rifampicin (1200 mg) daily for 14 days. Before and after each treatment the following parameters of enzyme induction were measured: antipyrine clearance, gamma-glutamyltranspeptidase, d-glucaric acid and 6-beta-hydroxycortisol urinary excretion. In addition, thyroxine-binding globulin (TBG), T3-resin uptake (RT3U), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3), reverse T3 (rT3), and thyroid stimulating hormone were estimated. Following antipyrine and phenobarbital antipyrine clearance increased by about 45%, while with rifampicin an increase of 125% was observed. The indices of thyroid function did not change following phenobarbital and antipyrine, but after rifampicin T4, FT4 and rT3 decreased by about 14%, and T3 increased by 25%. In addition, the impact of rifampicin on the clearance of injected 125I-T4 was investigated in six additional volunteers by blocking thyroid iodine uptake. The 125I-T4 halflife decreased from 155 to 106 h and its clearance increased from 25 to 50 ml/h, while a fall in T4, FT4 and rT3 by about 40% and no rise but a decrease in T3 by 25% occurred. Therefore an increased clearance of T4 and rT3 but not of T3 seems likely following rifampicin, which might be due to enhanced hepatic metabolism and biliary excretion.
Adult↗
Borderline low thyroid function and thyroid autoimmunity. Risk factors for coronary heart disease?
Assessments were made of 945 consecutive hospital patients with regard to a relation between borderline low thyroid function (recognised by a slightly raised thyroid stimulating hormone), thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid autoimmunity, serum cholesterol, and coronary heart disease. Men and women with a thyroid stimulating hormone of 4.0 mU/l or over had a higher prevalence of coronary heart disease than did age-matched controls, and this difference was significant in women. The excess of coronary heart disease was not explained by an excess of other risk factors such as a high cholesterol, hypertension, smoking, and diabetes. Women with thyroid antibodies had a slightly higher prevalence of coronary heart disease despite the unexpected finding of a lower serum cholesterol. The data point to an association between borderline thyroid function and autoimmunity and coronary heart disease which is not mediated through a raised serum cholesterol.
Adult↗
Reaccumulation of thyroglobulin and colloid in rat and mouse thyroid follicles during intense thyrotropin stimulation. A clue to the pathogenesis of colloid goiters.
Since Marine's observations some 50 years ago, it has been generally accepted that colloid goiters invariably result from colloid repletion of originally hyperplastic goiters after cessation of the goitrogenic stimulus. However, clinical observations suggest that many goiters never go through a stage of hyperplasia, but are colloid-rich from the beginning. We have injected rats and mice with thyrotropin (TSH), three times a day for 4 d, while the animals were kept on an iodine-rich diet (HID). Additional groups of animals were fed an iodine-poor diet (LID) or a diet containing 0.15% propylthiouracil (PTU) or 1% sodium perchlorate (ClO4). At intervals, thyroid weight, DNA, iodine and thyroglobulin content, thyroglobulin iodination, and intracellular droplet formation were measured. Histologic sections were also prepared and stained with periodic acid Schiff. Furthermore, thyroxine concentration was measured in the serum. Thyroglobulin content dropped by approximately 30% in HID animals but by 60% in all other groups 1 d after starting TSH. Thereafter, thyroglobulin reaccumulation occurred and droplet formation correspondingly decreased despite continuous heavy TSH stimulation. The largest amount of thyroglobulin was reaccumulated in HID animals followed by the PTU/LID groups, whereas no reaccumulation was observed in the ClO4 group. Reaccumulation of thyroglobulin only occurred if there was concomitant organification of at least some iodine. The subsequent phases of depletion and reaccumulation of thyroglobulin were mirrored by the morphology of the follicular lumina, the staining properties of the colloid and the serum T4 concentration. These observations suggest that endocytosis gradually becomes refractory to continuous TSH stimulation if a certain minimal amount of iodine is available for organic binding. Thus, primarily colloid-rich goiters may form in the presence of continuously higher than normal thyrotropin levels without a previous stage of follicular hyperplasia. The view should be revised that accumulation of colloid and intense thyrotropin stimulation are mutually exclusive events.
Animals↗
Changes in the polypeptide assembly of guinea pig thyroglobulin induced by thyrotropin-regulated thyroid activity.
We have previously reported that the relative proportion of three polypeptide chains in guinea pig thyroglobulin is closely related to the iodine content of the protein. The present work demonstrates that it is not the iodine content per se but, rather, TSH-regulated thyroid activity which modulates the substructure of thyroglobulin. In a first set of experiments, the impact of TSH stimulation on sodium dodecyl sulfate (SDS)-induced dissociation of 19S thyroglobulin into 12S subunits was compared to that of iodination. While in control animals the ratio of 12S to 19S thyroglobulin was 48:52, it changed to 35:65 in glands strongly stimulated with TSH and blocked with MMI. This rise in the relative proportion of 19S thyroglobulin occurred despite a simultaneous drop of iodine content from 0.6% to 0.24%. It was only after TSH suppression that the well known inverse correlation between the level of iodination and dissociability reappeared. In a second set of experiments, SDS-treated thyroglobulin was fully reduced by splitting disulfide bonds with mercaptoethanol. In addition to the previously described three polypeptide chains, A, B, and C, a hitherto neglected nonreducible fraction comigrated with 19S thyroglobulin on polyacrylamide gels. Native thyroglobulin with widely varying iodine contents was obtained from unstimulated glands and from glands strongly stimulated with TSH. Drastic changes in the polypeptide chain assembly, depending on the degree of TSH stimulation but entirely independent of iodination, were observed. There was a strong negative correlation between the nonreducible 19S thyroglobulin fraction and both the B and C polypeptide chains with all experimental manipulations. We conclude that thyroglobulin substructure is highly dependent on the degree of TSH stimulation of the thyroid. TSH, through stimulation of unknown metabolic pathways, is a more important determinant of thyroglobulin substructure than the degree of iodination of the protein.
Animals↗
Topographical heterogeneity of basal and thyrotropin-stimulated adenosine 3'5'-monophosphate in human nodular goiter.
Explore the source record for details and available documents.
Animals↗
[Development of tolerance to the hemodynamic effects of nitroglycerin].
Explore the source record for details and available documents.
Adult↗
[Iodine deficiency is still endemic in Switzerland].
To obtain information on the present state of iodine supply in Switzerland random urine samples have been collected from 770 individuals for the purpose of measuring iodine and creatinine excretion. As a first step the widely used method of measuring iodine concentration per gram creatinine in casual urine samples was validated by quantitatively collecting urines for 6 consecutive 4 h periods in 11 healthy volunteers. True ioduria could thereby be compared with that calculated from random samples. 83% of all values were found to be within +/- 30% of the true mean value. The mean iodine content of all 770 samples collected in the field study was 93.3 microgram per gram creatinine (I/Cr). This mean value is slightly below the adequate iodine supply. Of even more concern is the fact that less than 60 microgram I/g Cr was found in 20% of all samples. Therefore, in the population sample as a whole the mean ioduria is still clearly below that indicating a sufficient iodine supply, and in one out of five individuals iodine excretion was typical of marked iodine deficiency. Low ioduria correlated significantly with low natriuria in both male and female subjects. This finding indicates that iodized table salt is an important though inadequate source of alimentary iodine. The increase in iodine admixture to table salt already agreed upon appears to be an appropriate means of improving nutritional iodine availability. Iodine deficiency may still be an important cofactor in the high prevalence of goiter in Switzerland. The long established goiter prophylaxis by iodine admixture to table salt may have lost part of its efficiency due to the sharp decrease in per capita consumption of salt.
Creatinine↗