Biomedical subjects

L Tegler

Publications and source records attributed to L Tegler.

At least 19 recordsLinked to original sources

PubMed1998

Is there a methimazole dose effect on remission rate in Graves' disease? Results from a long-term prospective study. The European Multicentre Trial Group of the Treatment of Hyperthyroidism with Antithyroid Drugs.

OBJECTIVE: The optimal antithyroid drug regimen for Graves' disease remains a matter of controversy. The European Multicentre Trial Group has investigated the effects of methimazole drug dose on the long-term outcome of Graves' disease. DESIGN: Extended follow-up of patients from a prospective multicentre trial, designed to study methimazole dose effects on the outcome of Graves' disease. We have reported previously that the relapse rates did not differ after a medication-free observation period of 12 months; the relapse rates were 37% and 38%, respectively. In this paper, we describe the outcome in these patients after a mean observation period of 4.3 +/- 1.3 years and have looked for potential predictors of this outcome. PATIENTS: Three hundred and thirteen patients with Graves' disease were randomized to treatment with a constant dose of 10 or 40 mg of methimazole for 1 year, with levothyroxine supplementation as required. MEASUREMENTS: At the time of inclusion into the trial: thyroid size, T4, T3, TSH-binding inhibiting immunoglobulins, urinary iodide excretion, thyroid uptake, Crook's therapeutic index of hyperthyroidism (a measure of clinical disease severity). At the time of follow-up examination: TSH, T4, T3, thyroid size, thyroid ultrasound, THS-binding inhibiting immunoglobulins. RESULTS: The overall relapse rate was 58%. There was no difference in relapse rates between patients treated with either 10 or 40 mg of methimazole (58.3 vs. 57.8%). Five patients had become spontaneously hypothyroid, without obvious relationship to antithyroid drug dose. Patients who relapsed and patients who remained in remission did not differ with respect to: age, goitre size, ophthalmopathy, median iodine excretion, serum T4 or serum T3, Crook's therapeutic index and thyroid uptake at the time of study entry. Thus, none of these variables was potentially suitable for predicting outcome. This finding was confirmed by Cox's proportional hazard regression. Thyroid volume, measured by ultrasound, did not differ between patients in remission and patients with relapse. There was no difference in the course of endocrine eye signs, in the requirement for steroid and radiotherapy for eye signs, or in thyroid echostructure between patients in the 10 and in the 40 mg group, nor was serum TSH different in patients who had remained in remission (0.8 +/- 0.6 mU/l in the 10 mg group, 1.0 +/- 0.8 mU/l in the 40 mg group). CONCLUSIONS: The dose of methimazole in Graves' disease therapy can safely be kept to the minimal required dose. This will provide the same chance of remission as higher doses, and provide the best balance of risk and benefit.

Adult↗

PubMed1995

Response to methimazole in Graves' disease. The European Multicenter Study Group.

OBJECTIVE: A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease. PATIENTS: Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months. MEASUREMENTS: Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase. RESULTS: Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size. CONCLUSION: Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.

Adult↗

PubMed1993

Basal and thyrotropin-stimulated secretion rates of thyroglobulin from the human thyroid gland during surgery.

The secretion rates of thyroglobulin were measured under basal conditions and after exogenous and endogenous thyrotropin stimulation in 23 patients during surgery. In 11 patients with normal thyroid glands the median secretion rate of thyroglobulin was 0.7 pmol/24 h. Higher secretion rates were observed in 8 patients with nontoxic nodular goiter (median 22 pmol/24 h; p < 0.001) and in 4 patients with thyroid malignancy (median 2.2 pmol/24h; p < 0.05). Within 10 min after administration of highly purified human thyrotropin into the thyroid artery an increase of the secretion rates was observed in the 9 patients studied with normal thyroid glands and 5 patients with nontoxic nodular goiter. TRH administration to 5 patients induced a slight but nonsignificant increase of the secretion rate of thyroglobulin after 20 min. These results show that thyroglobulin is secreted directly into the thyroid venous blood. They also confirm that thyrotropin is an important regulator of the thyroglobulin secretion.

Adult↗

PubMed1992

Hypoglycaemia and cardiac arrhythmias in patients with type 2 diabetes mellitus.

Improved blood glucose control by insulin treatment in patients with Type 2 (non-insulin dependent) diabetes mellitus increases the risk for hypoglycaemic episodes. Our objective was to investigate if hypoglycaemia causes electrocardiographic changes and cardiac arrhythmias in patients with Type 2 diabetes. Six insulin-treated patients with Type 2 diabetes and no known cardiac disease took part in the study. Hypoglycaemia was induced by insulin infusion aiming at a plasma glucose less than or equal to 2.0 mmol l-1 or hypoglycaemic symptoms. All patients experienced hypoglycaemic symptoms. The median lowest arterial plasma glucose was 2.0 mmol l-1. Arterial plasma adrenaline concentration increased from 0.4 +/- 0.1 (mean +/- SE) to 6.9 +/- 0.3 nmol l-1 (p less than 0.001) while serum potassium was lowered from 4.1 +/- 0.3 mmol l-1 to 3.5 +/- 0.2 mmol l-1 (p less than 0.001). The heart rate increased significantly during hypoglycaemia except in one patient who developed hypoglycaemic symptoms and a severe bradyarrhythmia at a plasma glucose of 4.4 mmol l-1. One patient developed frequent ventricular ectopic beats during hypoglycaemia while four patients showed no arrhythmia. ST-depression in ECG leads V2 and V6 was observed during hypoglycaemia in five patients (p less than 0.05) and four patients developed flattening of the T-wave. In conclusion, the study supports the hypothesis that hypoglycaemia in patients with Type 2 diabetes may be hazardous by causing cardiac arrhythmias.

Arrhythmias, Cardiac↗

PubMed1991

Thyroid epithelial cell proliferation in xenotransplanted human toxic nodular goitre is increased by Graves' IgG.

Human toxic nodular goitre tissue was xenotransplanted to athymic mice. Transplant function was analysed as 18-h thyroid transplant uptake of iodide-125 at day 21 and again at 10 weeks after transplantation. Graves' IgG or IgG from healthy donors was given intraperitoneally daily day 22-35. Epithelial cell proliferation in thyroid tissue transplants from human toxic nodular goitre and from normal thyroid glands was analysed by continuous [3H]thymidine administration for 4 days between day 21 and 24 and for 12 days between day 21 and 33 in separate series given daily injections of Graves' IgG or normal IgG during the same period. After administration of Graves' IgG, the 18-h iodide-125 uptake by the toxic nodular tissue transplants was 7 times higher at 10 weeks than at 3 weeks. Control IgG gave a corresponding 1.6-fold increase. The fraction of labelled cells after [3H]thymidine incorporation was 18 and 56% in toxic nodular goitre transplants and 4 and 48% in normal thyroid tissue transplants after daily Graves' IgG administration for 4 and 12 days, respectively, but only 1.3% in both types of tissue transplants after administration of normal IgG. Graves' IgG therefore seems to be able to stimulate cell proliferation in toxic nodular goitre tissue.

Animals↗

PubMed1990

Plasma exchange in endocrine ophthalmopathy.

We studied the effects of intensive plasma exchange on endocrine ophthalmopathy in 12 patients with Graves' disease and one with Hashimoto's thyroiditis. All patients were euthyroid at the time of plasma exchange. All but five had concomitant treatment with azathioprine. Each patient had a treatment period consisting of six plasma exchanges performed in 2-3 weeks; two patients were treated in two periods. Each time a mean of 2.4 liters plasma was exchanged. There was a prompt reduction in the concentration of circulating immune complexes and/or thyrotropin receptor antibodies following plasma exchange. Six of the 13 patients improved their proptosis; their median duration of eye symptoms before treatment was less than 8 months. In patients suffering from eye symptoms for more than 1 year improvement was rare. Overall the Hertel values were 24.1 +/- 4.4 (SD) before and 22.8 +/- 3.4 after plasma exchange for the left eyes (P = 0.07) and 23.8 +/- 4.0 before and 23.0 +/- 3.8 after for the right eyes (P = 0.09). Nine patients altogether improved their ophthalmopathy index and periorbital oedema. In patients with disabling endocrine ophthalmopathy plasma exchange may sometimes be of value to induce a relief of the ophthalmopathy; when it is used it should be instituted before fibrotic changes occur. We suggest that concomitant immunosuppressive drugs should be given to prevent rebound phenomenon induced by plasma exchange. To establish the role of plasma exchange in the treatment of endocrine ophthalmopathy controlled studies should be performed.

Adult↗

PubMed1988

Serum free thyroid hormones are decreased by betamethasone treatment in Graves' disease.

38 patients with Graves' disease were treated at random with the glucocorticosteroid betamethasone or with placebo. The daily oral dose was 6.0 mg for the first 5 days, 4.5 mg for the following week, and then 3.0 mg. The serum free triiodothyronine (FT3) concentration decreased within 5 days, while the free thyroxine (FT4) level was reduced first after 3 weeks of betamethasone treatment. The suppressed serum thyrotropin concentration did not change. In the placebo group no significant constant alterations were found in any of the variables studied. The results corroborate that betamethasone decreases FT3 and to a less degree also FT4, which earlier has been indicated by indirect methods, although the mechanisms behind the changes remain to be clarified. Since FT3 is more readily available for the metabolic effects in tissues the rapid striking fall in its concentration is an argument for glucocorticoid treatment in selected patients with severe hyperthyroidism of Graves' disease.

Adult↗

PubMed1987

Effect of therapy on the serum thyroglobulin concentration in patients with toxic diffuse goiter, toxic nodular goiter and toxic adenoma.

Serum thyroglobulin (S-Tg) was measured in 104 patients with thyrotoxicosis, 59 of whom had toxic diffuse goiter (Graves' disease), in 30 with toxic nodular goiter and in 15 with toxic adenoma. Before treatment, most patients had increased S-Tg concentrations, regardless of what type of thyrotoxicosis they had. After therapy the course of the S-Tg varied, two major patterns being observed: the S-Tg concentration increased in some patients but decreased in others, although no relationship could be found between these patterns and the outcome of therapy, the presence or absence of thyroglobulin antibodies (Tg-ab) or changes in the Tg-ab titer. However, the median pretreatment concentrations of S-Tg were significantly higher in patients with toxic nodular goiter and toxic adenoma than in those with toxic diffuse goiter (p less than 0.001 and p less than 0.05, respectively), but did not differ significantly between patients with toxic nodular goiter and toxic adenoma. The lowest posttreatment S-Tg concentrations were found after surgery, irrespective of type of thyrotoxicosis. The median pretreatment and posttreatment S-Tg concentrations in patients with toxic diffuse goiter who relapsed, did not differ from those patients in remission. This was also true of patients with toxic nodular goiter. In both groups, however, there was a tendency towards higher pretreatment S-Tg values in patients who subsequently relapsed. Serial determinations of S-Tg, on the other hand, are of limited value in predicting the risk of recurrence, independent of which type of thyrotoxicosis is involved.

Adolescent↗

PubMed1987

Effects of thyroid stimulating immunoglobulin on function and morphology of xenotransplanted toxic diffuse, toxic nodular and normal thyroid tissue.

In order to examine the properties of human thyroid tissue, toxic diffuse goiter (TDG), toxic nodular goiter (TNG) and normal thyroid tissue were transplanted to nude mice. Starting 3 and 10 weeks after the transplantation the mice were given 14 daily injections of control serum or serum containing thyroid stimulating immunoglobulin (TSI). The uptake and release of 125I were repeatedly measured externally. The uptake and unstimulated release of 125I was lowest in TDG transplants, highest in TNG transplants, and intermediate in transplants of normal thyroid tissue. The findings were similar at both 3 and 10 weeks. Injections of TSI reduced the biological half-time of the tracer in TDG and normal transplants, but had no significant effect on TNG transplants. Light and electron microscopic studies showed that hyperplastic TDG tissue underwent involution after transplantation, whereas TNG and normal thyroid tissue remained unchanged. Injection of TSI reactivated TDG tissue; morphometry showed that the absolute and relative volumes of the follicle cells were more than doubled, with a corresponding decrease in the volume of the follicle lumen, and mitotic figures were common. Similar findings were seen in normal transplants, whereas the effect of TSI on TNG tissue was less pronounced. In summary, our observations show that serum from a patient with Graves' disease stimulated iodine release and induced follicle cell hyperplasia and probably also follicle cell multiplication in transplanted normal and TDG tissue, but had a lesser effect on TNG tissue.

Animals↗

PubMed1987

Graves' IgG stimulates thyroid epithelial cell proliferation in xenotransplanted human toxic diffuse goitre.

Human toxic diffuse goitre tissue was xenotransplanted to athymic mice. Transplant function was analyzed as 18 h [125I]thyroid transplant uptake at day 21 and at 10 weeks after transplantation. Graves' IgG or normal IgG was given ip daily day 22-35. Epithelial cell proliferation in the thyroid transplants was analyzed by continuous [3H]thymidine administration for 12 days between day 28 and 39 in a separate series given Graves' or normal IgG daily during the same period. The 18 h transplant uptake increased 12.8 times from 3 to 10 weeks in the Graves' IgG group but only 3.6 times in the controls (P less than 0.05). The fraction of labelled cells after [3H]thymidine incorporation was 51% +/- (SEM) after parallel Graves' IgG administration but only 2 +/- 0.3% (P less than 0.002) in the controls. The increased 10 weeks iodide uptake after Graves' IgG may be explained by an increased vascularisation or capillary maturation, by an increased individual cell sensitivity to stimulation or by an increased number of cells. Our results indicate that serum from patients with toxic diffuse goitre, i.e. Graves' IgG, contains a factor which promotes thyroid epithelial cell proliferation. Whether this is identical to TSI or is another IgG fraction remains to be shown.

Animals↗

PubMed1986

Effects of betamethasone on serum iodothyronines and thyroid hormone-binding proteins in Graves' disease.

The influence of betamethasone on iodothyronines and their binding proteins in serum was studied in 18 patients with Graves' disease. Betamethasone, 6 mg daily, was given orally for 5 days. Serum triiodothyronine (T3) concentration decreased, reverse triiodothyronine increased, while thyroxine (T4) and thyroid-stimulating hormone were unchanged. Thyroxine-binding globulin (TBG) decreased and thyroxine-binding prealbumin increased. In accordance with the decrease in TBG, the in vitro T3 uptake increased and out of the indirect measures of the free thyroid hormones, the free T4 index increased and the free T3 index decreased. We suggest that the decrease in serum T3 during betamethasone administration supports the view of glucocorticoids being beneficial as additional treatment in some patients with thyrotoxic crisis.

Adult↗

PubMed1986

"The low T3 syndrome" and impaired thyroid protein synthesis in experimental trauma.

The thyroid response was evaluated in the present trauma model. Trauma of varying severity was studied in 3 groups of anesthetized pigs. The animals were exposed to preparative surgery alone (n = 6) or followed by a standardized missile trauma to a hind leg (n = 10) or to the abdomen (n = 8). Post-trauma observation for 24-48 hours under continuous anesthesia included measurements of circulating T4, T3 and rT3. The serum concentrations of T4 and T3 fell significantly in all groups, the fall being exponential in the missile trauma groups. The reductions were greatest in the most severely injured group (abdominal trauma) and least in the group with preparative surgery only. The nadir of T4 concentration was reached at 24 hours in all groups. The T3 nadir occurred at 12 hours in the abdominal trauma group and at 24 hours in the groups with hind-leg trauma and preparative surgery. The rT3 concentration was significantly increased in the missile trauma groups. Thyroid protein synthesis was analysed in vitro by incubating thyroid tissue from pigs with missile trauma (n = 9) or with preparative surgery (n = 6). The 3H-leucine incorporation into the soluble thyroid proteins, measured as DPM/DNA, was 35% lower after missile trauma than after preparative surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Influence of extradural blockade on serum thyroid hormone concentrations after surgery.

To study the changes in thyroid hormone metabolism after surgery, the influence of neurogenic blockade by extradural local anaesthetics, and possible hormonal interactions, 16 women undergoing cholecystectomy were randomly allocated to two groups of eight each. All patients received general anaesthesia and in addition one group received extradural blockade for 24 h. Preoperatively and at 2, 4, 6, 12 and 24 h after skin incision arterial serum concentrations of thyroid hormones (T3, free T3, rT3, T4, free T4 and TSH), catecholamines (adrenaline and noradrenaline), cortisol and serum proteins (albumin, prealbumin and TBG) were determined. In both groups total T3, free T3, total T4 and TSH decreased significantly whereas free T4 was unchanged and rT3 increased. No differences between the extradural group and the controls regarding thyroid hormones were observed, in spite of suppressed catecholamine and cortisol concentrations in the extradural group as compared to the control group. All serum thyroid hormone binding proteins decreased significantly in both groups. Changes in thyroid hormone metabolism after surgery seem independent of neurogenic blockade by extradural local anaesthetics, and of plasma catecholamine and cortisol concentrations.

Adult↗

PubMed1984

Ultrastructural morphology and evidence of iodide uptake and protein synthesis in normal human thyroid transplants in nude mice.

Normal human thyroid tissue was xenotransplanted to athymic mice. Well preserved structural properties of the transplants were observed at both light and electron microscopical level. Analysis of the soluble proteins in the transplants by polyacrylamide gel electrophoresis showed that the major fractions were the 19S thyroglobulin, the 27S iodoprotein and a larger protein fraction. Protein synthesizing capacity of the transplants, as measured by in vivo 3H-leucine incorporation into the soluble transplants proteins was demonstrated. The observed 3H-leucine incorporation was in the same magnitude as that found in the original donor tissue at the time of transplantation. Four weeks after transplantation a significant 125I-iodide uptake (2.0%) was observed in the transplants. Corresponding value for the host thyroids was 6.6%. The biological half-time of the accumulated 125I-iodide in the transplants was reduced from 97 days to 38 days between 2 and 4 weeks after transplantation. The biological half-time in the host thyroid increased from 27 days to 32 days during the same period. This investigation shows that normal human thyroid tissue can be transplanted to nude mice with preserved tissue organisation and maintained cellular function.

Animals↗

PubMed1984

Serum thyroglobulin in differentiated thyroid carcinoma.

Serum thyroglobulin (S-Tg) concentrations were measured in 262 patients with differentiated thyroid carcinoma. Analysis of S-Tg with respect to histology showed that the follicular variety of carcinoma had the highest S-Tg values preoperatively and postoperatively when metastases were found. The S-Tg levels during thyroxine treatment accurately predicted the results of 131-I total body scan in all but two cases. In another patient both S-Tg and total body iodine scan were negative at the time when metastases were discovered at X-ray examination. All but two patients with negative scan had S-Tg less than 10 micrograms/l, whereas patients with metastases had values between 11 and greater than 5000 micrograms/l. In patients with residual thyroid bed uptake the S-Tg range was from less than 2 to 84 micrograms/l. The authors conclude that determination of the S-Tg level can replace total body iodine scan in most patients who have undergone ablative therapy for differentiated thyroid carcinoma.

Adolescent↗

PubMed1984

Thyroid hormones, catecholamine and cortisol concentrations after upper abdominal surgery.

Serum and plasma concentrations of thyroid hormones, catecholamines and cortisol as well as oxygen consumption were measured simultaneously in twenty patients in connection with cholecystectomy. Arterial blood samples were taken before surgery and at 2, 24, 48, 72 and 96 h after skin incision. A marked and prolonged decrease in T3 and free T3 concentrations was seen. A minor decrease in T4 was also observed but free T4 remained unchanged. TSH concentration was increased 2 h after skin incision, but at no other occasion. A marked increase in adrenaline and noradrenaline concentrations was observed 2 h after the start of surgery. This increase lasted 24 h for noradrenaline. There was a marked and prolonged rise in plasma cortisol after surgery. The oxygen uptake was higher than the preoperative value during the entire postoperative period. No correlations between thyroid hormones and catecholamines or cortisol or oxygen uptake were found. It is concluded that the most pronounced changes in thyroid hormones and TSH after upper abdominal surgery occur about 24 h postoperatively but catecholamines demonstrate their maximal increase immediately after surgery. The inverse correlation between T3 and catecholamines previously reported in burned patients, with their severe hypermetabolism, it is not present during the moderate hypermetabolism after abdominal surgery.

Abdomen↗

PubMed1983

Thyroid hormone secretion rates: response to endogenous and exogenous TSH in man during surgery.

The thyroid hormone secretory response to TSH was studied in twenty-eight patients undergoing thyroid and parathyroid surgery. Eighteen patients received bovine or human exogenous TSH by injection into a thyroid artery, and 10 received TRH to stimulate endogenous TSH secretion. Thyroid secretion rates of T4, T3, and rT3 were determined directly from measurement of blood flow and the hormone gradient across the gland. A significant secretory response was seen for all three hormones following TSH increase. T3 secretion accelerated more rapidly than that of T4 and rT3, thus reducing the T4/T3 and rT3/T3 ratios. The T4/rT3 ratio fell during the first 30 min but then increased. The responses correlated with the area under the curve of the TSH serum concentration, and were similar after administration of bovine and human exogenous TSH, and TRH. Conclusions regarding preferential secretion ought to be made by comparing ratios of thyroid hormone secretion with those of the hormone content of the gland, but our results indicate that TSH induces preferential secretion of triiodothyronines in man.

Adult↗

PubMed1982

Influence of hyperthyroidism on the kinetics of methimazole, propranolol, metoprolol and atenolol.

The kinetic profiles of oral methimazole 40 mg, propranolol 80 mg, metoprolol 100 mg and atenolol 100 mg were compared in hyperthyroid patients both during the hyper- and euthyroid states. for methimazole, neither the peak concentration (Cmax), the time to reach peak concentration (tmax), the elimination half-life (t 1/2) nor the area under the curve (AUC) value was affected by the hyperthyroid state. For propranolol and metoprolol, which undergo extensive presystemic clearance, the AUC values were lower (p less than 0.02) when the patients were hyperthyroid than when they had become euthyroid, but the t 1/2's were not significantly altered. For atenolol, there were no significant kinetic differences between the hyperthyroid and euthyroid states. The findings are compatible with the assumption that hyperthyroidism does not affect the kinetics of methimazole or atenolol, but that it may enhance presystemic clearance of propranolol and metoprolol.

Administration, Oral↗