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Biomedical subjects

M Hüfner

Publications and source records attributed to M Hüfner.

At least 73 records · Page 4Linked to original sources

Peripheral effects of thyroid hormones: alteration of intracellular Na-concentration, ouabain-sensitive Na-transport, and Na-Li countertransport in human red blood cells.

To investigate the effect of thyroid hormones on erythrocyte cation transport systems and intracellular electrolyte content we have measured the activity of Na-K ATPase, Na-Li countertransport, as well as red cell sodium and potassium contents in patients with hyperthyroidism and in euthyroid controls. Intracellular Na- and K-concentrations were determined in erythrocytes washed three times in isotonic MgCl2 solution. Ouabain-sensitive Na-transport was estimated as the increase of Na before and after addition of ouabain in an erythrocyte suspension in isotonic Na-free medium. Na-Li countertransport was measured according to the method described by Canessa et al. [2]. The patients with hyperthyroidism exhibited a significantly elevated intracellular sodium content as well as a highly increased Na-K ATPase activity. Intracellular potassium content was not altered in the hyperthyroid subjects, but Na-Li countertransport was markedly decreased as compared to the controls. The results indicate that different ion transport systems of the erythrocyte membrane are influenced by thyroid hormones. We suggest that the elevation of Na-K ATPase activity might be due to the increased intracellular sodium concentration which is caused by the diminished countertransport pathway. Furthermore, the activity of Na-K ATPase, Na-Li countertransport, and intracellular sodium content in erythrocytes might be a useful peripheral indicator of thyroid hormone excess.

Biological Transport, Active↗

[Long-term observation of 15 patients with differentiated thyroid cancer and elevated plasma thyroglobulin levels of unclear origin].

The follow-up of 15 patients with differentiated cancer of the thyroid was analysed retrospectively. All patients had persistent or developed elevated thyroglobulin (Tg) plasma levels (greater than 10 ng/ml) after total thyroidectomy and 131 I therapy. There was no evidence of thyroid remnants or metastases in the 131 I whole body scan, bone scan, chest X-ray or clinical investigation. Nine of 15 patients developed local or distant metastases during a follow-up period of 3-39 months (mean = 18 months). Only one of seven recurrences tested were 131 I positive, Tg values of 9 from 12 patients showed no correlation to the Thyroid-stimulating hormone (TSH) level. It is concluded that: (1) this group of patients is at high risk of developing a recurrence (2) new methods have to be developed for the localization of 131 I negative but Tg positive metastases.

Adenocarcinoma↗

Radioimmunoassay for serum thyroglobulin designed for early detection of metastases and recurrencies in the follow-up of patients with differentiated thyroid carcinoma.

A radioimmunoassay (RIA) for the measurement of thyroglobulin in human serum was developed and factors that influence sensitivity were investigated. In a comparison of 3 different labeling procedures (chloramine T, iodogen, lactoperoxidase) iodogen-prepared tracer proved to be slightly superior with respect to sensitivity and stability. The shelf life of the tracer was improved by a protein-enriched buffer, which serves as a radical scavenger. The binding kinetics of tracer to antibody at different temperature ranges were examined, and the most rapid and complete binding was found at room temperature. For the preparation of standard curves, several artificial media were compared with thyroglobulin-free serum. Second antibody separation was investigated and optimized. By employing sequential saturation, sensitivity of 0.75 microgram/1 (B0-3 SD) and 50% intercept of less than 5 micrograms/l were achieved. The results of RIA measurements of thyroglobulin in 142 patients with papillary and follicular thyroid carcinoma after thyroidectomy and 131I treatment were compared with 131I whole-body scans. The results confirmed that serum thyroglobulin is an early indicator of recurrency.

Adenocarcinoma↗

[Diagnostic value of 131I-whole body scintigraphy in the after care of differentiated thyroid cancer].

The value of scintiscanning after treatment and of routine control scanning in differentiated thyroid carcinoma was evaluated in a retrospective study for the diagnosis of metastases and recurrencies. Scintigrams after treatment detected 76% of all metastases at the time of primary treatment. In contrast, only 4 (18%) out of 22 late relapses were positive in the radioiodo-scintigram. Three of these had been diagnosed earlier already on clinical grounds. Thus, routine whole-body scintigrams using 2 mCi 131I for the after-care of differentiated thyroid carcinoma is without relevant benefit for patients, and certainly not if an aggressive treatment concept has been followed from the beginning. Whole-body scintigraphy should be used only in exceptional cases. Follow-up care should be based on regular thyreoglobulin assessment using a sensitive and controlled method.

Aftercare↗

A comparison of the effectiveness of 131I whole body scans and plasma Tg determinations in the diagnosis of metastatic differentiated carcinoma of the thyroid: a retrospective study.

In 68 patients with proved metastases of differentiated thyroid carcinoma the comparative value of the 131I whole body scan and plasma Tg measurements in establishing the diagnosis of metastasis or recurrence was analyzed retrospectively. At the time of primary therapy most metastases were diagnosed by the post-therapy scan (78%). Eight of 9 scintigraphic negative metastases in the post-therapy scan were indicated by elevated Tg levels (greater than 10 ng/ml). Twenty-four of 28 recurrences after a disease free interval were negative in the 2 mCi 131I scan, 18 of these patients were Tg positive. Of the 4 recurrences with positive 131I uptake all were Tg positive; two of them only during endogenous TSH stimulation. It is concluded that the routine 2 mCi whole body scan is less efficient in follow-up than is generally assumed. The most important follow-up parameter for these patients is the plasma Tg which can be obtained under suppressive therapy if a sensitive assay is used. In patients with a negative post-therapy scan and a negative Tg (less than 5 ng/ml) it seems justified to omit further 131I whole body control scans as long as Tg remains negative.

Carcinoma↗

Homologous radioimmunoassay for human parathyrin (residues 53-84).

We describe a sequential saturation double-antibody radioimmunoassay for carboxyl-terminal fragments of human parathyrin (hPTH) in serum. Standards are prepared with synthetic hPTH (residues 53-84) in hPTH-free serum. Antisera are obtained by immunizing guinea pigs with partly purified hPTH extracted from adenomatous glands. Tracer is prepared by labeling hPTH (53-84), presumably at the histidine residue, with 125I by the Chloramine T method at pH 8.6. Dilution curves for hPTH extracted from adenomas are superimposable on dilution curves for the synthetic 53-84 fragment. Dilution of sera from hyperparathyroid patients showed linearity of response with concentration in the present assay, but non-linearity in the heterologous radioimmunoassay. In contrast to the heterologous system, which discriminated 28 of 32 patients with primary hyperparathyroidism from 32 normals (normal range: undetectable to 54 pmol/L, omitting the highest and lowest values from controls), the present assay separated these groups without overlap.

Calcium↗

[The value of serum thyroglobulin determination in the after-care of patients with differentiated thyroid neoplasms].

Plasma thyroglobulin (Tg) was determined by radioimmunoassay in 219 patients with differentiated carcinoma of the thyroid gland after treatment by total thyreoidectomy and at least 2 131I therapies with a total of 170 mC. Of 145 patients without residual thyroid tissue and a negative whole body scan, 6 patients exhibited significant Tg levels. It remains unclear whether these individuals will develop recurrency later on. Of 23 patients with proven metastases, 14 had extremely high Tg concentrations of greater than 1000 ng/ml. In 6 cases Tg was between 20 and 280 ng/ml and in 3 individuals Tg levels below 10 ng/ml were measured. The reason for low Tg concentrations in some patients with proven metastases is unknown. At present plasma Tg measurements therefore cannot be recommended as substitution for whole body scanning. However, plasma Tg is an important additional parameter in the follow-up of patients with differentiated carcinoma of the thyroid.

Adenocarcinoma↗

[Thyreotrophic hypophysial function after surgery for euthyroid goiter or autonomous adenoma].

44 euthyroid patients with nodular goiter and 23 patients with autonomous adenomas were treated by hemithyrectomy or subtotal thyrectomy. Thyroid function was followed over 6 weeks post-operation by TRH tests, which were performed before and at the 5th, 14th, 28th and 42nd day after operation. Bilateral subtotal thyrectomized patients with euthyroid goiter showed a continous increase of basal and TRH stimulated TSH level into the hypothyroid range. 19 of 25 patients were hypothyroid 6 weeks after operation. In contrast, 14 of 19 hemithyrectomized patients with euthyroid goiters remained euthyroid during the time investigated; 5 patients showed a transient TSH increase into the hypothyroid range but were euthyroid again after 6 weeks. TSH levels obtained from patients operated for autonomous adenoma may not yet reflect thyroid function during the time interval investigated here. We conclude that all patients with euthyroid goiter after bilateral subtotal thyrectomy should receive hormone substitution because they are at high risk to develop recurrency. However, we propose that in patients hemithyrectomized for euthyroid goiters the decision of long term hormone substitution should be cased on the result of a TRH-test 3--4 month after operation. Substitution with thyroid hormone should be preferred to iodide because it is unclear yet how far a failure in iodide organification and hormone synthesis is the reason for goiter recurrency.

Adenoma↗

Studies on the deiodination of 3,3',5'-T3 (reverse T3) to 3,3'-T2 (diiodothyronine) in rat liver.

Properties of the deiodination reaction of rT3 to 3,3' T2 in rat liver homogenate are reported and compared with T4 to T3 conversion under similar conditions. pH optimum and SH-group dependency of these two reactions are quite different, though both are concerned with 5' deiodination. The most potent activator of the reaction rT3 to T2' is dithiothreitol; the enzyme activity increases almost linearly even at very high concentration of this compound (the same is true for mercaptoethanol). Glutathione and coenzyme A, show only small activating effects. T4 to T3 and rT3 to T2' converting is being induced almost parallel in thyrectomized rats substituted with T4 or T3.

Animals↗

Radioimmunoassay for 3,3'-diiodothyronine in human serum.

A specific radioimmunoassay for measurement of 3,3'-diiodothyronine (T2') is presented. With the method described (ethanol extraction of native serum and lyophilisation of the extract) the application of 400 microliter serum equivalent in the assay is possible. Standards and sera are treated similarly. The detection limit is 0.625 ng/dl, comparison between direct assay and dried extract assay shows good correlation. Mean normal T2' serum concentration in man is 7.2 ng/dl (range 3 to 11 ng/dl), hypothyroid: below 3.0 ng/dl, hyperthyroid: 11-64 ng/dl (range). T2' level in cord-blood of newborns: 16.5 ng/dl. The urinary excretion of free T2' of normal man is 0.49 microgram/24 h (mean), a relatively high excretion rate in comparison to the low serum level.

Adult↗

Investigations on the deiodination of thyroxine (T4) to 3,3'-diiodothyronine (3,3'-T2) in rat liver homogenate.

Properties of an inactivating pathway of T4 to 3,3'-diiodothyronine (T2') in rat liver homogenate are described. The intermediate product (of this reaction sequence) is reverse T3 (rT3) which is very labile and cannot be measured at pH 7.5. The apparent KM of the reaction rT3 to T2' is 2 X 10(-8) M. The activities catalyzing the reactions T4 to T3, T4 to T2' and rT3 to T2' are found in the 100 000 X g pellet. Propylthiouracil inhibits all three activities to a similar degree; alpha-methyl-p-tyrosine has no effect. T3 seems to be only a minor source of T2' production. The molar ratio of the two T4 deiodination pathways T4 to T3/T4 to T2' under these conditions is about 1.7; however, by changing the pH this ratio could be significantly altered.

Animals↗

Radioimmunoassay for parathyrin. Characterization of six different antigens and antisera.

We studied six different antisera to bovine or porcine parathyrin (parathyroid hormone, PTH), produced in rabbit, guinea pigs, sheep or goat, two of which are commercially available. The antisera were characterized with regard to species specificity, affinity and their ability to identify patients with primary hyperparathyroidism. In this heterologous radioimmunoassay system in which [125I]parathyrin is used as a tracer, some cross-reactivity of the antisera to the hormone or hormone fragments present in human serum was demonstrated. However, there is some overlap of serum immunoreactive parathyrin in patients with or without primary hyperparathyroidism. The results of this and other studies illustrate the necessity for a homologous radioimmunoassay for human parathyrin.

Animals↗

Correlation of reverse-T3 and 3,3'-T2 (T2') plasma concentrations under physiological and experimental conditions in man.

T2' plasma levels are measured under different conditions and correlated to the repective rT3 concentrations. Specific RIAs for T2' and rT3 are used. Pharmacological doses of T3 cause an increase of plasma T2'; if T3 or T4 doses are administered to an athyroid patient which cause a similar level of plasma T3 the increase of T2' is much larger during T4 treatment. Cord blood levels of T2' are 2--3-fold higher than in normal adults whereas rT3 concentrations are about 10 times higher than normal. After birth rT3 and T2' levels decrease in about a parallel manner. After a bolus iv injection of 500 microgram rT3, T2' starts to increase as early as 2 min after injection. PTU in therapeutic doses causes a rapid increase of plasma rT3 with a maximum 4 h after ingestion. A dose of 150 mg PTU causes a maximum of about 100% above baseline. T2' also increases but to a lesser degree (about 50% above baseline). We conclude that rT3 is a most important precursor of T2' whereas T3 contributes only to a minor degree to the total T2' production under physiological conditions.

Adult↗

[Plasma levels of 3,3', 5'-T3 (reverse-T3) under various functional thyroid conditions].

Reverse T3 (r-T3) was measured in unextracted human plasma under different clinical conditions. The mean normal concentration was 0.20 ng/ml. In thyreotoxic patients r-T3 was elevated in the majority of the cases, however, it was normal in three cases of T3-toxicoses. Thyrectomized patients during different hormon substitution showed r-T3 levels corresponding to the T4 concentrations measured. Patients with severe chronic illnesses and low T3 showed normal to considerably elevated r-T3 levels. According to these results r-T3 is not of additional value in the diagnosis of thyroid disorders.

Hyperthyroidism↗

[Approach to a differentiated recurrence prevention following struma surgery].

Changes of the pituitary-thyroid axis were studied in 70 patients (45 with euthyroid goiters, 25 with autonomous adenomas) preoperatively; over a 6-week postoperative interval without thyroid-hormone treatment; under T4 therapy increased stepwise and maintained for 1 year; and over a period of 12 weeks after its withdrawal. The postoperative thyrotropic function obviously depends on the preoperative condition and thereby on the quality of the remaining tissue as well as on the extent of the operation and thus the amount of remaining tissue. The frequency of a "prehypothyroid" status in the early postoperative course is high (77%) after bilateral resection for euthyroid goiter, but decreased 1 year after the operation (47%). After unilateral resection for euthyroid goiters and after bilateral and unilateral resection or enucleation for autonomous adenomas, the remaining tissue is for the most part sufficient to avoid increased pituitary stimulation. Prophylaxis of recurrent goiter with thyroid hormones could be prescribed individually on the basis of the postoperative function of the pituitary-thyroid axis.

Adenoma↗