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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 54 (1976), S. 987-993 
    ISSN: 1432-1440
    Keywords: Thyroid Diseases ; Immunology ; Schilddrüsenerkrankungen ; Immunologie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung T-Lymphocyten wurden bei 18 Patienten mit unbehandelter florider Hyperthyreose, 28 Patienten mit „kompensierter Hyperthyreose“ nach thyreostatischer Langzeitbehandlung mit Carbimazol oder Methimazol in Kombination mit L-Thyroxin, 14 Hyperthyreosen nach 131-Jodbehandlung, 7 Hashimoto-Thyreoiditiden und 7 blanden Strumen bestimmt und mit einem Normalkollektiv von 40 Schilddrüsengesunden verglichen. Ein Unterschied des prozentualen Anteils und der Absolutzahlen der T-Lymphocyten ließ sich weder zwischen den Gruppen mit Schilddrüsenerkrankungen noch im Vergleich zum Normalkollektiv sichern. Nach diesen Befunden sind die Absolut- und Relativwerte der T-Lymphocyten im Blut keine geeigneten Parameter für die Beurteilung der Aktivität und Prognose der verschiedenen Schilddrüsenerkrankungen und gestatten keine Aussage über die pathogenetisch vielleicht relevante Bedeutung der zellvermittelten Immunität.
    Notes: Summary Thymus-derived peripheral blood lymphocytes were studied in untreated (n=18), methimazoletreated (n=28) thyrotoxicosis, after radioiodine (n=14), in Hashimoto thyroiditis (n=7) and in euthyroid goiter (n=7). The results were compared with normal persons (n=40) without thyroid disease. There was no significant difference in the total and relative counts of T-cells either between the different groups nor compared with the controls. These findings confirm that T-cells in peripheral blood cannot give any information about activity or prognosis of the various thyroid diseases. Thus T-cells give no further suggestion concerning the possible pathogenetic role of cell-mediated-immunity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 41 (1963), S. 337-338 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Zusammenfassung Bei 25 Schilddrüsenkranken und 20 gesunden Kontrollpersonen wird als Maßgabe des Vitamin B6-Stoffwechsels die Xanthurensäure-Ausscheidung im Harn untersucht. Vor der Belastung mit Tryptophan scheiden Schilddrüsenkranke wie-gesunde zwischen 4 und 9 mg Xanthurensäure im 24-Std-Harn aus. Nach der Belastung durch 10 g d,l-Tryptophan steigt bei 14 unbehandelten Hyperthyreotikern die mittlere Ausscheidung auf 53 mg, bei fünf anbehandelten Hyperthyreotikern nur auf 15 mg gegenüber den 17 mg der Kontrollpersonen an. Von 4 Hypothyreotikern scheidet nur 1 Patient vermehrt Xanthurensäure aus, 2 Patienten mit Schilddrüsen-Carcinom verhalten sich normal. Die Befunde weisen auf einen relativen Vitamin B6-Mangel bei Hyperthyreosen hin, der bereits nach Anbehandlung mit Thyreostatica oder Radiojod vor Erreichen der euthyreoten Stoffwechsellage verschwindet.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 531-539 
    ISSN: 1432-1440
    Keywords: Antithyroid drugs ; Methimazole ; Carbimazole ; Propylthiouracil ; Pharmokinetics ; Absorption ; Metabolism ; Excretion ; Placental Transfers ; Pregnancy ; Thyreostatika ; Methimazol ; Carbimazol ; Propylthiouracil ; Pharmakokinetik ; Resorption ; Metabolismus ; Exkretion ; Plazentapassage ; Schwangerschaft
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Untersuchungen der Pharmakokinetik von Thyreostatika sind durch das Fehlen einfacher und empfindlicher Bestimmungsmethoden für diese Pharmaka in biologischen Flüssigkeiten erschwert. 2. Die Resorption von Carbimazol und — besonders — Methimazol ist erheblichen interindividuellen Schwankungen unterworfen. 3. Propylthiouracil, aber nicht Methimazol wird an Plasmaproteine gebunden. 4. Nach Gabe von Carbimazol ist nur Methimazol im Serum, Urin und Schilddrüsengewebe nachweisbar. Die Konversion von Carbimazol zu Methimazol scheint enzymatisch gesteuert zu werden. Die Methimazol-Plasmaspiegel sind nach Gabe von Carbimazol niedriger als nach Gabe einer gleichen Menge von Methimazol. 10 mg Carbimazol sind äquivalent zu 6–7 mg Methimazol. 5. Verteilung und Elimination von Methimazol und Propylthiouracil können durch ein Ein-Kompartment-System mit Eliminationsweg 1. Ordnung beschrieben werden. Die Plasmahalbwertszeit von Propylthiouracil beträgt etwa 1 h, die von Methimazol 2–6 h. 6. Thyreostatika werden in der Schilddrüse angereichert. Diese Anreicherung wird bei Labortieren durch Jodmangel gehemmt. Die Hemmung der Jodidorganifikation hängt mehr von der intrathyreoidalen als der Plasmakonzentration der Thyreostatika ab. 7. In der Schilddrüse werden die Thyreostatika schrittweise oxidiert und teilweise an Thyreoglobulin gebunden. Der Hauptmetabolit von PTU ist PTU-SO2H. Ein Methimazolmetabolit, das Methylthiohydantoin, kann im Plasma und im Urin nachgewiesen werden. 8. Propylthiouracil wird rasch an Glucuronsäure gekoppelt. Ein beträchtlicher Teil der Thyreostatika und ihrer Metabolite wird mit der Galle ausgeschieden und später reabsorbiert (enterohepatischer Kreislauf). Die faekale Ausscheidung ist sehr niedrig. Im Urin erscheinen geringe Mengen der nicht metabolisierten Substanzen zusammen mit Glucuroniden, Methylderivaten (nur bei Propylthiouracil) und unidentifizierten Metaboliten. 9. In der Schwangerschaft ist die Halbwertszeit von Methimazol verkürzt (nach vorläufigen Daten). Methimazol und Propylthiouracil durchqueren die Plazentaschranke und können im fetalen Blut und in der fetalen Schilddrüse nachgewiesen werden. Die Konzentrationen in der Muttermilch sind sehr gering, besonders bei Propylthiouracil. 10. Über die Änderungen der Thyreostatika-Pharmakokinetik während der Behandlung einer Hyperthyreose gibt es bisher nur unzureichende Daten.
    Notes: Summary Studies of antithyroid drug pharmacokinetics suffer from the lack of simple and sensitive methods for the measurement of these drugs in biologic fluids. This is reflected by most of the data available at present. From a critical review of these studies, the following conclusions emerge: 1) Absorption of methimazole and carbimazole is subject to considerable interindividual variability, which is more pronounced for methimazole than for carbimazole. 2) Propylthiouracil, but not methimazole, is bound to plasma proteins. 3) After administration of carbimazole, only methimazole can be detected in serum and thyroid tissue. Conversion of carbimazole to methimazole appears to be an enzymatic process. Methimazole plasma levels are lower after carbimazole administration than after equal amounts (on a weight basis) of methimazole; 10 mg carbimazole are equivalent to 6–7 mg methimazole. 4) Methimazole and propylthiouracil plasma levels decrease with time according to first-order kinetics. Serum half-life of propylthiouracil is about 1 h, half-life of methimazole is 2–6 h. 5) Antithyroid drugs are concentrated by the thyroid gland. This accumulation is inhibited in iodine deficiency in animals. Inhibition of iodide organification is dependent on intrathyroidal rather than plasma concentration of antithyroid drugs. 6) Intrathyroidal metabolism of antithyroid drugs involves binding to thyroglobulin and stepwise oxidation. The main metabolite of propylthiouracil is PTU-SO2H. A metabolite of methimazole, methylthiohydantoin, can be detected in plasma and urine. 7) Propylthiouracil is rapidly coupled to glucuronic acid. A significant proportion of antithyroid drugs and their metabolites is excreted into bile and later reabsorbed (enterohepatic circulation). Fecal excretion is very low. In urine, small amounts of unchanged drugs are excreted together with glucuronides, methyl derivatives (only PTU) and unidentified metabolites. 8) In pregnancy, methimazole half-life appears to be shortened. Methimazole and propylthiouracil can cross the placenta and are detected in the fetal circulation and thyroid. Concentrations in breast milk are very low, especially for propylthiouracil.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 681-686 
    ISSN: 1432-1440
    Keywords: Prednisone ; Prednisolone ; Adrenal insufficiency ; Prednison ; Prednisolon ; Nebennierenrindeninsuffizienz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 16 Patienten mit Nebennierenrindeninsuffizienz und nach bilateraler Adrenalektomie wurde Prednisolon im Serum und im Urin nach peroraler und intravenöser Gabe von Prednison und Prednisolon gemessen. Dabei sollten pharmakokinetische Daten über das Verhalten von Prednisolon gewonnen werden und die Frage geklärt werden, wie lange die Substanz nachweisbar ist. Da sich Prednisolon ähnlich wie Cortisol an Transcortin und Albumin bindet, konnte wegen des Fehlens endogener Corticosteroide eine einfache Proteinbindungsmethode zum Nachweis angewendet werden. Die Ergebnisse zeigen keinen signifikanten Unterschied in den Serumspiegeln nach oraler Gabe von Prednison oder Prednisolon. Die höchsten Konzentrationen wurden nach 2–3 h erreicht und betrugen nach 5, 7,5 und 10 mg Prednison 11,9±2,2 bzw. 15,9±3,4 und 21,5±5,9 µg/dl. Die Serumhalbwertszeit von ca 5 1/2 h läßt nach Gabe von entsprechend höheren Dosen noch auf das Vorkommen meßbarer Serumkonzentrationen nach 2 Tagen schließen. Da Prednisolon die meisten Meßmethoden für Cortisol beeinflußt, empfehlen wir, 2 Tage vor einer Cortisolbestimmung die Prednisontherapie abzusetzen. Die bei nebennierenrindeninsuffizienten Patienten ermittelte erniedrigte metabolische Clearancerate (56,0±7,2 1/24 h/m2) führen wir auf Alterationen im Corticoidstoffwechsel, möglicherweise bedingt durch eine erhöhte Transcortinproduktion, zurück.
    Notes: Summary Prednisolone was measured in serum and urine after oral and intravenous administration of prednisone and prednisolone in 16 patients with adrenal insufficiency and after bilateral adrenalectomy. Thus, the problem of cross-reactivity with endogenous steroids, the main factor disturbing the measurement of prednisolone, was completely eliminated. Prednisolone was detected by a simple competitive protein-binding radioassay. Distribution, elimination and other bioavailability parameters were calculated from the obtained data. No significant differences between serum levels were detected after oral administration of these drugs. Peak levels were reached after 2–3 h. After 5, 7.5 and 10 mg prednisone peak serum levels averaged 11.9±2.2, 15.9±3.4 and 21.5±5.9 µg/dl, respectively. Prednisolone was still detectable 24 h after administration of 10 mg. The plasma half-time of approximately 5 1/2 h suggests that prednisolone is present in serum far about 2 days after application of higher doses. Since prednisolone interfers in most assays for cortisol, prednisone therapie has to be stopped at least 2 days before cortisol determinations. Urinary excretion was proportional to the applicated doses. The metabolic clearance rate of prednisolone was decreased (56.0±7.2 1/24 h/m2) in patients with adrenal insufficiency. This can be attributed to alterations in corticosteroid metabolism, probably due to an increased transcortin production.
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  • 5
    ISSN: 1432-1440
    Keywords: Insulin-autoimmune syndrome ; Insulin autoantibodies ; Autoimmune disease ; Hypoglycemia ; HPLC ; Insulin receptor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 44-year old patient presented with recurrent hypoglycemic attacks after ingestion of carbohydrates. High insulin levels in the range of 350 µU/ml (normal range 〈20 µU/ml) were detected which rose to peak levels of 2,460 µU/ml (normal range 〈300 µU/ml) after oral glucose. The apparently high insulin concentrations were caused by insulin autoantibodies interfering in the radioimmunoassay (RIA) system (and thus with correct insulin quantitation).125I-insulin added to the patient's serum was not bound to dextrancoated charcoal but was precipitated with antihuman IgG serum. The antibodies bound human, porcine, and bovine insulin with similar affinity. Following Sephadex G-50 gel filtration, the patient's insulin eluted after the void volume. Free insulin was extracted from serum using Sep-Pak C18 cartridges and characterized by high pressure liquid chromatography (HPLC); it eluted similarly to synthetic human insulin. Quantitation of free insulin during a hypoglycemic attack (3.5 h after oral glucose, with a blood sugar of 20 mg/dl) showed an increased insulin level of 50 µU/ml. Insulin receptor concentration on erythrocytes was near the lower normal limit. We believe that the insulin antibodies present in this patient's serum (who supposedly never received insulin) led to the formation of a large circulating insulin pool, binding the insulin released after glucose stimulation, and causing hypoglycemias by delayed postprandial liberation of bound insulin.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 42 (1964), S. 736-740 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In homogenates of 18 euthyroid and 14 hyperthyroid resected goiters the activities of 20 enzymes were studied. The enzyme pattern in euthyroid goiters differed little from the one observed in normal thyroid glands. In contrast, in hyperthyroid goiters almost all enzyme activities were found significantly increased. A 10-times increment was observed for the thyroglobulin protease; cytochrome c-reductase, cytochrome c-oxydase, alkaline phosphatase, succinic dehydrogenase showed a 3 to 6-fold higher activity than the ones found in euthyroid goiters. The increase of activities are probably due to a true increment of enzymes rather than due to pretreatment or increased mass of tissue. Since all patients with hyperthyroidism were euthyroid according to B.M.R. at the time of operation the hypermetabolic state seems to be limited only to the thyroid tissue. No increased levels of enzyme activities were found in the serum and blood cell hemolyzates. The clinical improvement due to treatment does not seem to parallel the regulation of all hases of the metabolism.
    Notes: Zusammenfassung In Homogenaten von 18 euthyreoten und 14 hyperthyreoten Strumen, die operativ gewonnen worden waren, untersuchten wir die Aktivität von 20 Enzymen. Vor der Operation erfolgten Untersuchungen des Jodstoffwechsels und des Grundumsatzes. Die Enzymverteilung auf die einzelnen Zellfraktionen unterscheidet sich nicht von der in normalen Schilddrüsen. Das Enzymmuster in blanden Strumen unterscheidet sich kaum von demjenigen normaler Schilddrüsen. Dagegen sind die Aktivitäten aller Enzyme in hyperthyreoten Strumen erhöht. An der Spitze liegt die Thyreoglobulin-Protease mit einer Steigerung um das Zehnfache. Es folgen die Cytochrom-c-Reduktase, Cytochrom c-Oxydase, alkalische Phosphatase, Bernsteinsäure-Dehydrogenase mit einer drei- bis sechsfach höheren Aktivität als in blanden Strumen. Bis auf die Peptidase, TPNH- und DPNH-Glutathion-Reduktasen sind die gefundenen Unterschiede signifikant. Als Ursache der Aktivitätssteigerung kommt nicht eine Zunahme an Gewebsmasse oder der Einfluß der Narkose oder der präoperativ verwendeten Thyreostatica in Betracht, sondern ein Zuwachs an Enzymen als Ausdruck des besonderen Stoffwechsels der Drüse. Da alle Hyperthyreotiker zum Zeitpunkt der Operation euthyreot waren und einen normalen Sauerstoffverbrauch aufwiesen, scheint der Hypermetabolismus nur das Schilddrüsengewebe zu betreffen. Im Serum und Zellhämolysat von Hyperthyreotikern fanden sich normale Enzymaktivitäten. Hiernach scheint die klinisch beobachtete Besserung nicht mit der Regulation aller Stoffwechselvorgänge parallel zu gehen.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1440
    Keywords: Medullary thyroid carcinoma ; Prognostic factors ; Sporadic and familial form ; Age ; Sex ; Tumor stage at diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A retrospective study of 741 patients with medullary thyroid carcinoma diagnosed between 1967 and 1991 was carried out by members of the German Medullary Thyroid Carcinoma Study Group to evaluate prognostic factors. A total of 559 patients (75%) were considered to have sporadic disease, and 182 (25%) had the familial type. The sex ratio (male to female) was 1:1.4 in sporadic disease patients, and the mean age at diagnosis was 45.9 years (range 5-81 years). For familial disease patients the sex ratio was 1:1.1, and the mean age at diagnosis was 33.4 (range 5–77 years). The follow-up time for 630 patients ranged from 1 month to 20.8 years (mean 13.0 years). The overall adjusted survival rate was 86.7% at 5 years and 64.2% at 10 years. In a univariate analysis the stage of disease at diagnosis, age, sex, and type of disease (sporadic, familial) were relevant prognostic factors, with a better prognosis for young female patients with familial disease and diagnosed at an early stage. In a multivariate proportional hazards analysis, the difference in the survival rate of patients with familial disease versus those with the sporadic form disappeared, while prognostic information provided by age and sex was still significant. The poorer prognosis of patients with sporadic medullary thyroid carcinoma may be related to the patients' older age at detection and more advanced tumor stage at diagnosis. There seems to be no difference in biological behavior between tumors of the sporadic and those of the familial type.
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  • 8
    ISSN: 1432-1440
    Keywords: Soluble interleukin-2 receptors ; Type 1 diabetes ; Type 2 diabetes ; Prediabetes ; Autoimmune polyendocrinopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Interleukin-2 receptors are released in the circulation in response to antigenic or mytogenic stimulation of T-lymphocytes. Abnormal serum interleukin-2 receptor levels have been found in young children with type 1 diabetes and “prediabetes.” We measured interleukin-2 receptor levels in 17 patients with newly diagnosed type 1 diabetes, 21 patients with long-standing type 1 diabetes, 19 patients with long-standing type 2 diabetes, 19 islet-cell antibody positive nondiabetic polyendocrine patients, 12 islet-cell antibody-positive first-degree relatives of patients with type 1 diabetes and compared the results to age- and sex-matched normal controls. We found significantly lower interleukin-2 receptor levels in patients with newly diagnosed and long-standing type 1 diabetes compared to normal controls (87 ± 11 and 93 ± 11 vs. 142 ± 25 and 132 ± 40 U/ml, P 〈 0.001 and P 〈 0.01). There were no significant differences in interleukin-2 receptor levels between prediabetic groups and normal controls or patients with long-standing type 1 or type 2 diabetes. There was no correlation between glycosylated hemoglobin, blood glucose levels, and interleukin-2 receptor in the groups with long-standing type 1 or type 2 diabetes. We conclude that patients with type 1 diabetes have low interleukin-2 receptor serum levels. This phenomenon is acquired close to disease onset and is unlikely to be an early markers of type 1 diabetes.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 71 (1993), S. 547-551 
    ISSN: 1432-1440
    Keywords: Depot-bromocriptine ; Acromegaly ; Pregnancy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We studied the efficacy and tolerability of a repeatable long-acting parenteral depot-bromocriptine preparation (Parlodel LAR) in 14 acromegalic patients, 10 of whom had received oral bromocriptine therapy previously, 2 of them showing intolerance to oral bromocriptine. Patients received i.m. injections of 50–100 mg depot-bromocriptine at 4-week intervals for 3–24 months (median 6). Growth hormone profiles were assessed by four daily samples at 4-week intervals. Main daily growth hormone levels decreased from 52.1 ±12.3 μg/l (mean ± SEM) to 19.4 ± 4.7 μg/l on the day of injection. In 6 patients, growth hormone values were lowered by more than 50%, whereas IGF-I levels decreased only slightly and growth hormone values during the oral glucose tolerance test remained non-suppressible. Tumour sizes were not affected. Two women became pregnant and were delivered of healthy babies. Side-effects typical of bromocriptine occurred frequently on the days of injection and diminished in most patients after 2 months of therapy despite increasing dosage. Compared with previous oral bromocriptine therapy, 9 of 10 patients preferred the depot preparation, whereas the reduction of growth hormone levels was similar during both treatments. In conclusion, depot-bromocriptine should be considered for acromegalic patients intolerant to oral bromocriptine.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 72 (1994), S. 451-456 
    ISSN: 1432-1440
    Keywords: Bromocriptine ; Prolactinoma ; Roxindol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We studied the effects of the new non-ergot D2-dopamine agonist roxindol for the treatment of human prolactinomas. Roxindol is a non-ergot drug with additional 5-hydroxytryptamine type 1 A agonist and serotonin reuptake inhibitory activity. Ten patients with prolactin-secreting pituitary adenomas received roxindol three times daily at a dosage of 7.5–30 mg/day for at least 4 weeks according to a prospective protocol. All patients but one had received oral bromocriptine previously without normalization of prolactin levels. Serum prolactin profiles were analyzed once a week during the first month of therapy and at 4-week intervals thereafter. Mean baseline serum prolactin was suppressed from 23000±13 600 mU/1 (range 1500–141000 mU/1; 20 mU/l=1 μg/1) by 37 ± 11 % after 1 week, by 49±9% after 4 weeks, and by 65±11% (n = 8) after 24 weeks of treatment. Serum prolactin was normalized in two patients. A tumor volume reduction of 20–25% was obtained in two subjects. Compared with previous treatment with oral bromocriptine the decrease in serum prolactin was comparable. In contrast, tolerance of roxindol was superior in five of seven patients with major side effects with bromocriptine, including three subjects who had discontinued bromocriptine because of adverse reactions. Four subjects spontaneously reported improvement of psychological and physical performance. One patient had a transient increase of serum transaminases. Thus, for the first time we could show a suppressive effect of roxindol on prolactin secretion in human prolactinomas. Due to its good tolerance roxindol may provide a useful alternative to bromocriptine.
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