Radioimmunoassay for Serum Thyroxine-Binding Globulin: Results in Normal Subjects and in Patients with Hepatocellular Carcinoma

Mc, Gershengorn; Larsen, Peder Olesen; Robbins, Jacob

doi:10.1210/jcem-42-5-907

Cited by 56 publications

(15 citation statements)

References 10 publications

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“…Die radioimmunchemische zu einer Unsicherheit gegenüber der TBG-BestimBestimmung von TBG hat in den letzten Jahren im-mung geführt. Wir haben daher TBG erneut hochgemer mehr zu einer wertvollen Bereicherung in der reinigt und chemisch charakterisiert, worüber an anSchilddrüsendiagnostik selbst beigetragen (3,(8)(9)(10)(11)(12)(13)(14)(15)(16). derer Stelle berichtet wird.…”

Section: Einführungunclassified

“…Aus früheren präparativen Untersuchungen war schon bekannt, daß ein unterschiedliches Molekulargewicht von etwa 60000 + 3000 angegeben wurde (l, 4, 20, 21, 22 Theoretische Berechnungen lassen die Konzentration von zirkulierendem TBG im Serum bei 10 mg/1 erwarten (l, 21, 23). Die von anderen Autoren (9,10,31) radioimmunchemisch ermittelten Konzentrationen bei gesunden Probanden lagen nahe an diesem Erwartungswert, der auch mit unserer enzymimmunologischen Methode annäherungsweise gemessen wird. Von mehreren Autoren wurden aber teilweise wesentlich höhere Konzentrationen angegeben (6,3,11,32).…”

Section: Charakterisierung Des Tbgunclassified

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Methodische und klinische Evaluation einer neuen enzymimmunologischen Methode zur Bestimmung des Thyroxin bindenden Globulins (TBG) und des T4/TBG-Quotienten: Eine multizentrische Studie

Kessler¹,

Rudorff²,

Oellerich³

et al. 1985

Clinical Chemistry and Laboratory Medicine

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Melhodological and clinical evaluation ofa new enzyme immunological methodfor the determinaüon ofthyroxine binding globulin (TBG) and the T^TBG ratioSummary: A heterogeneous enzyme immunoassay for the determination of thyroxine binding globulin (TBG) was developed and assessed in clinical trials in 12 laboratories. The assay is based on the competition principle and employs plastic tubes coated with goat anti-TBG. CV's between 1.4-8.9% for intra-assay precision and 2.9 -8.6% for inter-assay precision were found over the concentration ränge of 4-40 mg/1 TBG. In comparative studies using highly purified TBG äs Standard, values with Enzymun-Test® TBG were found to be on average 30% lower than those obtained by various TBG-RIAs. A broad-base study, to determine reference values, was carried out on a group of control persons 18 to 50 years old without previous history of thyroid disease. This study revealed a median of 14.33 mg/1 TBG, with 95% of all values between 9.6 and 18.5 mg/1 TBG. The median in wpmen of 14.5 mg/1 TBG was significantly higher than in men (l 3.4 mg/1 TBG). TBG values in hyperthyroid patients were within the reference ränge while those in hypothyroid individuals were elevated. Highly elevated TBG values were seen in women receiving oestrogen (median: 22.2 mg/1 TBG) and in pregnant women (median: 28.5 mg/1 TBG). The T 4 /TBG ratios made it possible to distinguish between euthyroid, hyperthyroid and hypothyroic subjects (median: 4.9, 11.3 and 1.0, respectively). These ratios were significantly lower in pregnant women (median: 3.1) than in the control persons. EinführungThyroxin bindende Globulin (T 4 /TBG)-Verhältnis kann die Fraktion des freien T 4 errechnet werden Das Thyroxin bindende Globulin (TBG) ist das (14). Wir sehen in der getrennten Bestimmung von Transportprotein für lodthyronine mit der höchsten zwei kenngrößenabhängigen Größen einen großen Affinität (l). Seine Aminosäurenzusammensetzung ist klinischen Vorteil gegenüber der direkten Bestimbekannt, obwohl sie in unterschiedlichen Arbeiten mung von freiem T 4 . Die Problematik der TBGverschieden angegeben wird (2, 3). Seine Aminosäure-Bestimmung liegt in ihrer bisher mangelnden Startsequenz ist nur teilweise aufgeklärt, da genügende dardisierung. Aus Mangel an genügend hochreinem, Mengen an hochreinem TBG für solche Analysen chemisch gut charakterisierten TBG liegt keine ehl·-bislang nicht vorlagen (4). Trotz dieses Mangels ist heitliche Referenzpräparation und damit kein gültiger die physiko-chemische Funktion von TBG hinrei-Referenzbereich vor. Dies hat vor allem in der Klinik chend untersucht (1-7). Die radioimmunchemische zu einer Unsicherheit gegenüber der TBG-BestimBestimmung von TBG hat in den letzten Jahren im-mung geführt. Wir haben daher TBG erneut hochgemer mehr zu einer wertvollen Bereicherung in der reinigt und chemisch charakterisiert, worüber an anSchilddrüsendiagnostik selbst beigetragen (3,(8)(9)(10)(11)(12)(13)(14)(15)(16). derer Stelle berichtet wird. Mit dem so gewonnenen Dies gilt vor allem auch für extrathyreoidale ...

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Section: Einführungunclassified

Section: Charakterisierung Des Tbgunclassified

Methodische und klinische Evaluation einer neuen enzymimmunologischen Methode zur Bestimmung des Thyroxin bindenden Globulins (TBG) und des T4/TBG-Quotienten: Eine multizentrische Studie

Kessler¹,

Rudorff²,

Oellerich³

et al. 1985

Clinical Chemistry and Laboratory Medicine

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“…Despite this, clinical evidence of hypothyroidism is uncommon and direct measurement of free T4 (fT4) or the free thyroxine index has usually given normal values (Green et al, 1970;Liewendahl et al, 1983). In contrast, hyperthyroxinaemia has been described in some patients with hepatocellular carcinoma (HCC), a frequent complication of long-standing cirrhosis (Gershengorn et al, 1976;Kalk et al, 1982;Nelson, 1979). The hyperthyroxinaemia has been attributed to elevated levels of thyroxine binding globulin (TBG) but whether abnormalities of other thyroid binding proteins such as albumin and prealbumin are also involved has not been determined.…”

mentioning

confidence: 99%

Hyperthyroxinaemia in hepatocellular carcinoma: Relation to thyroid binding globulin in the clinical and preclinical stages of the disease

Alexopoulos

Hutchinson²,

Bari³

et al. 1988

Br J Cancer

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Summary Serum thyroxine was significantly higher in 59 patients with hepatocellular carcinoma than in normal subjects, patients with uncomplicated cirrhosis (48), or other primary tumours with or without hepatic metastases (50). Elevated thyroxine levels appeared attributable to high levels of thyroxine binding globulin which showed a positive linear correlation with serum thyroxine in all groups studied. Despite this hyperthyroxinaemia all patients appeared clinically euthyroid and, consistent with this, T3 was elevated in only one patient and the free thyroxine index was normal in all. Amongst a group of 25 cirrhotic patients who were followed-up for between 12 and 72 months, there was a striking dissociation between the TBG values of those destined to develop HCC and those who did not. In the former group TBG rose steadily with time whereas in the latter group levels remained stable, or, more often, fell. The rises in TBG occurred prior to any clinical signs of tumour development and may be one of the earliest serological changes to occur during carcinogenesis in the cirrhotic liver.Changes in the serum levels of thyroid hormones and their binding proteins in patients with cirrhosis are welldocumented (Chopra et al., 1974;Hepner & Chopra, 1979; Lumholtz et al., 1978;Nomura et al., 1975). Most studies have shown a normal thyroxine (T4) level with impaired conversion to triiodothyronine (T3) resulting in low levels of T3 and high levels of reverse T3 (rT3). Despite this, clinical evidence of hypothyroidism is uncommon and direct measurement of free T4 (fT4) or the free thyroxine index has usually given normal values (Green et al., 1970;Liewendahl et al., 1983). In contrast, hyperthyroxinaemia has been described in some patients with hepatocellular carcinoma (HCC), a frequent complication of long-standing cirrhosis (Gershengorn et al., 1976;Kalk et al., 1982;Nelson, 1979). The hyperthyroxinaemia has been attributed to elevated levels of thyroxine binding globulin (TBG) but whether abnormalities of other thyroid binding proteins such as albumin and prealbumin are also involved has not been determined. There are also no data on how levels of TBG change before diagnosis of HCC or whether such changes are specific for HCC or occur generally in malignant disease.In the present study we have measured the serum thyroid hormones together with their binding proteins in a large series of patients with HCC and various control groups including uncomplicated cirrhosis and other primary tumours with or without hepatic metastases. In healthy volunteers recruited from the ho6pital staff. None of the subjects studied was receiving drugs known to interfere with thyroid function. In all patients with HCC the serum samples studied were those collected at the time of diagnosis and prior to any treatment.The stored serial sera (which had been frozen once and not previously thawed before the assay) came from patients included in a prospective study of the development of HCC in cirrhosis (Zaman et al., 1985). These comprised 25 pati...

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“…Previously Pederson (1974) had reported that hepatocellular carcinoma was occasionally associated with an increase in serum TBG. However, Gershengorn et al (1976) demonstrated that TBG was far from constant and was not correlated with the The relation between serum TBG and serum CEA was examined in many cancer patients, but no correlation was found (Fig. 6).…”

Section: Discussionmentioning

confidence: 99%

Clinical study on increased serum thyroxine-binding globulin in cancerous state.

Kajita¹,

Ishida²,

Hachiya

et al. 1981

Endocrinol Japon

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Radioimmunoassay for Serum Thyroxine-Binding Globulin: Results in Normal Subjects and in Patients with Hepatocellular Carcinoma

Cited by 56 publications

References 10 publications

Methodische und klinische Evaluation einer neuen enzymimmunologischen Methode zur Bestimmung des Thyroxin bindenden Globulins (TBG) und des T4/TBG-Quotienten: Eine multizentrische Studie

Methodische und klinische Evaluation einer neuen enzymimmunologischen Methode zur Bestimmung des Thyroxin bindenden Globulins (TBG) und des T4/TBG-Quotienten: Eine multizentrische Studie

Hyperthyroxinaemia in hepatocellular carcinoma: Relation to thyroid binding globulin in the clinical and preclinical stages of the disease

Clinical study on increased serum thyroxine-binding globulin in cancerous state.

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