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Biomedical subjects

A D Toft

Publications and source records attributed to A D Toft.

At least 19 recordsLinked to original sources
PubMed1991

The clinical utility of a non-isotopic two-step assay (DELFIA) and an analogue radioimmunoassay (SimulTRAC) for free thyroxine compared.

The analytical and diagnostic performance of a new non-isotopic, two-step immunoassay (DELFIA) for the measurement of free thyroxine (free T4) in plasma or serum has been compared with an established second generation analogue radioimmunoassay (SimulTRAC). Both methods had a good diagnostic specificity in pregnancy, thyroid clinic patients, and patients taking anticonvulsant drugs. In patients presenting to a general medical ward the diagnostic specificity of both methods was poor. Two samples appeared to contain substances which produced assay interference by DELFIA but not by SimulTRAC assays. When free T4 was measured by equilibrium dialysis a clear association between sample dilution and free T4 concentration was demonstrated in sick euthyroid patients. In contrast, using samples obtained from patients with known thyroid disease, free T4 was little influenced by sample dilution. The effects of sample dilution on free T4 measured by DELFIA were similar to those found using equilibrium dialysis. It would appear that free T4 measurements have a relatively poor diagnostic specificity in non-thyroidal illness irrespective of the method used.

Anticonvulsants↗
PubMed1991

Inter-relationships between selenium and thyroid hormone metabolism in the rat and man.

Labelling of rat kidney microsomes in vitro with [125I]-bromoacetyl T4 produced two bands on SDS/PAGE with Mr of 55 kDa and 27.5 kDa representing protein disulphide isomerase and type I iodothyronine deiodinase (ID-I) respectively. The amount of the 55 kDa band was unchanged by selenium (Se) deficiency but the 27.5 kDa protein was markedly decreased in kidney microsomal fraction obtained from Se-deficient rats. Concurrent Se and iodine deficiency produced a significant increase in thyroid weight, plasma thyrotrophin (TSH) and a decrease in thyroidal iodine when compared with either single Se or iodine deficiency. These results suggest that ID-I is a selenoprotein and that Se deficiency can exacerbate the hypothyroidism observed in iodine deficiency. In man, blood glutathione peroxidase and blood Se levels were decreased in hyperthyroidism due to Graves' disease whilst normal levels of these analytes were found in patients treated for Graves' disease. These results suggest that thyroid status can affect Se balance rather than Se deficiency predisposes to Graves' disease.

Animals↗
PubMed1990

Non-isotopic, two-step free thyroxine immunoassay: a better measure of free thyroxine than analogue radioimmunoassay.

Plasma or serum free thyroxine (T4) was measured by a novel non-isotopic, two-step immunoassay in 373 consecutive patients attending a thyroid clinic, in whom thyroid status was categorized according to clinical findings, supported by routine thyroid function tests. The 95% confidence limit of free T4 in the euthyroid patients (n = 112) was 7-20 pmol/L. Free T4 concentrations within the reference range were found in six of 40 patients with primary hypothyroidism and nine of 182 patients with overt thyrotoxicosis, six of whom had T3 toxicosis. Serum or plasma free T4 measured by the two-step method showed improved diagnostic specificity over an analogue RIA in selected groups of euthyroid patients in whom abnormal binding of analogue T4 can affect the validity of the result. Free T4 results found by analogue RIA and the two-step method in 58 patients who were receiving thyroxine replacement therapy were similar. The between-assay precision of the two-step method was poor ranging from a coefficient of variation of 9.7% to 19.3% over a free T4 concentration range of 5.0 to 46.0 pmol/L. We conclude that the two-step methodology offers diagnostic advantages for a laboratory which receives specimens from such patients for exclusion of thyroid disease but that improved assay precision is required before it could be used in a routine situation.

Autoantibodies↗
PubMed1990

Secretor status and infection in patients with Graves' disease.

We have demonstrated that the inability to secrete the water soluble glycoprotein form of the ABO blood group antigens into saliva is significantly more common in patients with Graves' disease than control subjects (40% vs 27%: P less than 0.025) but not among those with Hashimoto's thyroiditis or spontaneous primary atrophic hypothyroidism. Non-secretion is associated with increased susceptibility to infection and to asymptomatic carriage of some microorganisms. Although Yersinia enterocolitica has been found to express antigen cross reactive with the TSH receptor, we did not find an increased prevalence of Yersinia species in the faeces of 107 patients with Graves' disease. The isolation rate (less than 1%) was similar to that observed in the local population with diarrhoeal illness. Salivary IgA levels determined by whole cell ELISA with Y. enterocolitica 03 were not elevated in the majority of specimens examined. The results suggest that in contrast to reports from Scandinavia, there is no strong evidence that yersiniae play a role in the pathogenesis of Graves' disease among patients in South east Scotland. Non-secretors are significantly over represented among patients with several other autoimmune diseases; however, with the exception of antitubulin antibodies, non-secretors with Graves' disease did not have more antibodies to other human antigens than secretor patients.

ABO Blood-Group System↗
PubMed1989

Different hepatic responses to thyroxine replacement in spontaneous and 131I-induced primary hypothyroidism.

The serum levels of a range of analytes known to change with thyroid status were measured in two groups of patients with primary hypothyroidism commencing T4 replacement therapy. One group (group 1; n = 9) had spontaneous hypothyroidism whilst in the second (group 2; n = 10), hypothyroidism had resulted from radioiodine therapy. The replacement dose was increased in 50 micrograms increments each month to 200 micrograms/day; this produced similar serum concentrations of thyroid hormones and TSH in the two groups at each dose. Dose-dependent increases in glutathione S-transferase (GST) were seen in both groups but changes in alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) activities occurred only in group 1 patients. Group 1 patients had significantly higher levels of GST than group 2 at the 150 micrograms (P less than 0.01) and the 200 micrograms (P less than 0.005) doses of T4, and they had higher activities of ALT (P less than 0.01) and GGT (P less than 0.02) at the 200 micrograms dose. Seven patients in group 1 had abnormalities in GST and four had high levels of ALT, whereas three patients from group 2 had high GST concentrations and all had ALT activities within reference limits. The concentrations of the other analytes measured in serum showed the same response to T4 in the two groups, particularly the concentrations of certain transport proteins whose serum concentrations depend on hepatic protein synthesis. These data suggest that patients with spontaneous primary hypothyroidism are more susceptible to hepatocellular damage than patients who have radioiodine-induced primary hypothyroidism when given oral doses of thyroxine greater than 150 micrograms/day.

Adult↗
PubMed1989

Resistant hyperthyroidism induced by sodium iopodate used as treatment for Graves' disease.

Sodium iopodate has recently been advocated for long-term control of hyperthyroidism in Graves' disease. Its advantages over conventional therapy are a rapid fall in thyroid hormones and control of symptoms with a simple dosage regime. We report a case in which severe resistant hyperthyroidism developed during treatment of Graves' disease with sodium iopodate. Sodium iopodate may not be suitable for long-term use in all patients with Graves' disease.

Adult↗
PubMed1989

Alkaline phosphatase isoenzymes in plasma in hyperthyroidism.

Alkaline phosphatase (ALP; EC 3.1.3.1) isoenzymes were measured in the plasma of 63 untreated hyperthyroid patients (the hyperthyroid group), 58 treated hyperthyroid patients, and 100 blood donors. Total, liver, and bone ALP activities were significantly higher in the hyperthyroid group than in the treated hyperthyroid group or the blood donors. Bone ALP was more frequently and more markedly abnormal than liver ALP. Intestinal ALP did not differ significantly between the groups. The hyperthyroid patient group had significantly higher plasma calcium concentrations and lower serum parathyrin concentrations than those of the treated hyperthyroid group.

Adult↗
PubMed1988

Use of sensitive immunoradiometric assay for thyrotropin in clinical practice.

Although measurement of thyrotropin (thyroid-stimulating hormone; TSH) by radioimmunoassay was a major advance in the laboratory diagnosis of thyroid failure--replacing the time-consuming TSH stimulation test--it was not sufficiently sensitive to discriminate reliably between euthyroid and hyperthyroid patients. Measurement of the TSH response to thyrotropin releasing hormone (TRH) served this purpose, however. The recent development of TSH assays that are severalfold more sensitive and more specific than conventional radioimmunoassays has allowed distinction of euthyroid from hyperthyroid patients and eliminated the need for the TRH test. Although undetectable levels of TSH, compatible with hyperthyroidism, are occasionally noted in euthyroid patients with severe nonthyroidal illness and during the first trimester of pregnancy, false-positive results are less often recorded for TSH than for free or total thyroid hormone measurements. Measurement of TSH by sensitive immunoradiometric assay is currently the most useful first-line test of thyroid function in patients with suspected thyroid disease and, in addition, has a valuable role in monitoring the dose of thyroxine replacement therapy.

Antibodies, Monoclonal↗
PubMed1988

The replacement therapy problem in hypothyroidism.

There is increasing evidence from studies of heart rate, liver enzyme activity, bone density and urinary sodium excretion that standard replacement therapy doses of thyroxine which suppress TSH secretion are associated with changes in target organ function similar to, but less marked than, those recorded in overt hyperthyroidism. There is also evidence that in subclinical hypothyroidism it is not only the pituitary thyrotroph which recognizes a minor reduction in serum thyroid hormone levels within the normal range. Although there is no proof that slight 'overtreatment' with thyroxine or non-treatment of subclinical hypothyroidism is detrimental to the patient in the long term, the appropriate studies have not been performed. It would seem good clinical practice, however, to treat all grades of thyroid failure and to ensure, if possible, that the dose of thyroxine is adjusted to maintain a normal and detectable TSH level when measured by a sensitive assay system. It must be conceded, however, that with the vagaries of human nature there is always likely to be greater morbidity from patients with hypothyroidism failing to take their medication regularly, than from failure by the medical attendant to make minor adjustments to the dose of thyroxine.

Humans↗
PubMed1988

Restoration of normal thyrotrophin secretion reduces the abnormally high serum glutathione S-transferase levels found in patients receiving thyroxine replacement therapy.

The peripheral tissue thyroid status of 12 patients receiving thyroxine replacement therapy was investigated both when pituitary secretion of TSH was suppressed and later, when on a lower dose of thyroxine that restored thyrotroph responsiveness. Heart rate and various analytes in serum known to be sensitive to thyroid status were measured in addition to TSH by immunoradiometric assay. Initially, the serum T4 concentration was raised in seven patients and free T4 raised in nine; all patients had normal T3 concentrations. Later, on the lower dose of thyroxine, most patients had concentrations of thyroid hormones within reference limits. Concentrations of the liver-specific form of glutathione S-transferase (GST) in serum decreased (P less than 0.01) after the reduction in thyroxine dose; abnormally high GST levels, found in eight patients when TSH was suppressed, returned to normal in six of these patients when normal basal and TRH-stimulated TSH concentrations had been restored. The response of the pituitary to excess thyroxine may be more representative of other tissues (e.g. the liver) than previously thought.

Adult↗
PubMed1987

Laboratory and diagnostic performance of a coated well immunoradiometric assay for serum thyrotrophin.

A new, coated well immunoradiometric assay (IRMA) for thyrotrophin (TSH) in serum has been evaluated with a view to its use as a first-line test of thyroid function. The Amerwell TSH IRMA is simple, rapid to perform (2.5 h) and the assay sensitivity was 0.07 mU/L with a working range (intra-assay CV less than 10%) of 0.3-100 mU/L. The mean inter-assay CV was 6.6% for TSH concentrations of 0.30-30.7 mU/L. The method compared favourably with an in-house TSH radioimmunoassay and an alternative commercial IRMA. In consecutive referrals to a thyroid clinic all patients with overt hyperthyroidism (n = 103) had undetectable TSH concentrations and in those with subclinical hyperthyroidism (n = 14). TSH was undetectable in 10 and below the reference range in four. The 95% confidence interval for 63 euthyroid serum samples was 0.36-4.3 mU/L. All hypothyroid patients (n = 20) had increased TSH concentrations. TSH concentrations in pregnancy did not differ significantly from euthyroid TSH values. From 1916 routine tests, 13 undetectable TSH values were found in which thyroid hormone levels were normal and the patients had no known thyroid disorder. The assay appears suitable as a first-line test of thyroid function, but further assessment in a routine laboratory setting is required.

Humans↗