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Biomedical subjects

D B Ramsden

Publications and source records attributed to D B Ramsden.

At least 91 records · Page 5Linked to original sources
PubMed1985

Conflict between classifications based on free thyroxine and thyroid stimulating hormone concentrations in thyroxine-treated patients.

The use of free thyroxine assay as the basis for monitoring patients on thyroxine replacement therapy was assessed. Patients with normal free thyroxine levels were divided into sub-groups on the basis of serum TSH levels. Of these, patients with normal TSH levels had higher serum free thyroxine and free 3,5,3'-triiodothyronine concentrations than patients with elevated TSH levels. No significant differences were seen in the level of duration of replacement therapy. Patients were almost equally divided between the high and normal TSH sub-groups. It was concluded that free thyroxine assay had little role to play in the monitoring of these patients.

Humans↗
PubMed1985

Down-regulation of nuclear T3 receptors by thyroid hormones in the rat anterior pituitary.

The concentration of T3 nuclear receptors may be modulated by thyroid hormones. We have examined the effect of thyroid hormone excess and deficiency in the rat on the in vitro binding of T3 to anterior pituitary nuclear receptors. Nuclei prepared from hypothyroid, hyperthyroid and control rats by homogenisation and centrifugation were incubated with [125I]T3 and unlabelled T3 at increasing concentrations. After incubation for 60 min at 37 degrees C, nuclei were separated by filtration and bound radioactivity counted. Scatchard analysis of binding data revealed no significant difference in binding affinity or capacity for T3 between nuclei from hypothyroid and control rats. Results from hyperthyroid and control animals revealed no change in affinity, but a marked reduction in binding capacity was observed, suggesting depletion of receptor number. This finding of down-regulation may represent a protective mechanism against the effects of high circulating thyroid hormone levels on the tissues.

Animals↗
PubMed1985

Amiodarone and thyroid hormone action.

In clinically euthyroid subjects on long-term amiodarone therapy free thyroxine (T4) concentrations were increased and free triiodothyronine (T3) levels reduced. There was also a marked increase in reverse T3 in the treated group. These changes are consistent with inhibition of peripheral deiodination of T4 and reverse T3. Despite the rise in T4 serum thyrotrophin (TSH) levels were increased, suggesting an effect of amiodarone on the anterior pituitary. To investigate the interaction of amiodarone with the cellular actions of thyroid hormones we examined the influence of the drug in vitro on the binding of T3 to isolated nuclei prepared from rat anterior pituitary tissue. Amiodarone inhibited the nuclear binding of T3 in a dose dependent fashion. Addition of amiodarone in vitro also stimulated TSH release from cultured rat anterior pituitary cells, consistent with a T3 antagonistic effect. These studies provide evidence for a direct influence of amiodarone on the thyrotroph, mediated via nuclear T3 receptor binding.

Adult↗
PubMed1985

Abnormalities of thyroid function tests in hospital inpatients.

Results of thyroid function tests were analysed in 199 clinically euthyroid inpatients with normal serum thyroid stimulating hormone values. Serum total triiodothyronine was less than 1.25 nmol/l in 61.8% of samples, free triiodothyronine less than 3.9 pmol/l in 57.8%, total thyroxine less than 63 nmol/l in 21.1% and free thyroxine less than 9.5 pmol/l in 17.6%. In contrast, thyroxine binding globulin ratio was below normal (less than 5) in only 5 samples. A significant positive correlation (P less than 0.001) of serum free thyroxine with total thyroxine, thyroxine/thyroxine binding globulin ratio and free triiodothyronine was present as well as a significant negative correlation (P less than 0.001) with serum thyroid stimulating hormone. There was no correlation of free thyroxine measurements with serum albumin or non-esterified fatty acid concentrations. Although serum free thyroxine is low in a number of patients with non-thyroidal illnesses, this does not appear to be due to a rise in non-esterified fatty acids or a fall in albumin as has been proposed. Serum thyroid stimulating hormone measurements are essential to confirm the diagnosis of hypothyroidism in such subjects.

Humans↗
PubMed1985

The influence of age and sex on tests of thyroid function.

Serum concentrations of total thyroid hormones, thyroid hormone binding proteins, free thyroid hormones and thyroid stimulating hormone (TSH) were measured in a large group of healthy normal subjects (n = 218) to determine the influence of age and sex on tests of thyroid function. No effect of age on measurements of total thyroxine (T4), total triiodothyronine (T3) or reverse T3 was evident. Concentrations of free T4, free T3 and TSH were similarly unaffected, suggesting that increasing age alone does not significantly influence thyroid hormone measurements. There was, however, a rise in thyroxine-binding globulin (TBG) concentration with increasing age and a fall in thyroxine-binding prealbumin (TBPA). An influence of sex on tests of thyroid function was clearly evident. Levels of total T4, total T3, free T4 and the T4: TBG ratio were lower in women between 16 and 49 years than in men, despite an increase in TBG. Lower levels of free T3 were confined to the group of women aged 16-29 years. TSH values were unaffected by sex. These results suggest that sex hormone status in the pre-menopausal female subject may result in an increase in TBG concentration, and in addition may have an opposing effect on circulating thyroid hormone concentrations.

Adolescent↗
PubMed1985

The effect of propranolol on circulating thyroid hormone measurements in thyrotoxic and euthyroid subjects.

Circulating concentrations of total and free thyroid hormones and thyroid hormone binding proteins were measured in thyrotoxic and euthyroid subjects treated with propranolol. In the thyrotoxic group, total triiodothyronine (T3) concentration fell after propranolol therapy, suggesting an effect of the drug on the peripheral conversion of thyroxine (T4) to T3. In euthyroid subjects, a rise in circulating concentrations of free T4 and reverse T3 (rT3) was observed, while only a small decrease in free T3 was evident. Thyroxine binding globulin (TBG) concentration fell during propranolol treatment while thyroxine binding prealbumin (TBPA) concentration rose. The changes observed in the euthyroid state are consistent with inhibition of peripheral deiodination of T4 and rT3; an additional effect of propranolol on binding protein metabolism was evident.

Humans↗
PubMed1985

Phenytoin and thyroid hormone action.

Circulating free thyroid hormone concentrations are reduced in subjects taking long-term phenytoin, a finding at variance with their euthyroid clinical state and normal serum TSH concentration. It is suggested, therefore, that phenytoin may modify the cellular effects of thyroid hormones. In order to examine the influence of phenytoin on thyroid hormone action in the pituitary gland we studied its effect on the binding of tri-iodothyronine (T3) to isolated nuclei prepared from rat anterior pituitary tissue. Phenytoin inhibited the nuclear binding of T3 in a dose-dependent fashion. Phenytoin also partially inhibited thyrotrophin-releasing hormone-stimulated TSH release from cultured rat anterior pituitary cells. These studies provide evidence for a direct effect of phenytoin on the thyrotroph mediated via nuclear T3 receptor binding.

Animals↗
PubMed1984

Mass spectral properties of volatile derivatives of thyronine (T0) and use of these in the study of thyronine excretion in eu-, hyper- and hypothyroidism.

The mass spectral properties of four classes of derivatives of thyronine are discussed ( oxazolidinone , O-methyl oxazolidinone , O-acetyl oxazolidinone and N,O- diheptafluorobutyryl methyl ester). An assay for thyronine in human urine is described based on the N,O- diheptafluorobutyryl methyl ester. Results of T0 excretion in euthyroid humans were compared with those obtained previously using an assay based on the O-acetyl oxazolidinone derivative. Patients with frank hyperthyroidism had significantly higher T0 excretion than euthyroid subjects (2 alpha less than 0.002) and hypothyroid patients lower T0 excretions than euthyroid subjects (2 alpha less than 0.002). Some overlap between the two pathological ranges and the normal euthyroid range was evident.

Humans↗
PubMed1984

Development of a gas chromatographic selected ion monitoring assay for thyroxine (T4) in human serum.

The components of a gas chromatographic mass spectrometric-selected ion monitoring (SIM) assay for thyroxine (T4) in human serum are described. The internal standard for the assay was synthesized from deuterium-labelled 3,5-diiodotyrosine and 3,5-diiodo-4-hydroxyphenylpyruvic acid. A novel method was developed for isolating the products of the coupling reaction. The results obtained by gas chromatography mass spectrometry SIM were compared with those of radioimmunoassay. The gas chromatographic mass spectrometric SIM assay would form the basis of a reference assay for T4.

Chromatography, Gas↗
PubMed1984

Measurement of free thyroid hormones in patients on long-term phenytoin therapy.

Total thyroxine and triiodothyronine levels are often reduced in long-term phenytoin therapy, a finding at variance with the euthyroid clinical state of these subjects. We have measured free (biologically active) thyroid hormone levels in 31 patients on phenytoin therapy and have found a significant reduction in measurements of both free thyroxine and free triiodothyronine. In contrast, addition of phenytoin to normal serum in vitro resulted in an increase in free thyroxine and free triiodothyronine concentrations. The findings in vitro are consistent with displacement of thyroid hormones from thyroxine binding globulin while the reduced free hormone levels in vivo confirm that the effects of phenytoin are not confined to binding inhibition and suggest that phenytoin has induced a change in the cellular metabolism of thyroid hormones.

Humans↗
PubMed1984

Thyroid status in patients after acute myocardial infarction.

Subjects followed serially after acute myocardial infarction demonstrated a rapid and sustained fall in serum total tri-iodothyronine (T3) concentration and a rise in reverse tri-iodothyronine (rT3) concentration. There was a transient fall in total thyroxine (T4) concentration. Thyroxine binding globulin (TBG) levels were unchanged after acute myocardial infarction but prolonged falls were observed in thyroxine binding prealbumin (TBPA) and albumin concentrations. In contrast to the fall in total T4, both measured and calculated free T4 concentrations were unchanged but measured and calculated free T3 concentrations fell as did total T3. Despite the observed fall in T3, basal thyrotrophin (TSH) concentrations did not rise. The reduction in circulating T3 levels after acute myocardial infarction suggests that a hypothyroid state exists. Until tissue thyroid status can be assessed directly, however, this conclusion must remain in doubt.

Acute Disease↗
PubMed1984

Measurement of free thyroxine and free triiodothyronine in thyrotoxicosis and hypothyroidism.

Free T4 and free T3 concentrations in thyrotoxic and hypothyroid patients at presentation differentiated those with thyroid disease from euthyroid control subjects and were closely correlated with T4/TBG ratio. A further group of thyrotoxic patients was followed serially during treatment with carbimazole. Measurements of free T4 and free T3 against closely reflected thyroid status with changes in the hormone measurements being paralleled by changes in T4/TBG ratio.

Carbimazole↗
PubMed1984

Measurement of free thyroxine and free triiodothyronine in asymptomatic subjects with high concentrations of serum TSH and a history of radioiodine therapy.

Total and free thyroid hormones were measured in a group of asymptomatic subjects with high circulating TSH concentrations and a previous history of radioiodine therapy. Subjects in the high TSH group all fell within the normal range for measurements of total T4, total T3 and T4/TBG ratio. Concentrations of free T4 or free T3 were below the normal range in more than half (9 out of 17) of the high TSH group suggesting that these measurements are more sensitive indices of thyroid failure than measurement of total hormones or T4/TBG ratio.

Humans↗
PubMed1984

Effect of repeated stimulation by thyrotropin-releasing hormone (TRH) on thyrotropin and prolactin secretion in perfused euthyroid and hypothyroid rat pituitary fragments.

The previously reported refractoriness of pituitary response to thyrotropin-releasing hormone (TRH) stimuli was investigated here in an in vitro perfusion system using pituitary tissue from euthyroid and hypothyroid rats. Thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to TRH (28 pmol) were significantly greater in hypothyroid tissue compared with euthyroid. Hypothyroid tissue showed a reduction in response to two consecutive stimuli in both TSH and PRL, however the TSH decline in response was more marked than PRL. Euthyroid tissue showed no significant decline in response to TRH. An increase in the dose of TRH (112 pmol), administered to euthyroid tissue, resulted in increased TSH and PRL response, but no decline in response to sequential stimuli was observed. Three consecutive stimuli by TRH (28 pmol) of hypothyroid tissue resulted in a consistent decline in TSH response. The decline in PRL response only reached statistical significance by the third stimulation. Euthyroid and hypothyroid pituitary tissue was subjected to sequential depolarising stimulation with KCl (50 mumol). Euthyroid tissue showed no decline in response in either TSH or PRL. In hypothyroid tissue only, the decline in TSH response reached statistical significance. This decline in TSH response was significantly smaller than the decline in response observed in hypothyroid tissue stimulated with TRH. Refractoriness of hypothyroid pituitary tissue to repeated TRH stimuli is reported here. Our data suggest that the decline in hormonal response cannot be explained solely on the basis of tissue depletion.

Animals↗
PubMed1984

The effect of neurotensin on pituitary secretion of thyrotrophin and prolactin in vitro.

The effects of neurotensin on thyrotrophin (TSH) and prolactin (Prl) release were studied in two in vitro systems - anterior pituitary cells in culture and perifused anterior pituitary fragments. Neurotensin significantly reduced basal secretion of both TSH and Prl (P less than 0.001) from cultured pituitary cells, and abolished thyrotrophin releasing hormone (TRH)-stimulated TSH thyrotrophin releasing hormone (TRH)-stimulated TSH TSH and Prl release (P less than 0.02) from perifused pituitary fragments. These data indicate that neurotensin has a direct inhibitory effect on TSH and Prl secretion by the anterior pituitary.

Animals↗
PubMed1983

Neurotensin regulation of TSH secretion in the rat.

Tri-iodothyronine stimulates neurotensin secretion from rat hypothalami in vitro. Propylthiouracil treatment of rats is associated with a decrease in anterior pituitary neurotensin content, an increase in hypothalamic content and an impaired release of peptide from hypothalami in vitro. In addition neurotensin has a direct inhibitory effect on TRH-stimulated TSH release from anterior pituitary in vitro. These observations suggest a physiological role for neurotensin in the control of TSH secretion in the rat.

Animals↗