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Biomedical subjects

A D Toft

Publications and source records attributed to A D Toft.

At least 73 records · Page 4Linked to original sources
PubMed1986

An improved approach to thyroid function testing in patients with non-thyroidal illness.

We have compared the results of serum thyrotrophin (TSH) measurements using a sensitive immunoradiometric assay (IRMA) with those of conventional thyroid function tests in 299 hospital inpatients with a range of non-thyroidal illnesses. Levels of total thyroxine (T4), free T4, total tri-iodothyronine (T3) and free T3 in the hypothyroid range were recorded in 8%, 15%, 19% and 49% of patients, respectively, whereas TSH (IRMA) was abnormally low in 1%. Furthermore, basal TSH (IRMA) accurately predicted the result of the thyrotrophin-releasing hormone test in 72 of the 74 patients in whom this test was performed and, unlike thyroid hormone measurement, identified patients with subclinical thyroid disease. It would appear that a single basal TSH (IRMA) measurement is the most appropriate screening test for thyroid dysfunction in patients with concomitant acute or chronic illness.

Adolescent↗
PubMed1986

Problems of anticoagulation with warfarin in hyperthyroidism.

From clinical observation it would appear that hyperthyroid patients are particularly sensitive to the anticoagulant effects of warfarin. A study was made of clotting factors prothrombin (II), VII, procoagulant VIII (VIIIC), IX and X and of prothrombin ratio (PTR) and partial thromboplastin time with kaolin (PTT-K). These parameters and warfarin levels were measured before and following a single dose of warfarin given to five patients when hyperthyroid and again when euthyroid. Hyperthyroidism was associated with lower activity of factor II and a shorter PTT-K. Warfarin produced a greater fall in factors II and VII and a greater increase in PTR and PTT-K in the hyperthyroid state than in the euthyroid state. The enhanced response to warfarin in hyperthyroidism was, however, relatively greater for the PTR than for the PTT-K. In order to produce adequate protection against intravascular thrombosis by a suitable prolongation of the PTT-K, it may be necessary in hyperthyroid patients to extend the PTR beyond the normal therapeutic range.

Aged↗
PubMed1986

SimulTRAC simultaneous radioimmunoassay of thyrotropin and free thyroxin evaluated.

We assessed the analytical and diagnostic performance of a dual-isotope RIA for thyrotropin (TSH) and free thyroxin (FT4) in serum. The mean interassay CVs for these analytes were 7.9% and 5.0%, respectively. The mean minimum detection limit for TSH was 0.25 milli-int. unit/L, the mean analytical recovery 110%. There was good agreement with values for TSH and FT4 measured by alternative RIA procedures. Euthyroid patients were well distinguished from those with overt thyroid disease, although there was a small overlap in the case of TSH. Combining the two results better discriminated these categories and identified those patients with subclinical thyroid disease who had abnormal TSH concentrations but FT4 concentrations within reference limits. Euthyroid women taking estrogen-containing oral contraceptives had normal results for TSH and FT4, as did most pregnant women studied. During the third trimester of pregnancy, TSH concentrations of women with low FT4 concentrations were within reference limits. Similarly, euthyroidism was confirmed in patients with low FT4 due to nonthyroidal illness by the simultaneous finding of a normal TSH concentration.

Adult↗
PubMed1985

Limitations of new thyroid function tests in pregnancy.

Sensitive immunoradiometric assays (IRMA) for TSH and radioimmunoassay (RIA) kits for free thyroid hormones (fT4, fT3) are becoming increasingly used for routine thyroid investigations. We have assessed these tests in 93 euthyroid pregnant women. Mean fT4 and fT3 values decreased with gestation by 24-27% and 14-35%, respectively, using several analogue RIA kits. Some patients had free hormone values which fell below the reference range derived from non-pregnant euthyroid patients. By contrast, the fT4 concentrations measured by direct equilibrium dialysis fell by only 16% with all values within the reference range. Serum non-esterified fatty acid (NEFA) levels (non-fasting) did not correlate with fT4 and fT3 but a spurious effect of serum albumin levels on the free hormone kits was suggested. TSH results showed that the majority of subjects had lower values measured by IRMA than by RIA. Three patients had basal TSH (IRMA) below the mean detection limit of the assay; this could have been falsely interpreted as indicating hyperthyroidism. We conclude that, as with longer established thyroid function tests, special care must be taken in interpreting results of these new thyroid function tests in pregnancy.

Fatty Acids, Nonesterified↗
PubMed1985

Raised plasma glutathione S-transferase values in hyperthyroidism and in hypothyroid patients receiving thyroxine replacement: evidence for hepatic damage.

Using plasma glutathione S-transferase measurements hepatocellular integrity was assessed in groups of hyperthyroid and hypothyroid patients before and after treatment. Ten of 14 hyperthyroid patients had clearly raised plasma glutathione S-transferase values at presentation and in each patient treatment with either iodine-131 or carbimazole resulted in a significant fall in glutathione S-transferase. The eight hypothyroid patients had normal glutathione S-transferase values at presentation and all showed a significant increase in these after thyroxine replacement therapy. In three of these patients in whom standard doses of replacement therapy were associated with a raised free thyroxine (T4) concentration but normal total and free triiodothyronine (T3) values glutathione S-transferase was increased. Similar though less consistent changes were seen in the results of standard chemical tests of liver function. It is concluded that hyperthyroidism may produce subclinical liver damage in a high proportion of patients and that this resolves with effective treatment. More important, the data suggest that hypothyroid patients receiving thyroxine replacement therapy may have similar subclinical liver damage. Patients receiving thyroxine should be monitored by the measurement of free, not total hormone concentrations, and in those in whom free T4 is raised the dose of thyroxine should be reduced. It would also be expedient to include periodic biochemical assessment of liver function in patients receiving thyroxine.

Adult↗
PubMed1985

A new strategy for thyroid function testing.

In view of the increasing number of in-vitro tests of thyroid function, rationalization of the biochemical assessment of patients with suspected thyroid disease was attempted. In addition to clinical examination of 285 consecutive new referrals to a thyroid clinic, measurements were made of serum total and free triiodothyronine (T3) and thyroxine (T4) and of thyrotropin (TSH) by radioimmunoassay before and 20 min after thyrotropin-releasing hormone (TRH) and basal TSH by immunoradiometric assay (IRMA). Analysis of these results demonstrated that: (i) a detectable and normal TSH (IRMA) result indicates that the patient is euthyroid and obviates the need for measurement of thyroid hormones and (ii) a raised or undetectable TSH (IRMA) level should be followed by measurement of free T4 (and rarely also free T3) to distinguish between subclinical and overt hypothyroidism and hyperthyroidism. This policy would considerably reduce the number of in-vitro thyroid function tests without resulting in either a delay in diagnosis or a reduction in its accuracy.

Adolescent↗
PubMed1985

Thyroid enlargement.

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Diagnosis, Differential↗
PubMed1985

End-organ responses to thyroxine therapy in subclinical hypothyroidism.

We studied variables known to change with thyroid hormone status in 18 patients with subclinical hypothyroidism before and during treatment with thyroxine in a dose sufficient to restore the plasma TSH response to TRH to normal. There was an associated increase in both plasma total T4 and free T4 within the normal range but plasma total T3 and free T3 were unchanged. As a result of thyroxine treatment there was a small but significant increase (P less than 0.05) in left ventricular ejection fraction (LVEF) with maximal exercise but no significant changes in LVEF at rest and moderate exercise, continuously monitored mean sleeping heart rate, day/night ratios of urinary sodium excretion, peripheral nerve conduction velocities, fasting serum triglycerides, total cholesterol (TC), high density lipoproteins (HDL) or TC/HDL ratios. On this evidence we do not consider that thyroxine replacement therapy is indicated in patients with subclinical hypothyroidism.

Adult↗
PubMed1985

Accuracy and precision of five analog radioimmunoassays for free thyroxin compared.

We compared the precision of free thyroxin (FT4) measurements by kits involving analog RIA and the use of antibody-coated tubes (Becton Dickinson and Coat-A-Count), magnetic separation (Amerlex Magnetic and Corning Magic), or centrifugation of antibodies linked to solid beads (Amerlex). Results of kits with magnetic separation were the most reproducible. Amerlex, Amerlex Magnetic, and Becton Dickinson kits gave values comparing best with those obtained by direct equilibrium dialysis. Coat-A-Count and Corning Magic results differed significantly from dialysis values, both for patients' samples and kit standards. The kits had equal diagnostic efficiency in patients with suspected thyroid disease. On measurement of FT4 some patients were reclassified from "subclinical thyroid disease" to "overt disease." Most patients with triiodothyronine thyrotoxicosis had increased FT4. Several kit values were low for pregnant women and patients with nonthyroidal illness but the Amerlex and Amerlex Magnetic assays had fewer low results. The Amerlex Magnetic FT4 assay gave the best precision, agreement with the reference method, and diagnostic efficiency.

Dialysis↗
PubMed1985

Left ventricular performance in subclinical hypothyroidism.

Normal plasma thyroid hormones with elevation of thyrotrophin levels in asymptomatic patients is known as subclinical hypothyroidism. Radionuclide angiography was used to study left ventricular function in 10 such patients before and after establishment of normal thyrotrophin levels with thyroxine. Resting left ventricular ejection fraction was similar in both states but exercise left ventricular ejection fraction was less in the subclinical hypothyroid (61 +/- 3 per cent) compared with the euthyroid (68 +/- 3 per cent; p less than 0.025) state. Sodium nitroprusside caused similar increases in resting cardiac output but in subclinical hypothyroidism this resulted from a large increase in heart rate (26 +/- 4 beats/min) and reduction in stroke volume (11 +/- 4 per cent) whereas in the euthyroid state, the heart rate increment was less (14 +/- beats/min) and stroke volume was unchanged. Analysis of left ventricular pressure-volume relationships at end-systole during exercise showed a steeper pressure-volume slope in the euthyroid compared with the subclinical hypothyroid state (p less than 0.05). Subtle impairment of left ventricular function is detectable in subclinical hypothyroidism and may justify use of hormone replacement.

Adult↗
PubMed1984

A sensitive immunoradiometric assay for serum thyroid stimulating hormone: a replacement for the thyrotrophin releasing hormone test?

The value as a thyroid function test of a new, rapid, and highly sensitive immunoradiometric assay for thyroid stimulating hormone (TSH) was assessed in 188 consecutive new patients with suspected hyperthyroidism. The diagnosis was made on clinical grounds and on the basis of serum total triiodothyronine and thyroxine concentrations and the response of TSH to thyrotrophin releasing hormone (TRH) as measured by radioimmunoassay. In all except one patient the basal TSH concentration by immunoradiometric assay predicted the response of TSH by radioimmunoassay to TRH, an undetectable value being recorded in patients with a subnormal response and a measurable value in those with a normal test result. This clear relation was not observed for basal TSH concentrations as measured by radioimmunoassay. In a series of 39 hospital inpatients with acute or chronic non-thyroidal illness, of whom 11 had low concentrations of total thyroxine or triiodothyronine, or both, basal TSH concentrations were detectable by both radioimmunoassay and immunoradiometric assay in all cases and were associated with normal responses to TRH. The immunoradiometric assay for TSH, which is commercially available, may therefore obviate the need for the more time consuming TRH test and simplify the approach to thyroid function testing in patients with suspected hyperthyroidism.

Adult↗
PubMed1984

Graves' disease and atrial fibrillation: the case for even higher doses of therapeutic iodine-131.

Seventy five consecutive patients with Graves' disease complicated by atrial fibrillation were given a large single therapeutic dose of 600 MBq (16.2 mCi) iodine-131 in an effort to control their hyperthyroidism rapidly and thus restore sinus rhythm. Patients were initially followed up every three months after treatment and then at yearly intervals. The mean period of follow up was 3.1 years. A total of 44 of the patients became hypothyroid and 31 euthyroid, and 33 (75%) and 14 (45%) of these patients, respectively, reverted to sinus rhythm (p less than 0.01). Of the 33 who became hypothyroid and reverted to sinus rhythm, 30 had developed the hypothyroidism within six months after treatment. These results are a strong case for increasing the dose of radioiodine in patients with Graves' disease complicated by atrial fibrillation in an effort to speed the onset of thyroid failure and thus maximise the rate of reversion to sinus rhythm.

Adult↗
PubMed1984

How effective is external pituitary irradiation for growth hormone-secreting pituitary tumors?

Forty-six patients with GH-secreting pituitary tumours were treated with conventional external pituitary irradiation through two opposed fields to a total dose of 3750 cGy over 15 fractions. Thirty-patients received external radiotherapy as primary treatment and 16 received radiotherapy combined with pituitary surgery. The mean (+/- SD) serum GH in the former group was 74.3 +/- 74.8 mU/l before treatment, falling by 28% per year over 0-5 years and by 16% per year over 0-20 years. The mean (+/- SD) serum GH in the latter group was 265.4 +/- 209.3 mU/l before treatment, falling by 76% in the first year--a direct result of surgical removal of tumour--then by 30% per year over 1-5 years and 16% per year over 1-20 years. Progressive failure of normal anterior pituitary function developed by 10 years, with variable loss of gonadotrophin, corticotrophin and thyrotrophin function. The respective figures for patients treated with radiotherapy alone were 47.4, 29.6 and 16.0% and for the combined group were 70.2, 53.9 and 38.1%. Whilst external pituitary irradiation appears to reduce serum GH concentrations in patients with GH-secreting pituitary tumours the major disadvantages of this form of treatment are the time taken to achieve a cure and the high incidence of hypopituitarism. Nevertheless there did not appear to be any other serious side effects.

Acromegaly↗
PubMed1984

Delayed recovery of left ventricular function after antithyroid treatment. Further evidence for reversible abnormalities of contractility in hyperthyroidism.

Sequential measurements of systolic time intervals, left ventricular dimensions, and the derived indices of contractility were undertaken at rest and during isometric exercise in 15 hyperthyroid patients before, during, and after antithyroid treatment. At rest hyperthyroidism was characterised by a shortened pre-ejection period and increased velocity of circumferential shortening of the left ventricle. During isometric exercise, however, the pre-ejection period increased significantly beyond that predicted for normal subjects, and the velocity of circumferential fibre shortening fell by 30%. In contrast, both the pre-ejection period and the velocity of circumferential fibre shortening were unchanged during exercise after a stable euthyroid state had been achieved for at least three months. Comparison between exercise responses and thyroid status during antithyroid treatment showed that a biochemical euthyroid state may be achieved many weeks before normalisation of contractile response to exercise. These findings support the hypothesis of reversible depression of left ventricular function in hyperthyroidism. Responses at rest principally reflect the peripheral actions of thyroid hormone excess.

Adult↗