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Biomedical subjects

J Daykin

Publications and source records attributed to J Daykin.

28 records · Page 2Linked to original sources

Cardiac hypertrophy as a result of long-term thyroxine therapy and thyrotoxicosis.

OBJECTIVES: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. DESIGN: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). METHODS: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. RESULTS: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs. CONCLUSIONS: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence of significant changes in heart rate, blood pressure, and left ventricular systolic function is consistent with a direct trophic effect of thyroid hormone on the myocardium. The presence of left ventricular hypertrophy determines that further studies are essential to assess cardiovascular risk in patients taking thyroxine long term.

Adult↗

Radioiodine therapy compared in patients with toxic nodular or Graves' hyperthyroidism.

In view of uncertainty regarding the most appropriate radioiodine dose for patients with hyperthyroidism due to toxic nodular disease or Graves' disease, we prospectively studied outcome in patients with these disorders given a single 5 mCi (185 MBq) dose of radioiodine. We studied 103 patients receiving their first radioiodine dose; 44 with toxic nodular hyperthyroidism and 59 with Graves' hyperthyroidism. Thyroid status (off anti-thyroid drug therapy) at 6 and 12 months after radioiodine was related to diagnosis, use of carbimazole before or after radioiodine, and physical and biochemical findings. At 6 months, persistent hyperthyroidism was less frequent in toxic nodular disease than in Graves' disease (34.1% vs. 55.9%, p < 0.05); hypothyroidism was also less frequent (11.4% vs. 27.1%, p < 0.05). Those with persistent hyperthyroidism at 6 months were given a second (10 mCi, 370 MBq) dose of radioiodine. At 12 months after the first dose, 80.6% of the group with toxic nodular hyperthyroidism were either euthyroid or hypothyroid, and 74.5% of those with Graves' disease were euthyroid or hypothyroid, the rate of hypothyroidism again being less in toxic nodular disease (19.4% vs. 58.8%, p < 0.05). Logistic regression and stepwise discriminant analysis demonstrated that 'cure' (euthyroidism or hypothyroidism) at 6 months was related to serum free T4 at presentation (p < 0.001) and administration of carbimazole before or after radioiodine (p < 0.001) (severe hyperthyroidism and carbimazole increasing the likelihood of persistent hyperthyroidism) but was not related to the diagnosis of toxic nodular or Graves' hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Bone mineral density in thyroxine treated females with or without a previous history of thyrotoxicosis.

OBJECTIVE: The results of studies examining the influence of T4 therapy upon bone mineral density (BMD) are conflicting. This conflict may, in part, reflect inclusion of patients with varying thyroid disorders. We have therefore examined the influence of preceding thyroid history and T4 therapy on BMD. DESIGN: Case-control studies of patients on long-term T4 therapy who have or have not previously received radioiodine treatment for thyrotoxicosis, as well as previously thyrotoxic patients who have not required T4 replacement. PATIENTS: Twenty-seven premenopausal and 60 postmenopausal females with a past history of thyrotoxicosis and subsequent T4 treated hypothyroidism (group 1), 39 post-menopausal females with a past history of radioiodine treated thyrotoxicosis not receiving T4 (group 2) and 22 post-menopausal females with primary hypothyroidism on T4 (group 3). Female controls individually matched to patients by age and menopausal status. MEASUREMENTS: BMD measured by dual-energy X-ray absorptiometry. Serum biochemistry and tests of thyroid function. RESULTS: No significant differences were found in femoral or lumbar spine BMD measurements between premenopausal patients and controls in group 1 or between group 2 patients and controls. Measurements of BMD at all sites were lower in post-menopausal patients in groups 1 and 2 than in controls; when allowance was made for differences in BMD due to body mass index by analysis of variance, significant reductions in femoral trochanter BMD (3.9%, P < 0.05) and lumbar spine (5.6-8.5%, P < 0.01) BMD results were found in post-menopausal females in group 1 and reductions in femoral trochanter (3.9%, P < 0.01), Ward's triangle (5.6%, P < 0.05) and lumbar spine (8.5%, P < 0.01) BMD results in group 2. Separate analysis of BMD results of those with normal or reduced serum TSH did not affect outcome. BMD measurements were not significantly correlated with duration of T4 therapy, T4 dose, or serum free T4 or TSH in any patient group. CONCLUSIONS: Thyroxine therapy alone does not represent a significant risk factor for loss of bone mineral density but there is a risk of bone loss in post-menopausal (but not premenopausal) females with a previous history of thyrotoxicosis treated with radioiodine.

Absorptiometry, Photon↗

Radioiodine therapy for hyperthyroidism in young patients--perception of risk and use.

Although radioiodine is increasingly the treatment of choice in hyperthyroidism, there are regional differences in its use which reflect, in part, concerns regarding safety. We investigated attitudes amongst general practitioners and consultant physicians to the role of radioiodine therapy, and reviewed our own radioiodine prescribing in patients aged less than 40 to elucidate any influence of age and/or sex. We surveyed general practitioners in the former Central Birmingham Health District and consultant physicians in the West Midlands Region to investigate treatment preferences in hyperthyroidism and perceived risk from radioiodine of hypothyroidism, carcinogenesis and infertility. Of 230 general practitioner and 130 consultant physician respondents, less than 1% considered radioiodine the treatment of choice in a 25-year-old female presenting with hyperthyroidism. At relapse after antithyroid drug treatment in a 25-year-old female, only 16.5% of general practitioners and 23.9% of physicians advocated radioiodine, the greatest number preferring partial thyroidectomy. For a 65-year-old at presentation, 49.1% of general practitioners and 62.3% of physicians considered radioiodine the treatment of choice. More than 10% failed to note the risk of hypothyroidism following radioiodine, while 11-34% perceived increased risk of malignancy or infertility. Review of our own practice demonstrated that of 100 patients given radioiodine, 94% were cured of hyperthyroidism when reviewed at a mean of 2.4 years from latest treatment, 70% being hypothyroid. Females given radioiodine were treated less promptly following diagnosis of hyperthyroidism than males (2.2 +/- 0.26 years vs. 1.6 +/- 0.4) and were more likely to have received a preceding course of antithyroid drugs (78% vs. 57%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Thyroxine replacement therapy and circulating lipid concentrations.

OBJECTIVE: Hypothyroidism is a common disorder and while the association of overt hypothyroidism with hypercholesterolaemia is clear, the effect upon lipids of the minor abnormalities of thyroid function often found in those receiving T4 replacement therapy is unclear. The aim of the present studies was to define in those with hypothyroidism the effect upon circulating lipids of subtle changes in thyroid status, indicated by serum TSH values below or above the normal range. DESIGN: (i) Prospective study of short-term T4 treatment of those with subclinical hypothyroidism. (ii) Cross-sectional study of long-term T4 treatment, comparing non-T4 treated controls and T4 treated patients with serum TSH values either below or within the normal range. PATIENTS: Short-term T4 therapy was examined in 11 post-menopausal females with subclinical hypothyroidism (high TSH, normal free T4) studied before therapy and 6 weeks after T4 at incremental doses (50, 100, 150 micrograms/day). Long-term T4 treatment for hypothyroidism was investigated in 105 females on therapy for at least 1 year compared with 105 controls matched for age and menopausal status. MEASUREMENTS: Fasting levels of total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol and HDL subfractions were determined in patients and controls. RESULTS: (i) T4 treatment of subjects with subclinical hypothyroidism resulted in reductions in total and LDL cholesterol with increasing T4 dose (P < 0.001). Comparison of lipid results pretreatment with those when TSH was restored to normal revealed no significant difference in lipids; in contrast, comparison of lipids in those with normal TSH compared with the same subjects when TSH was suppressed revealed reductions in total and LDL cholesterol. (ii) Long-term T4 treatment was associated with a reduction in total and LDL cholesterol measurements in those over 55 years receiving suppressive doses of T4 but no significant difference in lipids in those with normal serum TSH compared with non-T4 treated controls. CONCLUSION: Effects of T4 upon lipid measurements suggest that patients with subclinical hypothyroidism should receive replacement therapy. Doses of T4 which suppress TSH to below normal may have a more significant influence upon lipids than doses of T4 which restore TSH to the normal range.

Aged↗

Long-term thyroxine treatment and bone mineral density.

Studies of the effect of thyroxine replacement therapy on bone mineral density have given conflicting results; the reductions in bone mass reported by some have prompted recommendations that prescribed doses of thyroxine should be reduced. We have examined the effect of long-term thyroxine treatment in a large homogeneous group of patients; all had undergone thyroidectomy for differentiated thyroid cancer but had no history of other thyroid disorders. The 49 patients were matched with controls for age, sex, menopausal status, body mass index, smoking history, and calcium intake score; in all subjects bone mineral density at several femoral and vertebral sites was measured by dual-energy X-ray absorptiometry. Despite long-term thyroxine therapy (mean duration 7.9 [range 1-19] years) at doses (mean 191 [SD 50] micrograms/day) that resulted in higher serum thyroxine and lower serum thyrotropin concentrations than in the controls, the patients showed no evidence of lower bone mineral density than the controls at any site. Nor was bone mineral density correlated with dose, duration of therapy, or cumulative intake, or with tests of thyroid function. There was a decrease in bone density with age in both groups. We suggest that thyroxine alone does not have a significant effect on bone mineral density and hence on risk of osteoporotic fractures.

Absorptiometry, Photon↗

The significance of TSH values measured in a sensitive assay in the follow-up of hyperthyroid patients treated with radioiodine.

Use of sensitive assays for TSH in the follow-up of patients treated with radioiodine (131I) for thyrotoxicosis has led to questions regarding the significance of abnormal TSH values found in association with normal circulating thyroid hormone levels, especially TSH results below normal. We have investigated the relationship between serum TSH and the likelihood of maintenance of euthyroidism, as well as the relationship between serum TSH and free T4, in 389 subjects treated with 131I 2-35 years previously who had free T4 and free T3 values within the normal range and who were not receiving thyroxine or antithyroid therapy. In those with undetectable TSH (less than 0.05 mU/L), TSH remained undetectable in 54.5% at 1 yr but rose to detectable or normal values in the remainder. In those with low but measurable TSH (0.05-0.5 mU/L), results were similar at 1 yr in 47.5% and returned to normal in 45%. No patient with a TSH value below normal became hypothyroid (defined as a reduction in serum free T4). In those with normal TSH (0.5-5.0 mU/L) at time 0, TSH remained normal in 83%, fell in 4% and became elevated in 13%. The yr 1 incidence of hypothyroidism was 1%; one patient became thyrotoxic. In those with TSH values above normal (5.0-15.0 mU/L), TSH remained elevated in 90.6%; the incidence of hypothyroidism was 14.5% in yr 1. The small risk of development of hypothyroidism in those with subnormal or normal TSH indicates that biochemical testing is not essential for 1-2 yr in such patients; this contrasts with a need for repeat testing within a period not exceeding 1 yr in those with elevated TSH. The relationship between serum-free T4 and TSH suggests that TSH results outside the normal range reflect thyroid hormone excess or deficiency. Persistence of undetectable TSH values during follow-up and the observation of higher free T4 at time 0 in those whose TSH remained undetectable compared with those whose TSH rose suggest that undetectable TSH concentrations are of greater significance than low but detectable values.

Adult↗

Long-term follow-up of treatment of thyrotoxicosis by three different methods.

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%. At 5 years, 18% were hypothyroid, the prevalence rising to 42% at 20 years. Of 504 patients treated with an empirical 131I dose and followed for at least 5 years, thyrotoxicosis was controlled by a single dose in 89.7%. The rate of hypothyroidism at 5 years (38.5%) was higher than that found in the calculated dose group. A minimum 10-year follow-up was achieved for 295 surgically treated patients; thyrotoxicosis was controlled in 89.2%. The prevalence of hypothyroidism (2% at 5 years, 27.5% at 20 years) was lower than that found after 131I, whether given by calculated or empirical dose. Each of the treatments employed resulted in an acceptable rate of cure of thyrotoxicosis. If maintenance of euthyroidism is the major objective, our findings suggest that surgery represents the treatment of choice. Furthermore, calculated dose 131I administration has advantages in terms of risk of hypothyroidism over empirical dose treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗