Search

C CLARKE, CG BRENNAN, K RODGERS, RM DWYER, PPA SMYTH ENDOCRINE LABORATORY, DEPARTMENT OF MEDICINE AND THERAPEUTICS, UNIVERSITY COLLEGE DUBLIN, IRELAND he demonstration in extrathyroidal human tissues of the sodium iodide symporter (NIS) has raised the possibility that 1311, commonly used as a systemic therapeutic ablative agent in hyperthyroidism and thyroid cancer, might be applied in the treatment of tumours in other NISexpressing tissues such as human breast cancer. Thyroidal transport of 1311 is known to be proportional to circulating stable I and the aim of this study was to determine how stable I (KI) would effect such transport in human breast cancer cell lines MDA-MB-231, MCF-7 and in FRTL-5 thyroid cells. All cells were incubated with KI (01 00mM) for 72 hours after which 1Th I was added . Incubation and uptake of 'l by cells was counted every four hours. Timed efflux of '^I was measured every five minutes. KI in the incubation medium blocked 1251 uptake in a dose-dependent manner in the E receptor positive MCF7 cell line. The effect was less marked in the E receptor negative MDA-MB-231 with significant uptake being maintained even at an I concentration of 50mM. A similar blockade was seen in the FRTL-5 cells with maximum uptake blockade of 25mM I. The rate of efflux of 15I was similar in both MCF-7 and MDA-MB-231 cell lines with a tin of 35 and 40 minutes respectively. In contrast, efflux from the FRTL-5 cells was faster (tire=15 mins). As the human breast has a much lower avidity for I than the thyroid, control of dietary intake would assume even greater importance in radioactive iodine treatment of breast tumours or their metastases.

Thyroid tests are done in acutely ill patients who often have confusing transient thyroid abnormalities, despite a lack of clarity about intervention and cost benefit. A retrospective analysis of patients admitted to the Medical Assessment Unit (MAU) was undertaken in 2004 to assess the frequency and utility, pattern of abnormalities and cost of thyroid testing. Guidelines were issued and the audit was repeated in 2008. 53.8% of 1593 subjects were offered thyroid tests in 2004 with a significant reduction to 21.7% of 1176 in 2008 (p0.001). Free T4 or TSH was outside the reference range in 11.2% (2004) and 7.5% (2008) (p=0.10) and low TSH (52.7% in 2004 and 64.3% in 2008) was commonly combined with normal free T4. Appropriate indications for testing were documented in 43.9 vs 73.7% of patients with abnormal thyroid results (p=0.004) and in 14.3 vs 16% (2004 vs 2008) of a random sample of subjects with normal thyroid results, respectively (p=0.77). Documentation of intervention (25.5. vs 92.9%; p=0.001) and follow-up (45.5 vs 85.7%; p=0.001) had also improved significantly in 2008. We have demonstrated a significant reduction in thyroid testing in acutely ill patients after audit and the issue of guidelines. We currently recommend thyroid tests only in those with previous thyroid disease, the presence of clinical features and risk factors for thyroid disease, the use of relevant drugs, and unexplained tachydysrhythmias. The difficulties in interpreting results, the lack of clarity about intervention and follow up and possible cost savings would argue against an unrestricted policy.

The value and practice of thyroid radionuclide imaging in the diagnosis and management of hyperthyroidism is unsettled. Our objectives were to determine the influence of thyroid uptake and scintigraphy on the diagnosis of hyperthyroidism and the prediction of outcome following radioiodine therapy.We reviewed records and scintigraphic studies on 881 hyperthyroid patients carried out between 2000 and 2007. The agreement between the clinical and scintigraphic diagnosis was evaluated by kappa statistics. We determined the relationship between 4-h (123)I uptake and the outcome of (131)I treatment in 626 patients. A multiple logistic regression model was used to determine variables influencing treatment outcome in 1 year.The diagnostic categories were Graves' disease (GD, n = 383), toxic multinodular goitre (n = 253), solitary toxic nodule (n = 164) and Graves' disease coexisting with nodules (n = 81). The mean age of the patients was 58 +/- 17, (M:F 160:721). There was good agreement between clinical and scintigraph diagnosis (K = 0.60, 95% CI 0.57-0.64, P0.001); and they were correctly matched in 74%; mismatched in 6% and indeterminate in 20% of patients. Treatment outcome was not associated with scintigraph diagnosis (P = 0.98) or radioiodine uptake at 4 h (P = 0.2). The use of antithyroid medications before treatment predicted treatment failure (odds ratio 2.0, 95% CI 1.2-3.6, P = 0.01).Thyroid scintigraphy and uptake studies did not influence diagnosis or treatment outcomes in most cases of hyperthyroidism. Our findings in this retrospective study do not justify their routine use. Selective scanning will reduce cost and exposure to radioisotopes without compromising diagnostic accuracy or treatment outcomes.

Although gestational hyperthyroidism is uncommon (0.2%), hypothyroidism (autoimmune disease or suboptimal iodine intake) occurs in 2.5% of women and is predictive of reduced neonatal and child neuropsychological development and maternal obstetric complications. Postpartum thyroid dysfunction (PPTD) occurs in 5-9% of women and is associated with antithyroid peroxidase antibodies (antiTPOAb) in 10% of women in early pregnancy. Therefore, screening for thyroid dysfunction in pregnancy should be considered. T4 and thyroid stimulating hormone measurements could be used to screen for hypothyroidism, which would require levothyroxine intervention treatment. T4 supply is crucial to fetal nervous system maturation; currently, the recommended daily iodine intake is 200 microg, and this is not always achieved, even in the UK. At present, a randomised prospective trial is ongoing to provide the evidence base for this screening strategy. Meanwhile, it is reasonable to (a) optimise iodine nutrition during pregnancy; (b) ascertain women with known thyroid disease; (c) identify women at increased risk of thyroid disease-for example, those with other autoimmune diseases. PPTD can be predicted by measurement of antiTPOAb in early gestation.

We previously reported a high prevalence of raised thyroglobulin autoantibodies (TgAb) in apparently healthy Sri Lankan schoolgirls following salt iodination. To characterize these antibodies further we determined the epitopes on thyroglobulin (Tg) with which they react and compared these with serum obtained from both healthy subjects and established autoimmune thyroid disease (AITD) patients from the UK. To extend our study to a wider population within Sri Lanka, we in addition determined the epitopes recognized by a group of AITD patients selected from a thyroid clinic in Sri Lanka, as well as apparently healthy female Sri Lankan tea workers of distinct ethnicity from the schoolgirls and AITD patients.Sri Lankan schoolgirls (n = 282) and adult female tea estate workers (n = 208) were examined for thyroid autoimmune markers. Sera with high TgAb (98 kIU/l) were selected from these two groups (n = 36 and 45, respectively) to study epitope-binding patterns. We also examined the sera from 16 AITD patients attending a thyroid clinic in Colombo, 16 patients with AITD from the thyroid clinic at the University Hospital of Wales and 16 sera from healthy control UK women with no evidence of thyroid disease. To determine the epitopes on Tg recognized by the subjects' TgAb, we employed a panel of Tg mouse monoclonal antibodies labelled with alkaline phosphatase in a competitive enzyme-linked immunosorbent assay reaction with the subjects' serum.A majority of the Sri Lankan schoolgirls did not react with the immunodominant epitopes and did not differ significantly from healthy subjects from the UK in their Tg epitope recognition pattern. On the other hand, tea estate workers and Sri Lankan AITD patients recognized typical autoimmune thyroid disease epitopes and, in addition, recognized a separate cluster not previously associated with either the autoimmune state or the healthy state. The significance of this cluster requires further clarification.