Prognostic significance of thyroglobulin antibody epitopes in differentiated thyroid cancer.

CONTEXT: Thyroglobulin antibodies (TgAbs) are surrogate markers of disease recurrence or persistence in differentiated thyroid cancer (DTC). However, the prognostic significance of TgAb heterogeneity in DTC has not been investigated. OBJECTIVE: To evaluate the relationship between TgAb epitope specificities and clinical outcomes in DTC patients. DESIGN: We studied 61 TgAb-positive patients with DTC, post-thyroidectomy and remnant ablation (7 males, 54 females; age-range 16-80 years, median follow-up duration 8.9 years). TgAb epitope reactivities were mapped using a panel of 10 thyroglobulin (Tg) monoclonal antibodies delineating six antigenic Tg clusters in competitive ELISA studies. Sera from 45 patients with Hashimoto's thyroiditis (HT) and 22 TgAb-positive healthy subjects served as autoimmune and healthy controls. Tg was measured by immunoradiometric assay (IRMA), electrochemiluminescence immunoassay (ECLIA), and RIA, while TgAbs was measured by ELISA and ECLIA methods. RESULTS: Samples from 26 DTC patients showed TgAb epitope restriction similar to HT patients, while 35 patients exhibited nonspecific reactivity comparable to healthy controls. DTC patients with epitope restriction had higher rates of recurrent/persistent disease (81% vs 17%, P < .001), higher median TgAb concentration (887.0 vs 82.0 kIU/L; P < .001), and a higher prevalence of thyroid lymphocytic infiltration (71.4% vs 26.8%; P < .001) compared to patients with nonspecific reactivity. Samples with epitope restriction also had a lower median Tg-IRMA/RIA ratio (3.0% vs 36.0%; P < .001) denoting greater degrees of Tg assay interference. CONCLUSIONS: TgAb epitope restriction is associated with a less favorable prognosis than nonspecific reactivity in DTC patients. TgAb epitope specificities may have prognostic value in DTC.

Targeted thyroid testing in acute illness: achieving success through audit.

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 (p<0.001). 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 utility of radioiodine uptake and thyroid scintigraphy in the diagnosis and management of hyperthyroidism.

BACKGROUND AND OBJECTIVES: 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. PATIENTS AND DESIGN: 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. RESULTS: 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, P < 0.001); 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). CONCLUSION: 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.

Restricted thyroglobulin antibody epitope specificities in subjects with type 1 diabetes mellitus.

OBJECTIVES: Following iodisation in Sri Lanka we observed a high prevalence of thyroglobulin antibodies (TgAbs) in type 1 diabetic (T1DM) patients. The clinical significance of these TgAbs is uncertain. We sought to obtain a detailed epitope analysis of TgAbs in T1DM patients recruited from diabetes clinics and to compare these with TgAb epitope specificities in patients with autoimmune thyroid disease (AITD) and healthy individuals in that country. DESIGN AND METHODS: We used a panel of 10 Tg-MAbs in competitive ELISA reactions in a prospective study of subjects recruited from Colombo, to determine the epitopes recognised by TgAb-positive patients with T1DM (n=58, 34F:24M, median age 16 years), AITD patients (n=42, 33F:9M, median age 37 years) and healthy subjects (n=50, 39F:11M, median age 27 years). The outcomes were a comparison of reactivity with six Tg clusters (I-VI) in these subjects, and the relation of epitope specificity patterns with free thyroxine and TSH. RESULTS: Patients with T1DM and AITD but not healthy control subjects preferentially recognised the immunodominant clusters, I, III and IV. Patients with these narrow epitope specificities had higher median TSH levels (1.60 vs 1.06; P=0.01), and were more frequently positive for antibodies to thyroid peroxidase than those with broad specificities (52.3 vs 7.1%; P=0.004). CONCLUSIONS: The TgAb epitope specificities in euthyroid Sri Lankans with T1DM are similar to AITD patients. TgAb epitope studies may potentially identify T1DM patients at risk of thyroid dysfunction.

Peripheral cytokine expression in autoimmune thyroiditis: effects of in vitro modulation by rosiglitazone and dexamethasone.

BACKGROUND: In Hashimoto's thyroiditis (HT), there is evidence for activation of peripheral T-lymphocytes that predominantly express a T helper 1 (T(H)1) cytokine bias. However, the immunomodulatory factors involved in regulating this response have so far received scant attention. In this study, we examine the effects of the glucocorticoid, dexamethasone, and the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligand, rosiglitazone on the expression of interferon (IFN)-gamma (T(H)1) and interleukin (IL)-4 (T(H)2) by activated peripheral CD4(+) and CD8(+) lymphocytes in patients with HT (n = 10) and healthy control subjects (n = 12). METHODS: Peripheral blood mononuclear cells (PBMC) were stimulated in vitro with phorbolmyristate acetate (PMA) and ionomycin in the presence or absence of varying doses of dexamethasone and rosiglitazone (0.01 microM, 1.0 microM, and 100 microM). Cytokine expression was determined by flow cytometry. RESULTS: CD4(+) and CD8(+) IFN-gamma expression was greater in HT than controls (14.87 versus 9.25; p < 0.05 and 21.34 versus 10.16; p < 0.01, respectively). A dose-dependent inhibition of IFN-gamma expression was seen with dexamethasone and rosiglitazone. Inhibition of CD4(+) and CD8(+) IFN-gamma expression with both dexamethasone and rosiglitazone was greater in control subjects than in patients (p < 0.05). There was no significant difference in IL-4 expression between patients and control groups and its expression remained unaffected by either compound. CONCLUSIONS: We show that CD4(+) and CD8(+) T lymphocytes from HT patients express a type 1 cytokine bias that is significantly more resistant to in vitro modulation by rosiglitazone and dexamethasone. Further studies are needed to clarify if this resistance plays a role in the pathogenesis of autoimmune thyroid disease (AITD).

Management of thyroid disorders.

Autoimmune thyroid disease is the predominant form of thyroid dysfunction in the developed world. Although its precise cause is currently unclear, principles of management have been established. There is a vigorous debate about the management of the increasingly commonly recognised subclinical forms of thyroid dysfunction despite recent recommendations. Nodular thyroid disease and thyroid carcinoma have received wide attention. The effects of drugs and pregnancy on thyroid function have also been investigated widely. This short review attempts to give an overview and clarify the current management of common thyroid disorders.

Islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes from Sri Lanka.

AIMS: The prevalence of islet cell, thyroid, adrenal and celiac disease related autoantibodies in patients with Type 1 diabetes mellitus (Type 1 DM) from Sri Lanka is described. DESIGN AND METHODS: Autoantibodies to glutamic acid decarboxylase 65 (GAD65Ab), protein tyrosine phosphatase IA-2 (IA-2Ab), insulin (IAAb), thyroglobulin (TgAb), thyroid peroxidase (TPOAb), TSH receptor (TRAb), 21-hydroxylase (21-OHAb) and tissue transglutaminase (tTGAb) were measured in 122 Type 1 DM patients who had low C-peptide activity or were >20 yr old at the time of diagnosis and in 100 non-diabetic blood donors. RESULTS: GAD65Ab and/or IA-2Ab were present in 74/122 (60.7%) Type 1 DM subjects with a significantly higher prevalence compared to non-diabetic controls (no. 100) (GAD65Ab-59 vs 4%; IA-2Ab-14 vs 0%; respectively) (p<0.001). The median (inter-quartile range) Type 1 DM duration in antibody positive subjects was 3.3 (0.99-6.9) vs 4.9 (1.7-7.5) yr in antibody negative subjects (p=0.23). IA-2Ab prevalence decreased with disease duration > or =5 yr (19 vs 4%) (p<0.001). There was no difference in the prevalence of TgAb (25 vs 33%)(p=0.21) and TPOAb (22 vs 18%) (p=0.48) in Type 1 DM and non-diabetic subjects. Also, there was no difference in TgAb and TPOAb prevalence in antibody positive Type 1 DM (34.7%) compared to antibody negative Type 1 DM (24.4%) subjects (p=0.24). tTGAb (3/119) and TRAb (1/119) were found in low prevalence and 21-OHAb were not detected. CONCLUSIONS: Diabetes associated autoantibodies were detected in the majority of Type 1 DM subjects, suggesting a major role for autoimmunity in the pathogenesis of Type 1 DM in Sri Lankans. The prevalence of TgAb and TPOAb in Type 1 DM subjects and non-diabetic controls was relatively high and similar in both groups.

Thyroglobulin autoantibodies in iodized subjects: relationship between epitope specificities and longitudinal antibody activity.

INTRODUCTION: We previously reported a high thyroglobulin autoantibodies (TgAb) prevalence in healthy Sri Lankans after iodine supplementation. In the present study 58 TgAb-positive schoolgirls were followed up after 5 years of continued iodination. The objectives were: (1) to observe the longitudinal profile of TgAb epitope specificities and (2) to examine the relationship between these specificities and the course of thyroid autoimmunity in this population. METHODS: Paired subjects' sera (at onset and at 5-year follow-up) were tested for TgAb, thyroid peroxidase antibody (TPOAb), and TgAb epitope-specificity. Epitope reactivity was determined by employing a panel of 10 murine monoclonal antibodies (Tg-mAbs) directed against 6 Tg antigenic clusters (I-VI) in competitive enzyme-linked immunosorbent assay (ELISA) reactions with test sera. RESULTS: The overall pattern of epitope recognition in individual subject's sera remained preserved over the time period. Nine subjects showed restricted specificities while majority of the subjects were broadly heterogeneous. At follow-up, median TgAb concentration in the restricted group was higher than in the unrestricted (1650 versus 110 kIU/L; p < 0.005). Epitope specificity was a stronger determinant of TgAb persistence than the height of the initial TgAb response or the TPOAb status of subjects. CONCLUSION: Tg epitope reactivity pattern in iodised populations may identify subjects at greater risk of developing autoimmune thyroid disease (AITD).

Characteristics of a monoclonal antibody to the thyrotropin receptor that acts as a powerful thyroid-stimulating autoantibody antagonist.

Analysis of nine mouse monoclonal antibodies (mAbs) to the thyrotropin receptor (TSHR) with TSH antagonist activity showed that only one of the mAbs (RSR B2) was an effective antagonist of the human thyroid stimulating autoantibody M22. Crystals of B2 Fab were analyzed by x-ray diffraction and a crystal structure at 3.3 A resolution was obtained. The surface charge and topography of the B2 antigen binding site were markedly different from those of the thyroid-stimulating mAb M22 and these differences might contribute to the different properties of the two mAbs. B2 (but not other mouse TSHR-specific mAbs) was also an effective antagonist of thyroid stimulating autoantibody activity in 14 of 14 different sera from patients with Graves' disease. 125I-labeled B2 bound to the TSHR with high affinity (2 x 10(10) L/mol) and patient serum TSHR autoantibodies inhibited labeled B2 binding to the receptor in a similar way to inhibition of labeled TSH binding (r = 0.75; n = 20). Furthermore, labeled B2 binding was inhibited by patient serum TSHR autoantibodies with TSH antagonist activity and also by mouse and human thyroid stimulating mAbs. Overall, mAb B2 is a powerful antagonist of thyroid stimulating autoantibodies (and TSH) thus resembling closely patient serum TSH antagonist TSHR autoantibodies. Furthermore, B2 might have potentially important in vivo applications when tissues containing the TSHR (including those in the orbit) need to be made unresponsive to stimulating autoantibodies.

Sequential studies on thyroid antibodies during pregnancy.

Thyroid antibodies were measured sequentially in 25 pregnant women from a Sri Lankan population. A high prevalence of antithyroid antibodies, particularly antithyroglobulin antibodies (TgAb) had previously been demonstrated in female schoolchildren drawn from this population. In the present study TgAb were detected in 36.8% of nonpregnant controls while thyroid peroxidase antibody (TPOAb) positivity was present in 26.3%. The prevalence of both antibodies in the pregnancy study group showed a progressive decline compared to nonpregnant controls throughout gestation becoming undetectable in the third trimester. The results are consistent with an immunosuppressive effect of pregnancy in a population in whom high thyroid autoantibody titers may have resulted from a recent salt iodization program.

Isolation and characterisation of a human monoclonal autoantibody to the islet cell autoantigen IA-2.

A hybridoma secreting a human monoclonal autoantibody to the islet cell autoantigen IA-2 was prepared from peripheral lymphocytes of a patient with type 1 diabetes and Graves' disease using EBV infection followed by fusion with a mouse/human hybrid cell line. The monoclonal antibody (M13) is an IgG1/kappa and in an immunofluorescence test M13 at 1 microg/mL showed islet cell antibody reactivity equivalent to 40 JDF units. M13 IgG bound (35)S-labelled IA-2 (26% at 100 microg/mL) and (125)I-labelled IA-2 (34% at 100 microg/mL) in an immunoprecipitation assay and reacted well with IA-2 in western blotting analysis. Amino acids 777-808 in the PTP domain of IA-2 were found to be important for M13 binding in an analysis using modified (35)S-labelled IA-2 proteins. M13 V region genes were from VH1-3, D3-22, JH4b, VKI DPK8/Vd+ and JK3 genes and showed a high replacement/silent mutation ratio for both the heavy (11.0) and the light (6.0) chain genes. Mouse monoclonal antibodies (mMAbs) reactive with at least three different epitopes within IA-2 aa 604-686 corresponding to the juxtamembrane domain were also obtained. F(ab')(2) or Fab from the mMAbs inhibited serum IA-2 autoantibody binding to IA-2 in 20/22 diabetic sera whereas M13 F(ab')(2) caused inhibition in only 6/22 sera. M13 is representative of some patient serum IA-2 autoantibodies and as such provides a useful tool to study autoimmune responses to IA-2.

Screening for thyroid disease in pregnancy.

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.

Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence structure and function.

The properties of a human monoclonal antibody to the thyrotropin receptor (TSHR) (M22) with the characteristics of patient sera thyroid stimulating autoantibodies is described. Similar concentrations (pmol/L) of M22 Fab and porcine TSH had similar stimulating effects on cyclic adenosine monophosphate (cAMP) production in TSHR-transfected Chinese hamster ovary cells whereas higher doses of intact M22 immunoglobulin G (IgG) were required to cause the same level of stimulation. Patient sera containing TSHR autoantibodies with TSH antagonist (blocking) activity inhibited M22 Fab and IgG stimulation in a similar way to their ability to block TSH stimulation. Thyroid-stimulating monoclonal antibodies (TSmAbs) produced in mice inhibited 125I-TSH binding and 125I-M22 Fab binding to the TSHR but the mouse TSmAbs were less effective inhibitors than M22. These competition studies emphasized the close relationship between the binding sites on the TSHR for TSH, TSHR autoantibodies with TSH agonist activity, and TSHR autoantibodies with TSH antagonist activity. Recombinant M22 Fab could be produced in Escherichia coli and the recombinant and hybridoma produced Fabs were similarly active in terms of inhibition of TSH binding and cAMP stimulation. The crystal structure of M22 Fab was determined to 1.65 A resolution and is that of a standard Fab although the hypervariable region of the heavy chain protrudes further from the framework than the hypervariable region of the light chain. The M22 antigen binding site is rich in aromatic residues and its surface is dominated by acidic patches on one side and basic patches on the other in agreement with an important role for charge-charge interactions in the TSHR-autoantibody interaction.

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.

High leptin levels in women developing postpartum thyroiditis.

BACKGROUND: There is experimental evidence that leptin is required for the development of T helper 1 (Th1)-mediated autoimmune diseases. However, to our knowledge, there are no studies demonstrating such a role in human autoimmune thyroid disease. OBJECTIVE: In the present study we have retrospectively examined patients developing postpartum thyroiditis (PPT), as a model of autoimmune disease, for changes in serum leptin levels during the postpartum period. MATERIALS AND METHODS: The study group included 61 women in the first month postpartum who were positive for thyroid peroxidase antibodies (TPOAb+ve). Twenty TPOAb-negative (-ve), age and body mass index (BMI)-matched, postpartum women were enrolled as the control group. All subjects were evaluated for BMI, serum leptin values, thyroid function [serum free-triiodiothyronine (FT3), free-thyroxine (FT4), thyrotropin (TSH)] and autoimmunity [TPOAb levels and complement activity index (C3 index)] at 4, 12, 16, 20 and 24 weeks' postpartum. During the postpartum period, 32 of 61 TPOAb+ve women (52.4%) showed one or more episodes of thyroid dysfunction (PPTD group), whereas the remaining 29 TPOAb+ve women remained euthyroid throughout the study period (PPTE group). None of the control group developed thyroid dysfunction. RESULTS: Four weeks postpartum, TPOAb+ve women showed higher serum leptin values than TPOAb-ve women, despite comparable BMI. At this time, PPTE and PPTD patients showed no significant differences in leptin levels or leptin/BMI ratio. Throughout the postpartum period, PPTD patients maintained significantly higher leptin values and leptin/BMI ratio compared to the healthy women. In PPTE women, however, a significant reduction in leptin levels and leptin/BMI ratio was seen at 12 weeks' postpartum. This decrease was transient and correlated negatively with the variation in C3 index at the same time. No significant correlation was found between serum leptin variations and FT4 or TSH levels. CONCLUSIONS: This study has demonstrated that women developing postpartum thyroiditis have higher leptin values compared to the healthy women. The higher levels were maintained for 6 months postpartum. This result would suggest an involvement of leptin in the pathogenesis of postpartum thyroid disease, although further studies are needed to characterize the reciprocal effects of leptin, immune system and thyroid hormones during the course of this disease.

Subclinical hypothyroidism: an audit of management.

BACKGROUND: Subclinical hypothyroidism (SH) is a marker for overt hypothyroidism and vascular disease. Treatment guidelines are not universally followed. Thyroxine is recommended if serum thyroid-stimulating hormone (TSH) concentration is 10 mU/L or more, or if serum TSH is 5-9.9 mU/L (mild SH) with other risk factors, such as thyroid peroxidase antibodies (TPOAb). METHODS: We examined the management of mild SH in a retrospective case note audit of 150 consecutive subjects. Twenty-seven subjects with a serum TSH concentration above 10 mU/L were excluded from analysis. Of the group with mild SH, 27 were also excluded because of previous thyroid disease or amiodarone therapy. RESULTS: The prevalence of previous thyroid disease was similar in subjects with TSH 10 mU/L or more, compared to those with mild SH. Overall, both TPOAb and goitre status were determined in only 39% of subjects with mild SH, but in more by endocrinologists compared with general physicians (63% versus 22% for TPOAb; 47% versus 17% for goitre) (P = 0.001). Endocrinologists treated a greater number of subjects with mild SH who were eligible for thyroxine therapy compared to nonendocrine colleagues (96% versus 67%) (P = 0.024). Both groups treated subjects in whom TPOAb status was not determined (endocrinologists 21% versus general physicians 40%) (P = 0.21). CONCLUSION: In subjects with mild SH, evaluation is incomplete, a large percentage who were TPOAb positive were on appropriate therapy, thyroxine was prescribed when TPOAb status was unknown and, on the whole, endocrinologists performed better than general physicians.

Thyroglobulin epitope recognition in a post iodine-supplemented Sri Lankan population.

OBJECTIVE: 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. DESIGN: 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. RESULTS AND CONCLUSIONS: 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.