Thyroid autoantibody profiles in ophthalmic dominant and thyroid dominant Graves' disease differ and suggest ophthalmopathy is a multiantigenic disease.

BACKGROUND: Thyroid-associated ophthalmopathy (TAO) occurs in 25-50% of patients with Graves' disease (GD) and is occasionally seen in hypothyroid Hashimoto's disease or euthyroid individuals. The link between TAO and hyperthyroidism remains unclear. We hypothesized that qualitative or quantitative differences in thyroid antibodies might determine individual predisposition to these features. METHODS: In a prospective study over 3 years, thyroid antibody levels were measured in all patients diagnosed at the Singapore National Eye Centre to have GD. These patients had no known history of thyroid disease, presented with eye complaints and diagnosis was made by an ophthalmologist. A total of 31 patients were identified. Antibody levels were compared against 71 consecutive patients referred to a thyroid clinic (TC) for thyrotoxic symptoms in whom the diagnosis of GD was confirmed by a thyroidologist. FINDINGS: Thyroid autoantibody profiles of patients diagnosed at the ophthalmology centre (OC) and TC differed markedly. OC patients had significantly higher TSI (P = 0.003) but lower TPOAb (P = 0.008) and TgAb levels (P < 0.001). In contrast, TC patients had higher free T4 (P = 0.048) and higher TBII levels (P < 0.001). Antibody levels were correlated with four parameters of ophthalmopathy--chronic lid retraction, lid swelling, proptosis and extraocular myopathy (EOM). On univariate logistic regression analysis, TSI was a positive predictor and TPOAb and TgAb negative predictors of all four features. In the absence of TgAb, the odds ratios for individual TAO features ranged from 2.8 to 7.9, with corresponding values of 3.9-10.2 when TPOAb was absent. In stepwise logistic regression analysis, TSI was the strongest independent predictor of all aspects studied: lid fullness P = 0.001, proptosis P = 0.001, lid retraction P = 0.008, EOM P = 0.009. Among smokers, TPOAb were significantly lower (P = 0.044) but no association between smoking and the other antibodies was observed. INTERPRETATION: The study demonstrates markedly different thyroid autoantibody profiles in newly diagnosed GD patients with ophthalmic dominant as opposed to thyroid dominant features. It suggests differing antibody patterns are associated with predisposition to hyperthyroidism and orbitopathy. In addition, an association between smoking and low TPOAb levels was noted.

Thyroid diseases in pregnancy.

INTRODUCTION: Changes in thyroid function in pregnancy encompass both hyper- and hypothyroidism. Failure to maintain euthyroidism may place both mother and foetus at higher risk of adverse obstetrical outcomes. This review examines the differences between physiological and pathological thyroid dysfunction during pregnancy and their management. METHODS: Data were obtained from relevant clinical studies and review articles listed in MEDLINE. Additional cross-references from selected articles were identified. RESULTS: In hyperthyroidism, the challenge lies in differentiating gestational transient thyrotoxicosis (GTT) from actual pathological states during the first trimester. GTT is thought to be due to elevation of isoforms of human chorionic gonadotropin (hCG) which may exert potent thyrotrophic effects. While thionamides are safe, the lowest possible dose should be used together with close monitoring of maternal thyroid function in order to avoid over-treatment. Surgery for thyroid nodules may be safely performed during the second trimester. Conversely, diagnosing hypothyroid states, particularly subclinical hypothyroidism and postpartum thyroiditis (PPT), require a high index of suspicion. High levels of thyroid peroxidase antibodies (TPOAb) and thyroid stimulating hormone (TSH) in early pregnancy may be predictive of PPT and subsequent permanent hypothyroidism. Clinicians must recognise the need to increase thyroxine replacement as maternal hypothyroidism may adversely affect the IQ scores of children. The association between thyroid autoimmunity and recurrent abortions remain unclear. CONCLUSION: Regardless of the aetiology of thyroid dysfunction, the key to management lies in individualized therapy in close collaboration with the obstetrician.