Guidelines for TSH-receptor antibody measurements in pregnancy: results of an evidence-based symposium organized by the European Thyroid Association.

Abstract

Hyperthyroidism due to Graves’ disease is induced by autoantibodies stimulating the thyroid-stimulating hormone (TSH) receptor. In most patients these antibodies can be measured in serum. Graves’ disease is common in women of reproductive age, with a prevalence rate of past or present disease of 0.5‐1% (1). Classically, three therapeutic approaches are used: (i) Antithyroid drugs given for a long period, which is commonly 1‐2 years. During therapy most patients enter remission, but relapses are frequent (around 50%) after withdrawal of medication; (ii) Radioiodine therapy. This may initially aggravate the autoimmune reaction, but most patients become euthyroid or hypothyroid, due to the reduction in thyroid follicular cell mass; (iii) Subtotal or near total thyroidectomy. Pregnancy is commonly accompanied bya fall in thyroid autoimmune activity, and women with Graves’ disease may spontaneously enter remission during pregnancy. However, disease activity persists in some pregnant patients, and occasionally onset of Graves’ disease is seen. The recommended therapy for Graves’ disease during pregnancy is monotherapy with antithyroid drugs (propylthiouracil, methimazol or carbimazol). While thyroid hormones produced by or given to the mother cross the placenta in only limited amounts, both TSH-receptor stimulating antibodies and antithyroid drugs readily cross the placenta and affect fetal thyroid function. Ideally, a balance between stimulating antibodies and drugs which keeps the mother euthyroid will also maintain euthyroidism in the fetus. Fortunately this is close to reality; during therapy with antithyroid drugs the thyroid state of the fetus parallels that of the mother, but with a tendency to be slightly lower (2). Hence, a pregnant woman with Graves’ disease and an intact thyroid should receive the minimal dose of antithyroid drugs which keeps her thyroid function near the upper end of normality. After delivery, antithyroid drugs are cleared from the neonatal circulation within the first days, whereas TSH-receptor antibodies disappear much more slowly and may stimulate the thyroid during the first weeks or even months of life. Delayed neonatal hyperthyroidism may therefore develop, constituting a potentially life-threatening medical condition. The situation is different when a pregnant woman has previously been treated for Graves’ hyperthyroidism with radioiodine or surgery, and especially when she is receiving thyroxine substitution therapy. In this situation, the thyroid function of the mother does not reflect thyroid function in the fetus. If the mother still produces large amounts of TSH-receptor stimulating antibodies, fetal hyperthyroidism may develop. Also, neonatal hyperthyroidism may be present at birth and last for months if left untreated. Occasionally antibodies against the TSH receptor will bind to the receptor without stimulation, but rather will block the normal effect of TSH. This may cause hypothyroidism in the mother and the fetus, and transiently in the newborn. This rare variant, which has been detected in 1 in 180 000 newborns in North America (3), is not discussed in detail.