Guidelines For TSH-receptor Antibody Measurements in Pregnancy: Results of An Evidence-Based Symposium Organized by The European Thyroid Association
Guidelines For TSH-receptor Antibody Measurements in Pregnancy: Results of An Evidence-Based Symposium Organized by The European Thyroid Association
Guidelines For TSH-receptor Antibody Measurements in Pregnancy: Results of An Evidence-Based Symposium Organized by The European Thyroid Association
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Hyperthyroidism due to Graves’ disease is induced by The situation is different when a pregnant woman
autoantibodies stimulating the thyroid-stimulating hor- has previously been treated for Graves’ hyperthyroidism
mone (TSH) receptor. In most patients these antibodies with radioiodine or surgery, and especially when she
can be measured in serum. Graves’ disease is common is receiving thyroxine substitution therapy. In this
in women of reproductive age, with a prevalence rate of situation, the thyroid function of the mother does not
past or present disease of 0.5–1% (1). Classically, three reflect thyroid function in the fetus. If the mother still
therapeutic approaches are used: (i) Antithyroid drugs produces large amounts of TSH-receptor stimulating
given for a long period, which is commonly 1–2 years. antibodies, fetal hyperthyroidism may develop. Also,
During therapy most patients enter remission, but neonatal hyperthyroidism may be present at birth and
relapses are frequent (around 50%) after withdrawal of last for months if left untreated.
medication; (ii) Radioiodine therapy. This may initially Occasionally antibodies against the TSH receptor will
aggravate the autoimmune reaction, but most patients bind to the receptor without stimulation, but rather will
become euthyroid or hypothyroid, due to the reduction block the normal effect of TSH. This may cause
in thyroid follicular cell mass; (iii) Subtotal or near total hypothyroidism in the mother and the fetus, and
thyroidectomy. transiently in the newborn. This rare variant, which
Pregnancy iscommonlyaccompanied bya fallinthyroid has been detected in 1 in 180 000 newborns in North
autoimmune activity, and women with Graves’ disease America (3), is not discussed in detail.
may spontaneously enter remission during pregnancy.
However, disease activity persists in some pregnant
patients, and occasionally onset of Graves’ disease is seen.
Methods
The recommended therapy for Graves’ disease during The clinical value of measuring TSH-receptor antibodies
pregnancy is monotherapy with antithyroid drugs in pregnant women to predict neonatal hyperthyroidism
(propylthiouracil, methimazol or carbimazol). has been examined in several studies. To evaluate the
While thyroid hormones produced by or given to the evidence for recommending such measurements, the
mother cross the placenta in only limited amounts, both European Thyroid Association initiated a symposium in
TSH-receptor stimulating antibodies and antithyroid September 1997 at its meeting in Munich. All reports on
drugs readily cross the placenta and affect fetal thyroid the subject containing original data were identified by a
function. Ideally, a balance between stimulating anti- systematic reference search (29 articles). They were
bodies and drugs which keeps the mother euthyroid will thoroughly read by the present authors. Among them 11
also maintain euthyroidism in the fetus. Fortunately articles fulfilled the following criteria: a systematic
this is close to reality; during therapy with antithyroid investigation of more than 12 pregnant women with
drugs the thyroid state of the fetus parallels that of the Graves’ disease including evaluation of neonatal thyroid
mother, but with a tendency to be slightly lower (2). function and measurements of TSH-receptor antibodies.
Hence, a pregnant woman with Graves’ disease and an They also included data on more than one case of
intact thyroid should receive the minimal dose of neonatal hyperthyroidism. Two of the articles more
antithyroid drugs which keeps her thyroid function or less described patients also published in another
near the upper end of normality. article. Hence, nine reports were finally selected for
After delivery, antithyroid drugs are cleared from detailed evaluation and discussion during the sympo-
the neonatal circulation within the first days, whereas sium. A total of 454 pregnant women (462 pregnancies)
TSH-receptor antibodies disappear much more slowly and with Graves’ disease (range 14–107 women in individual
may stimulate the thyroid during the first weeks or even papers) and their 466 newborns were described. There
months of life. Delayed neonatal hyperthyroidism may were three reports from Europe (4–6), three from Japan
therefore develop, constitutinga potentially life-threatening (7–9), two from the USA (10, 11) and one from Australia
medical condition. (12).
8 Matsuura N, Fujieda K, Iida Y, Fujimoto S, Konishi J, Kasagi K et al. 12 Mortimer RH, Tyack SA, Galligan JP, Perry-Keene DA & Tan YM.
TSH-receptor antibodies in mothers with Graves’ disease and Graves’ disease in pregnancy: TSH receptor binding inhibiting
outcome in their offspring. Lancet 1988 i 14–17. immunoglobulins and maternal and neonatal thyroid function.
9 Tamaki H, Amino N, Aozasa M, Mori M, Iwatani Y, Tachi J et al. Clinical Endocrinology 1990 32 141–152.
Universal predictive criteria for neonatal overt thyrotoxicosis 13 Fuhrer D, Wonerow P, Willgerodt H & Paschke R. Identification of
requiring treatment. American Journal of Perinatology 1988 5 a new thyrotropin receptor germline mutation (Leu629Phe) in a
152–158. family with neonatal onset of autosomal dominant nonauto-
10 Zakarija M & McKenzie JM. Pregnancy-associated changes in the immune hyper-thyroidism. Journal of Clinical Endocrinology and
thyroid-stimulating antibody of Graves’ disease and the relation- Metabolism 1997 82 4234–4238.
ship to neonatal hyperthyroidism. Journal of Clinical Endocrinology
and Metabolism 1983 57 1036–1040.
11 Skuza KA, Sills IN, Stene M & Rapaport R. Prediction of neonatal
hyperthyroidism in infants born to mothers with Graves disease. Received 15 September 1998
Journal of Pediatrics 1996 128 264–268. Accepted 29 September 1998