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Obstetric difficulties due to Graves' disease
  1. A Bhattacharyyaa,
  2. J D Wrightb,
  3. P A Vicea
  1. aPreston Acute Hospital NHS Trust, UK: Department of Medicine (Division of Endocrinology), bDepartment of Obstetrics
  1. Dr P A Vice, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK Patricia.Vice{at}patr.nhs.uk

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A 14 year old girl was referred to the paediatricians with symptoms of hyperthyroidism. She had a smooth diffuse goitre with dysthyroid eye disease (proptosis, lid lag, and lid retraction). Hyperthyroidism was confirmed biochemically (protein bound iodine 18.8, normal 5–8 μg). She was treated with carbimazole, 30 mg/day. Poor compliance resulted in inpatient care for treatment with carbimazole followed by subtotal thyroidectomy, two years later. Two years later she presented with a self limited episode of hyperthyroidism. Aged 22 years she was referred with eight weeks amenorrhoea when pregnancy was confirmed and terminated. She was floridly hyperthyroid (free thyroxine 36.6, normal 10–23 pmol/l, free triiodothyronine 14, normal 3–9 pmol/l; thyroid stimulating hormone (TSH) undetectable, normal 0.5–5 mU/l). She was treated with carbimazole for nine months with apparently good clinical response.

At 24 years, she was admitted in premature labour at 36 weeks, resulting in a stillborn infant (weight 1700 g, goitre of 4.4 g, and diffuse hyperplasia on histology). No obvious maternal thyroid problem had been noted during the pregnancy. Six months later an unplanned pregnancy was terminated at 10 weeks of gestation when she was proved to be hyperthyroid (free thyroxine 30 pmol/l). At 26 years, she had a first trimester spontaneous abortion. A further pregnancy at the age of 30 years without obvious thyroid disease was complicated by premature labour, resulting in an urgent caesarean section for fetal distress and a stillborn baby. This baby weighed 1870 g and a goitre was noted (thyroid weighing 6 g, diffuse hyperplasia on histology). It was when she was readmitted with wound infection that she was noted to be hyperthyroid and was referred to the Division of Endocrinology.

She was clinically and biochemically hyperthyroid (free thyroxine 23 pmol/l and free triiodothyronine 11.3 pmol/l) with dysthyroid eye disease. Her TSH receptor antibody (TSHRAb) was 95 (normal 0–10 U/l), thyroglobulin antibody (TGA) was 1: 81 920, while thyroid microsomal antibody (TMA) was 1: 1 638 400 (normal being less than 1: 400 for both TGA and TMA). The patient wished to try for a future pregnancy. After discussion, it was agreed that she would receive an ablative dose of radioactive iodine (with contraceptive care after the dose), to render her hypothyroid and maintain her on thyroxine. The plan was successful and she became hypothyroid within three months of receiving radioactive iodine. She was euthyroid on 100 μg thyroxine daily. Fifteen months after receiving radioiodine she conceived and was seen in the Department of Obstetrics by JDW. She was closely monitored throughout the pregnancy. TSH and thyroxine confirmed she remained euthyroid throughout the pregnancy. TSHRAb became undetectable in late pregnancy (table 1). Fetal monitoring confirmed an euthyroid state (no tachycardia) with normal growth and no goitre on the scan. Amniocentesis, done to assess the maturity of the fetal lungs (this is not the practice now) at 36 weeks, was complicated by antepartum haemorrhage. Emergency caesarean section resulted in a live baby (birth weight 3400 g, no goitre, normal thyroid function, and negative TSHRAb). She conceived again at 35 years, resulting in a further successful outcome (birth weight 3700 g). She was managed in the same way as the previous successful one (the TSHRAb remained in the normal range throughout the pregnancy), the baby was euthyroid, and there was no goitre. She was sterilised after the second childbirth.

Table 1

Showing the thyroid parameters, antibody status, and treatment during the first successful pregnancy

Questions

(1)
Would more aggressive monitoring of the maternal thyroid status and fetal condition in the unsuccessful pregnancies have led to a better outcome?
(2)
Is it likely that the difference in the outcome of those unsuccessful pregnancies was related to the maternal uncontrolled thyroid state or to the circulating antibody levels?
(3)
What are the three crucial factors for the successful outcome in this case?

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