thyroid disease in pregnancy د.نادية مضر الحلي
maternal physiology:
thyroid disease is the commonest pre-existing endocrine disorder in pregnant women. thyroid-stimulating hormone (tsh) is released from the anterior pituitary. it increases both the synthesis and release of thyroxin (t4) and triiodothyronine (t3). the t3 and t4 are mostly bounded to thyroid binding globulin. the unbound thyroid hormones have biological activity only 0.04 % of t4 and 0.05 % of t3 are free.
iodide is essential for the synthesis of thyroid hormones, and the thyroid gland actively traps iodine & produce t4. circulating t3 is produced principally by peripheral deiodination of t4.
in pregnancy, there is increased tbg production as a result of increased oestrogen synthesis. this leads to an increase in the serum concentrations of total t4 and t3, but not the free circulating thyroid hormones.
there is iodine deficiency in pregnancy as a result of loss through increased glomerular filtration. this results in increased uptake by the thyroid gland, which results in enlargement and the appearance of a goitre. fetal thyroid activity also depletes the maternal iodide pool from the second trimester.
as human chorionic gonadotrophin (hcg) and tsh share a common alpha subunit and have similar beta subunits, tsh receptors are prone to stimulation by hcg.
fetal thyroid function
during the first trimester, the fetus requires thyroxin for normal fetal brain development. from 10 weeks gestation, the fetal thyroid gland produces both t4 and t3 and there is little relationship between maternal and fetal levels. fetal levels reach those of the adult at 16 weeks gestation.
congenital hyperthyroidism can occur through tsh receptor stimulating antibodies which cross the placenta.
iodine deficiency:
women in areas of iodine deficiency may have goitres and reduced reproductive success. in iodine deficiency, the maternal thyroid gland has a greater affinity for iodide than the placenta and the fetuses are thus prone to cretinism, the leading preventable cause of mental retardation worldwide. the fetal cochlea, cerebral neocortex and basal ganglia are particularly sensitive to iodine deficiency. iodine administration prior to conception and up to the 2nd trimester will improve neurological outcome by protecting the fetal brain. lodination of water, salt or flour can easily achieve this.
hyperthyroidism
hyperthyroidism is usually due to graves disease (autoimmune thyrotoxicosis). less than 5 % of cases result from a toxic nodule, thyroiditis or a carcinoma.
graves disease is associated with a hyperplastic goitre and often with exophthalmos. disease severity is correlated to immunoglobulin g (igg) thyrotropin receptor stimulating antibody levels. in first trimester, the disease may be exacerbated by high hcg levels.
typical signs of hyperthyroidism are difficult to elicit in preg
nancy. symptoms, such as fatigue and heat intolerance, are common in pregnancy.
it is essential to maintain euthyroidism in pregnancy, as uncontrolled disease is associated with maternal and fetal complications, including thyroid storm, heart failure and maternal hypertension, increased rates of premature labour, growth restriction and stillbirth.
treatment is similar to that for non-pregnant women, although radioactive iodine must not be given. surgery may be considered if medical treatment fails or there is a clinical_suspicion of cancer or compressive symptoms due to a goitre.
medical treatment involves blocking thyroid hormone synthesis. propylthiouracil (ptu) or carbimazole both reduce the titre of tsh receptor antibodies, directly influencing the aetiology of graves disease. both drugs cross the placenta in the same proportion & are equally beneficial and the dose of either can be titrated against maternal well-being and biochemical status. neither ptu nor carbimazole is thought to be teratogenic.
antithyroid drugs can cause agranulocytosis and so a sore throat should be thoroughly investigated.
it is recommended that thyroid function tests be performed every 4-6 weeks. when graves disease is stable, beta-blockers (propranolol ) can be used to control the symptoms of tachycardia or tremor.
as both ptu and carbimazole cross the placenta, both may influence the fetus. the minimal dose required in the mother should therefore be used, and it is usual to aim for free t4 levels at the upper limit of normal.
fetal hyperthyroidism
when maternal thyrotropin receptor stimulating antibodies cross the placenta, they can cause fetal or neonatal thyrotoxicosis. the fetal thyroid is capable of responding to these antibodies after 20 weeks gestation. assessment should include maternal perception of fetal movements and measurement of the fetal heart rate, which, if > 160 bpm may be indicative of fetal thyrotoxicosis. an ultrasound scan used to exclude a fetal goitre or fetal growth restriction.
complications include premature delivery, hydropingings fetalis and death can occur and a fetal goitre can cause polyhydramnios and an obstructed delivery. the condition is also associated with craniosynostosis and, intellectual impairment.
the fetus can be effectively treated by maternal administration of antithyroid agents, which cross the placenta. the fetal heart rate can be used to titrate the dose of antithyroid drugs.
hypothyroidism in pregnancy:
hypothyroidism occurs in nearly 1 per cent of pregnant women and is usually due to autoimmune hashimoto s thyroiditis or idiopathic myxoedema the condition can also occur following treatment of hyperthyroidism.
there is a reduced intelligence quotient (iq) in babies of women with hypothyroidism that is not adequately treated, or that goes unrecognized. the insult is likely to occur in the first trimester, and therefore pre-conceptual optimization of t4 therapy is important.
as hypothyroidism is associated with subfertility, it is rare to make a new diagnosis in pregnancy. the classical symptoms of hypothyroidism such as tiredness, constipation, anaemia, weight gain, carpal tunnel syndrome and hair changes are common in pregnancy and cannot be relied upon to discriminate onset or worsening of the disease. the management is therefore based principally on biochemical measures. thyroxine is titrated against biochemical results and is safe in pregnancy and lactation. as long as the patient is clinically euthyroid, thyroid_function test should be performed every 2-3 months.
postpartum thyroiditis:
postpartum thyroiditis occur up to a year following delivery and can_manifest as high or low t4 levels. most women will not have clinically apparent disease, or present with depression or be diagnosed as having hashimoto s hypothyroidism.
the condition is thought to be autoimmune and presents postpartum following a return to normal immunity after delivery. histology from thyroid biopsies suggests a chronic thyroiditis with lymphocytic infiltration.
the disease may present initially between 1 and 3 months postpartum with thyrotoxicosis and later with hypothyroidism. if symptomatic with hyperthyoidism beta-blockers can be used antithyroid drugs are inappropriate as t4 production is not increased. hyperthyroidism is due to destruction of thyroid follicles & release of preformed hormones. the destruction of thyroid follicles ultimately leads to hypothyroid phase. a course of t4 may be necessary.
the period of hypothyroid state is variable, and permanent hypothyroidism can result. the condition will recur in 70 per cent of future pregnancies and women with postpartum thyroiditis should be followed up to ensure that permanent hypothyroidism does not occur.