Best Practice & Research Clinical Endocrinology & Metabolism
10Hyperthyroidism in pregnancy
Section snippets
Prevalence
Textbooks on the thyroid and endocrine system define thyrotoxicosis as the clinical syndrome caused by the circulation of excessive thyroid hormones. Hyperthyroidism is defined when excessive thyroid hormone production is due to thyroid gland overactivity. The vast majority of cases of excessive serum thyroid hormone concentration seen in pregnancy are due to the overproduction of thyroid hormones (Graves' disease, toxic nodular goiter); in the postpartum period, thyrotoxicosis may be due to
Historical review
Prior to the introduction of thiouracil drugs for the treatment of hyperthyroidism in the late 1940s and early 1950s, several publications reported the outcome of pregnancy in women affected by hyperthyroidism. Gardiner-Hill15 reported in 1929, that supportive therapy throughout pregnancy resulted in a fetal loss of 45%, without maternal losses. When patients were prepared with potassium iodine prior to subtotal thyroidectomy, the perinatal mortality was 4%.16 Although therapeutic abortion was
Clinical presentation and course
In pregnancy, the natural course of Graves' hyperthyroidism is characterized by an exacerbation of symptoms in the first trimester and during the postpartum period with an amelioration of them in the second half of pregnancy. Placental hCG stimulation of the thyroid gland in the first trimester has been suggested as the cause of this exacerbation4; immunological responses caused by changes in lymphocyte subsets could explain spontaneous improvement in the second half of pregnancy and
Symptoms and signs
The classical symptoms of hyperthyroidism are shown in Table 4. In most patients the onset of the disease is gradual and several months pass until the patients present to the physician; in some patients, however, symptoms may be of short duration, triggered by acute stress; it is not uncommon for the disease to occur after a death in the family, an accident, or other stressful situations. The most common symptoms at presentation in young women are irritability, palpitations, nervousness,
Laboratory tests
Free thyroxine determination or calculation of the free thyroxine index (FT4I) (using total thyroxine levels and a test for assessing thyroxine binding globulin, such as resin uptake) are routine tests in most clinical laboratories, with the result available in 24–48 h. Almost every patient with Graves' disease has elevated free T4 or FT4I concentrations. A suppressed TSH value in the presence of a high free T4 or FT4I confirms the diagnosis of hyperthyroidism.34 It must be kept in mind,
Maternal and perinatal complications
Significant maternal and perinatal morbidity and mortality were reported in early studies of pregnancy complicated by hyperthyroidism, at the time when iodine therapy with or without thyroidectomy was the only therapeutic tool.16., 17., 37. The incidence of toxemia in several series was close to 70% and perinatal mortality was around 7%; the incidence of spontaneous abortion was also high. In the last 30 years, however, there has been a significant decrease in the incidence of maternal and
Management
Treatment of hyperthyroidism is essential to prevent maternal, fetal and neonatal complications. The goal of treatment is normalization of FT4 or FT4I as soon as possible and to maintain euthyroidism with the minimum amount of antithyroid medication. Because antithyroid drugs cross the placenta, excessive antithyroid medication may affect fetal thyroid function, with the development of hypothyroidism with or without goiter. Patients should be monitored at regular intervals and the dose of
Thyroid storm
Thyrotoxic crisis or accelerated hyperthyroidism is an uncommon but serious complications of hyperthyroidism. It is an acute event, occurring in patients with untreated or poorly controlled disease, it is precipitated by infection, trauma, surgery, diabetic ketoacidosis71., 72. and in pregnancy by toxemia, placenta previa and induction of labor.29 The incidence in pregnancy has been reported to be between 1 and 2%. Davis et al29 collected from the literature seven cases from 34 untreated women,
Neonatal hypothyroidism induced by maternal ingestion of ATD
It has been estimated that 25% of cases of transient neonatal hypothyroidism were due to maternal ingestion of ATD.73 Early reports soon after ATD was introduced in the management of hyperthyroidism in pregnancy showed a significant percentage of neonatal goiter and even cretinism. It was thought that large doses of PTU were the causative factor, and it was recommended to decrease the dosage with progression of pregnancy and clinical improvement of the symptoms.74 Cheron et al58 suggested that,
Neonatal hyperthyroidism
Neonatal hyperthyroidism is infrequent with an incidence of less than 1% of infants born to mothers with Graves' disease, therefore affecting one neonate out of 50 000. In the vast majority of cases, the disease is caused by the transfer of maternal immunoglubulin antibodies to the fetus. These stimulating thyroid antibodies to the TSH receptor (thyroid stimulating antibodies [TSI]), when present in high concentrations in maternal serum, crossing the placental barrier, stimulate the fetal
Neonatal central hypothyroidism
There are several reported cases of neonatal central hypothyroidism in infants born of mothers with Graves' disease whose hyperthyroidism was not controlled during pregnancy.79., 80. The hypothesis is based on the fact that high levels of serum thyroxine in the maternal circulation, crossing the placenta barrier, feedback to the fetus pituitary with suppression of fetal pituitary TSH. In most cases, the diagnosis is made at birth or a few days after delivery. Neonatal serum FT4 is low and serum
Fetal hyperthyroidism
In mothers with a history of Graves' disease, previously treated with ablation therapy, either surgery or 131I, concentrations of TSI may remain elevated, in spite of maternal euthyroidism.81., 82. Heckel et al82 reviewed nine cases of fetal hyperthyroidism; fetal tachycardia was the most frequent sign, whereas olygohydramnios and IUGR were reported in only two cases; fetal goiter was detected by ultrasonography in three cases. Although bone maturation is accelerated, it is not very accurately
Postpartum care
Following delivery, ATD therapy is continued and mothers are advised about breastfeeding (see below). In those patients in whom ATD therapy was discontinued during pregnancy, they should contact their physician if hypermetabolic symptoms return, in which case a determination by thyroid tests is indicated. In asymptomatic patients, routine determination of TSH and FT4 or FT4I is performed at about 6 weeks postpartum. Since recurrences of hyperthyroidism are not unusual in the few months after
Breastfeeding
Breast-feeding should be permitted if the daily dose of PTU is less than 150–200 mg/day or methimazole 10 mg/day. It is prudent to give the total dose in divided doses after each feeding; the infant should be given a follow-up thyroid test.56., 86. In a very provocative paper, PTU was given to lactate hyperthyroid mothers whose infants were born with elevated serum TSH levels; infants serum TSH normalized even with continuation of PTU therapy by the mothers.87 In another study, thyroid tests
Summary
The differential diagnosis of hyperthyroidism early in pregnancy represents a challenge for the physician. In the first trimester of pregnancy, gestational thyrotoxicosis is the most common hyperthyroid abnormality; it is a transient condition that requires no antithyroid therapy. In the majority cases of Graves' hyperthyroidism, the symptoms antedate pregnancy for many weeks or months; a careful medical history and examination is able to differentiate both entities. For hyperthyroidism due to
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2016, Annales d'EndocrinologieCitation Excerpt :GD during pregnancy involves risks to the mother, foetus and neonate that are related to both the disease itself and its treatment. Maternal hyperthyroidism can be complicated by cardiac insufficiency, thyrotoxicosis and pre-eclampsia [2,4]. The transplacental passage of TSH receptor antibodies (TRAb) can cause goitre and foetal and/or neonatal hyperthyroidism.
Thyroid Storm in Pregnancy: A Rare Case Report
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