Obstetric controversies in thyroidology.

It is well known that thyroid disorders commonly affect women. The care of pregnant women affected by thyroid disease is an important clinical challenge for endocrinologists. Hypothyroidism is the commonest problem, and maternal hypothyroxinemia has been linked to adverse feto-maternal outcomes. This article would discuss the controversy regarding first-trimester thyroid hormone deficiency and fetal brain development. Certain obstetric controversies in the management of hyperthyroidism in pregnancy, including the indications of TSH receptor antibody measurements and fetal thyroid status monitoring would also be discussed.

INTRODUCTION

Thyroid disease, especially hypothyroidism, is very common in India, especially in women.[1234] Hypothyroidism is commoner in women than men. Positivity to thyroid antibodies is also common in the general population, particularly in women. This article on obstetric controversies in thyroidology will focus on hypothyroidism and autoimmune disease. Being part of a mini-review series, this article will not provide an extensive review of the subject, but would rather cover selected controversies of interest to the practicing endocrinologist.

UNDERSTANDING RISK IN MATERNAL HYPOTHYROXINEMIA

In general, studies have suggested that early maternal hypothyroxinemia affects the offspring subject, as the fetal brain development occurs in the first trimester, and because fetal thyroid gland develops after the 12th week. This has often put clinicians in a quandary, as patients often present with pregnancy and very high TSH values, and gynecologists are often considering termination of pregnancy in view of hypothyroidism. As there are no Indian studies correlating maternal hypothyroxinemia and fetal risk, we must continue to rely on international data. From these, international research papers, it is well known that - (a) untreated hypothyroidism in pregnancy may lead to lowered intelligence quotient in the offspring (b) children born to mothers with untreated hypothyroidism had higher learning disabilities and (c) iodine deficiency in pregnancy can also lead to neuropsychological problems in offspring.[56] Iodine deficiency in Indian women has been variably reported as low or high.[7]

IS MEDICAL TERMINATION OF PREGNANCY (MTP) JUSTIFIED IN MATERNAL HYPOTHYROIDISM?

In order to understand this, it is important to analyze the MTP act of 1971.[8] According to this act, MTP can be advised up to 12 weeks, and the decision can be made by one qualified doctor. In case two qualified doctors can concur, MTP can be done up to 20 weeks. From the list of qualifications to be categorized as a doctor qualified to advise or perform MTP, it is clear that being an endocrinologist does not qualify a doctor as far as MTP is concerned. MTP is generally performed to save the life of the mother, for social indications and for what is termed “eugenic” reasons. Eugenic indications are when there is a substantial potential of a baby being born with serious mental or physical disability. These reasons include-anencephaly, chromosomal disorders Down's syndrome, genetic diseases like hemophilia and exposure to teratogens, radiation, and rubella. The term hypothyroidism is not listed.

Obviously, it is better to discuss the current state of evidence with the patient. However, some generalizations come to mind-if the pregnancy is more than 20 weeks, there is no doubt that MTP should not be done. Similarly, in cases of subclinical hypothyroidism too, there is no indication for MTP.[9] In ‘severe’ cases of hypothyroidism where the conception has occurred without difficulty-the benefits and risks may be discussed with the patient-and unless there is a request from the patient, MTP cannot be recommended for hypothyroidism. In the management of hypothyroidism in pregnancy it may be remembered that the baby's intelligence quotient is not the sole overriding consideration and that there are other problems that can be a consequence of hypothyroidism in pregnancy. This includes miscarriages, pre-eclampsia, anemia, abruptio placentae, and postpartum hemorrhage.[1011]

HYPERTHYROIDISM IN PREGNANCY AND AREAS OF CONTROVERSY

This article will assume that readers are familiar with the following aspects of managing hyperthyroidism in pregnancy-the need to treat with the minimum dose of anti-thyroid drugs to keep the TSH normal and the FT4 in the upper half of the normal range, the need to monitor maternal and fetal health and the current guidelines that suggest the use of propylthiouracil in the first trimester and carbimazole/methimazole in the rest of pregnancy, as well as the trimester specific TSH cutoffs in pregnancy. One area of ambiguity is the need for a recommendation on TSH-receptor antibody testing in pregnancy. Recently, a review has suggested that international consensuses are concordant about the indications for TSH-receptor (TSHR) antibodies in pregnancy.[121314] In a pregnant patient on anti-thyroid drugs, known to have Graves’ disease, TSHR antibodies must be measured during the 22nd week. In pregnant women with a past history of Graves’ disease treated with radio-iodine or surgery-TSHR must be measured at about 22-28 weeks. Finally, TSHR may also be measured in mothers with a previous history of TSHR antibody positivity, and also in mothers with previous history of neonates born with neonatal thyrotoxicosis. Is there a need for fetal monitoring in thyrotoxicosis, and if so, what are the fetal ultrasound criteria to be used? This has long been unclear and present guidelines have attempted to shed light on this clinically relevant issue. Fetal ultrasound should look for fetal heart rate and fetal goiter both signaling that the anti-thyroid drugs may have crossed the placenta and also for signals of hyperthyroidism like fetal tachycardia, intrauterine growth retardation, and features like advancing bone age as well as fetal hydrops. It is best that fetal ultrasounds be done when the TSHR antibodies are more than 2-3 folds higher than normal, and from the 18th to the 22nd week of gestation. After fetal surveillance is begun, the TSHR antibodies may need to be tested every 6 weeks or so. In the preceding lines, the article has looked at what happens if TSHR antibodies and anti-thyroid drugs cross placenta. A third possibility is that of thyroxine crossing the placenta: This happens in cases of severe, long-standing thyrotoxicosis. This may suppress the pituitary of the fetus and thus, after birth the suppressed pituitary may take a while to recover-resulting in a period of transient-central hypothyroidism. This suggests that babies of hyperthyroid mothers need to be screened with TSH and Free T4 estimations. A final issue in question has been the use of anti-thyroid drugs in lactation. This has been recently settled, with studies showing that neither methimazole 30 mg/day nor propylthouracil 300 mg per day has any detrimental effect on the breast-feeding neonate's thyroid function. However, the drug of choice is methimazole/carbimazole-so that the liver of the baby as well as the mother may be protected from liver necrosis attributable to propylthiouracil.

FUTURE DIRECTIONS

In general, the thyroid gland has not received the importance that it deserves-the diseases being so common and widespread.[1516] Other than hyperthyroidism and hypothyroidism, other thyroid diseases also require study such as for instance thyroid nodules. Clinicians are also aware of the occurrence of thyroid nodules that enlarge in pregnancy; if the lesion is suspicious for malignancy, thyroidectomy may be considered in the 2nd trimester, but if diagnosed later then surgery may be done after delivery and suppressive thyroxin treatment instituted.[1718] A third obstetric controversy is the hyperthyroidism and treatment during pregnancy as well as lactation. Further research is required to establish answers to some of the controversies in the management of thyroid disease in pregnancy.