A number of predictable changes occur in the thyroid gland during pregnancy that has consequences for those evaluating and managing pregnant patients.

The thyroid gland normally enlarges as much as 18% in volume, a change that can be measured sonographically, and occasionally detected clinically. A more significant change may reflect an underlying abnormality.

Inadequate amounts of iodine intake can lead to a maternal goiter. There is both increased renal clearance of iodine and increased fetal uptake of iodine can lead to maternal goiter if maternal iodine intake does not match these losses.

Thyroid nodules occur with the same frequency during pregnancy as in non-pregnancy, and are evaluated with fine needle aspiration. In the event a thyroid cancer is found, surgery is generally postponed, without penalty, until after delivery, to reduce surgical complications.

Human chorionic gonadotropin, or HCG, has a mild, direct stimulatory effect on thyroid hormone production.

During the first trimester, as maternal HCG levels rise, maternal free T4 and T3 levels also rise. This elevation usually remains at the upper limit of normal, but is accompanied by a reactive drop in TSH.

Whenever HCG levels are unusually elevated, for example with multiple gestations, hyperemesis gravidarum, or gestational trophoblastic disease, these changes in thyroid indices can be even more dramatic. In such cases, the patient may develop a transient and usually subclinical hyperthyroidism that occasionally causes some mild symptoms.

Estrogen, produced in large quantities during pregnancy, leads to a significant increase in TBG because of increased production and decreased clearance. This increased TBG binds more thyroxine and triiodothyronine.

Consequently, if a pregnant woman’s total T4 or total T3 is measured, they often will both be elevated, reflecting this increase in bound hormone. But even though the total T4 and T3 are elevated, the free, unbound T4 and T3 will be normal.

So, considering the HCG and estrogen changes, if a pregnant woman in her first trimester were to be evaluated for thyroid hormone levels, it would not be surprising to find elevated total T4 and T3, and a modestly depressed TSH. Someone who doesn’t understand these normal pregnancy changes might be tempted to conclude that this woman is hyperthyroid, but that person would likely be wrong. If they were to test her free T4 and T3, they would find normal values in this symptom-free patient.

That’s not to say that hyperthyroidism does not exist in early pregnancy. To the contrary, uncontrolled or poorly controlled hyperthyroidism is associated with a number of adverse pregnancy outcomes, including:

• Spontaneous abortion
• Stillbirth
• Preterm labor
• Low birth weight
• Pre-eclampsia
• Maternal heart failure

The most common cause of overt hyperthyroidism during pregnancy is Grave’s disease, although there can certainly be other causes.

Because of the normally elevated total T4 and T3, and the normal modest suppression of TSH during pregnancy, the diagnosis of hyperthyroidism hinges on the elevation of Free T4 and T3, accompanied by a TSH level < 0.01 mU/L.

Beta blockers, thionamides, and surgery can be used to treat hyperthyroidism during pregnancy, but there are complexities regarding the optimum gestational age and duration of use. Radioactive iodine therapy is not used during pregnancy as it crosses the placenta and concentrates in the fetal thyroid gland.

Pregnancies complicated by hyperthyroidism require close monitoring of the fetus for evidence of thyrotoxicosis, cardiac and growth problems. Thyroid hormone does cross the placenta, but only to a limited extent. Same with TSH. But TSH-receptor antibodies do cross the placenta in clinically significant amounts and can lead to fetal hyperthyroidism, with tachycardia, cardiac failure, fetal hydrops, fetal goiter and poor growth.

Hypothyroidism may also complicate pregnancy and also carries significant risks, among them:

• Preterm delivery
• Pre-eclampsia
• Perinatal morbidity and mortality
• Cognitive impairment
• Placental abruption

But there are two mitigating factors to the problem of hypothyroidism during pregnancy. The more severe forms of hypothyroidism are the ones more often associated with these adverse outcomes, but those are also the women least likely to get to the point in pregnancy where these issues can arise, because of anovulation and infertility, and also the increased miscarriage rates found among these patients with the more severe forms of the disease.

Because of the normal lowering of TSH during pregnancy, the diagnosis of hypothyroidism is based on a TSH > 2.5, at least during the first trimester. Screening for this condition is controversial, with some physicians recommending universal screening in the first trimester, and others recommending testing only of those symptomatic or at high risk.

Treatment involves aggressive use of thyroid hormone, sufficient to make the patient euthyroid, with TSH levels less than 2.5 and greater then 0.1. Because it may take weeks for full equilibration to occur, followup TSH levels are monitored 4 weeks after any change in dosage, and many physicians will follow TSH at 4 week intervals throughout the pregnancy.

For women with pre-existing hypothyroidism who are already on a stable dose of thyroid hormone, their dosage needs can be expected to increase up to 50% during pregnancy. Because it is important to avoid low thyroid levels at any time during pregnancy, many physicians will increase the pre-pregnancy thyroid hormone dose by 30% at the first prenatal visit, and then follow the 4-week TSH levels, making additional adjustments as needed to keep the TSH between 0.1 and 2.5.

Postpartum, up to 10% of women will experience a transient thyroiditis, and up to 25% among those with type 1 diabetes. During the hyperthyroid phase, beta blockers may be needed to control symptoms. During the hypothyroid phase, thyroxine may be needed, and is usually continued for 6 months before tapering to determine if the hypothyroid status will be permanent, or has resolved.