Thyroid disease is a common endocrinopathy found in 1% of women of reproductive age. Thyroid Stimulating Hormone(TSH) controls the thyroid gland by inducing the transport of iodine into the gland, and then the subsequent secretion of thyroxine (T4) and Triiodothyronine (T3) into circulation. T3 is the most active metabolite, followed by T4 and then the inactive reverse T3. The thyroid affects nearly every organ system in the body and appears to be a major regulator of metabolism. Low T3 is seen with malnutrition, anorexia, severe burns, and febrile illnesses. In a normal pregnancy, hCG causes a transient decline in TSH levels in the first trimester because they share an identical _ subunit and a similar _ subunit. Total T4 and T3 levels will increase, but because thyroid binding globulin (TBG) rises dramatically there will be an overall fall in free T4 and free T3.

Diagnosis
The diagnosis of thyroid disease is easily accomplished using TSH as a screening test. If the level is outside the normal range then a free T4 (fT4) should be checked. Each lab will have a different range for normal, but the typical range for TSH is 0.45-4.5 mIU/mL with a free T4 range of 0.8-2.0 ng/dL. Hypothyroidism is diagnosed with high TSH and low free T4 levels, while low TSH and high free T4 levels leads to a diagnosis of hyperthyroidism. Subclinical hypothyroidism is diagnosed with elevated TSH levels, but normal free T4 levels.

Hypothyroidism
The typical symptoms of hypothyroidism are fatigue, constipation, slower motor and speech function among many others. Hypothyroidism can cause hypertension, cardiac abnormalities, nerve conduction problems, anemia and hyponatremia. It can also lead to Anovulation; and create fertility problems. Therefore, we recommend that women with irregular menses be screened with a TSH and reflex free T4 if needed. Treatment consists of thyroid hormone supplementation. The pituitary will fully adjust to changes in medication dose changes after 8 weeks, but checking after 5 weeks is common practice. The most common cause of hypothyroidism is anti-thyroglobulin antibodies (TGB) or anti-thyroid peroxidase (TPO) antibodies. Some medical endocrinologists advocate screening patients for autoimmune disorder when hypothyroidism is diagnosed. It is estimated that 10-15% of women have anti-thyroid antibodies regardless of their thyroid status.

Hypothyroid women who become pregnant will require a 20-50% increase in their thyroid medication. This can be accomplished by having a pregnant patient take 2 additional doses of her thyroid medication weekly and then rechecking the TSH level after 6 weeks. Women with poorly controlled hypothyroidism can have children with neurologic deficits and lower IQs. Additionally, there is an association between anti-thyroid antibodies and an increased rate of miscarriage. TSH levels above 2.5 mIU/ml have also been associated with miscarriages. One study demonstrated that treatment of euthyroid patients with levels greater than 2.5 regardless of thyroid anti-body status, decreased the risk of miscarriage. Therefore the Endocrine Society now recommends that all women considering pregnancy have their TSH checked and levels maintained below 2.5 with thyroid hormone replacement. At this time ACOG does not recommend routine TSH screening in pregnant women.

Hyperthyroidism
Classic symptoms associated with hyperthyroidism are anxiety, weight loss, diarrhea, palpitations, exophthalmos, myxedema and possibly goiter. This can lead to tachycardia, hypertension, heart failure, and severe toxicosis. Additionally, hyperthyroidism can lead to anovulation thus leading to fertility difficulties. Methimazole is an excellent choice of treatment for women who are not interested in pregnancy as it has fewer side effects. Some women require radioactive iodine treatment for long-term management of hyperthyroidism. Women interested in conception must wait a minimum of 1 year before trying to conceive following radioactive 131I treatment to avoid detrimental effects on the fetal thyroid.

Thyrotoxicosis is difficult to manage in pregnancy and can lead to preeclampsia, maternal heart failure, miscarriage, abruption, IUGR, stillbirth and preterm birth. Propylthiouracil remains the first-line therapy for drug treatment in pregnancy due to the fetal anomalies associated with methimazole. Additionally, physicians should screen for anti-TSH receptor antibodies found in Grave’s Disease because these can cross the placental and lead to fetal hyperthyroidism and complications.

Subclinical Hypothyroidism
2-3% of reproductive age women have subclinical hypothyroidism. It is advisable to check TPO and TGB antibodies in these patients. For women not attempting conception yearly screening for hypothyroidism should be initiated. The recommendations for women attempting conception are less defined, but subclinical hypothyroidism is associated with pregnancy loss and preterm delivery. Correcting TSH levels has improved miscarriage and pre-term delivery, so the Endocrine Society recommends treatment with thyroid hormone replacement to reduce TSH levels to under 2.5 mIU/ml.

References

Endocrine Society. The Endocrine Society’s Clinical Practice Guidelines for Management of Thyroid Dysfunction during pregnancy and Postpartum. Thyroid. 2007. 17(11):1159-67.

Haddow JE et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the Child. N Engl J Med. 1999. 341:549-555.

Glinoer D et al. Pregnancy in patients with mild thyroid abnormalities: maternal and neonatal repercussions. J Clin Endocrinol Metab. 1991. 73:421-427.

Stagnaro-Green A et al. Detection of at risk pregnancy by means of highly sensitive assays for thyroid autoantibodies. JAMA. 1990. 264:1422-1425.

Negro R et al. Levothyroxine treatment in euthyroid pregnant women with autoimmune thyroid disease: effects on obstetrical complications. J Clin Endocrinol Metab 2006. 91:2587-2591.