Thyroid & Pregnancy

Thyroid Disease

Thyroid disease is the 2nd most common endocrine disorder that affects women of childbearing age. Hyperthyroidism occurs in 0.2% of pregnancies. Hypothyroidism occurs in 2.5% of pregnancies. Postpartum thyroid disease occurs in 5-10% of women after delivery who don’t have history of thyroid disease. 25% of women with Type 1 DM develop postpartum thyroid dysfunction. Incidence of thyroid cancer in pregnancy is 1 per 1000. Malignancy is found in up to 5-40% of thyroid nodules discovered during pregnancy.

Physiologic Adaptation During Pregnancy

Pregnancy causes increase in thyroid-binding globulin (TBG), which binds Total T4 and T3 thyroid hormones measured in the blood. In 1st trimester, increased hCG, a molecule very close to TSH (Thyroid stimulating hormone from pituitary) stimulates the thyroid to make more thyroid hormone for the developing fetus. A low TSH early in pregnancy is normal. In most pregnant women, this change has minimal clinical consequences.

Since the backbone of thyroid hormone is iodine, higher iodine consumption is necessary during pregnancy to maintain the thyroid glands ability to produce T3 and T4 (tetraIODOthyronine). The WHO recommends consume 200 mcg/day of Iodine for pregnant women. Normal daily requirements for adults is 150 mcg/day.

Fetal production of thyroxine (thyroid hormone) is observed by 14th week of gestation.

This makes it vitally important that in your early pregnancy, you have normal thyroid function to provide the fetus with necessary thyroid hormone for proper brain development in the early first trimester. If you have had an ablation or surgical removal of your thyroid and take thyroid hormone replacement, your TSH target to provide fetus with adequate thyroid hormone is
Graves’ disease is the most common cause of hyperthyroidism (95% of cases of hyperthyroidism). Other causes of hyperthyroidism in pregnancy include solitary toxic adenoma, toxic multinodular goiter (MNG), viral subacute thyroiditis (de Quervain’s), tumors of pituitary gland or ovary (struma ovarii), transient hyperthyroidism from hyperemesis gravidarum or gestational transient thyrotoxicosis (GET). Ideally hyperthyroidism should be controlled before conception.
Maternal hyperthyroidism associated with preterm delivery, intrauterine growth restriction (IUGR), preeclampsia, congestive heart failure (CHF), stillbirth, and increased risk of spontaneous abortion.

Transient Hyperthyroidism during Pregnancy:

hCG (the test you do to see if you are pregnant) is a glycoprotein hormone secreted by the placenta and is able to act like TSH and stimulate the thyroid gland to make more hormone. This is a built in mechanism to protect the fetus from low hormone (unless you don’t have a gland: ablation/surgery). hCG induced hyperthyroidism usually resolves by 18 wks gestation without therapy.

Nausea and vomiting of pregnancy has been associated with high hCG levels. Two disorders bare special attention here: “mole” and “choriocarcinoma.” Both conditions are associated with significant hyperthyroidism during pregnancy (due to excessive hCG).

Hydatidiform mole (an abnormal pregnancy with absent fetus) occur in <0.2% of pregnancies and is more prevalent in younger and older women (50 years old). They present clinically as threatened abortion with vaginal bleeding. These moles secrete large amounts of hCG, that stimulate increased thyroid function in up to 64% of cases. About 5% have clinical hyperthyroidism serious enough to require treatment. hCG levels may be 150-3000 mIU/ml and removal of the mole normalizes thyroid function.

Moles, if left untreated continue to grow and can produce hCG in the 100,000-1,000,000 range. They may transform from mole to choriocarcinoma, an aggressive cancer, which occurs in <0.02% of pregnancies. These tumors invade the blood vessels and readily metastasize (spread) with hemorrhagic lesions. Without prompt treatment, it is a rapidly progressive and fatal disease. They usually spread to the lungs and vagina and may cause cough with bloody sputum, vaginal bleeding and weight loss. Cure rates from 86%- 95% have been achieved with chemotherapy. Hyperthyroidism resolves with treatment of the choriocarcinoma.

Less severe hCg related conditions in pregnancy that do not require surgery or chemotherapy: Gestational Transient Thyrotoxicosis (GET) – Hyperthyroidism caused by increased hCG which binds to the TSH receptor and stimulates thyroid hormone production/release. Occurs in 1st trimester, have symptoms of hyperthyroidism with Thyroid gland usually NOT enlarged. Resolves as hCG levels naturally decrease in 2nd trimester. Treatment with B-blocker can be used for symptomatic relief.

Hyperemesis Gravidarum:

Usually have hCG > 75,000 IU/ml. Levels this high can be seen in twin or molar pregnancy. Can have persistent nausea, vomiting, 5% weight loss, and electrolyte abnormality. Treatment is supportive and TFT usually normalize by 18 wks gestation. If anti-thyroid medication is needed, methimazole has the advantage over PTU because it’s available in suppository form. Graves’ Disease 95% of cases of thyrotoxicosis during pregnancy.

TSI antibody can cross placenta and cause neonatal Graves’ disease in 1% of infants. This antibody should be evaluated in the 3rd trimester High levels alert the neonatologist to fetal thyroid disease at birth.

Goal of treatment of hyperthyroidism during pregnancy is to keep the patient euthyroid (normal) with FT4 in upper limit of normal range so as not to cause fetal or neonatal hypothyroidism. PTU is the drug of choice only in the first trimester as FDA has warned of increased incidence of hepatic failure with PTU. Pt are changed to Methimazole at 12 weeks gestation. PTU vs. Methimazole During Lactation maternal use of antithyroid drugs (PTU or Methimazole) appears to be safe. These meds should be taken after breastfeeding. A 3-4 hr interval should elapse after taking these meds before the mother lactates again to minimize their concentration in breast milk.

Thyroidectomy for Graves:

Indicated if control of hyperthyroidism is poor due to poor compliance or allergic to meds.Also indicated in pts with large goiter with compressive symptoms. Surgery is preferred in 2nd trimester. If done on 1st trimester there is increase in miscarriages and increase in preterm labor if done after 24 weeks.
 
B-Blockers during Pregnancy Used to control adrenergic symptoms like tachycardia (rapid heart beating). Propranolol 20-40 mg 3x/d is the agent of choice. IV Esmolol can be used in emergent situations. B-blockers are safe for a few weeks but prolonged use associated with IUGR, fetal bradycardia (slow heart beat), neonatal hypoglycemia, small placenta, hypocalcemia (low calcium), and respiratory depression. Vitally important to get thyroid under control with anti-thyroid meds asap.

Radioactive Iodine in Pregnancy

I131 is contraindicated in pregnancy because the fetal thyroid can take up Iodine after 10 weeks of gestation. Fetal thyroid has 20-50X more affinity for iodine than the maternal thyroid so any dose of radioiodine will be more highly concentrated and can ablate the fetal thyroid. If a pregnant woman inadvertently received I131 then she should get SSKI and PTU within 1 week of exposure to block organification and reduce radiation exposure to the fetal thyroid gland (by 100 factor). It also reduces radiation exposure to the whole body of the fetus by a factor of 10.
 
If radioactive iodine exposure occurs before 10 wks gestation it’s unlikely that the fetal thyroid will be ablated. Avoid breastfeeding for at least 120 days after I131. Half life of I123 is 8 hrs, I131 is 8 days.
 
Thyroid Storm in Pregnancy (severe life-threatening form of acute hyperthyroidism) Occurs in 1% of pregnant pts with hyperthyroidism.
 
The diagnosis is made if fever, tachycardia, mental status change (restlessness, nervousness, confusion, seizure), nausea, vomiting, diarrhea, cardiac arrhythmia.
 
Usually there is an inciting event like infection, surgery, labor, delivery.

Treatment:

• PTU 600-800 mg po stat then 150-200 mg every 4-6 hrs.
• If can’ use oral meds, use Methimazole rectal suppositories.
• 1-2 hrs after PTU administration, SSKI 2-5 drops every 8 hrs or sodium iodide 0.5-1 g IV every 8 hrs, or lugol’s solution 8 drops every 6 hrs.
• Dexamethasone 2 mg IV/IM every 6 hrs x 4 doses (decreases T4 to T3 conversion and decrease thyroid hormone release).
• Propranolol 20-80 mg every po 4-6 hrs or 1-2 mg IV every 5 minutes total 6 mg then 1-10 mg IV every 4 hrs.
• If have bronchospasm use Diltiazem 60 mg po every 6-8 hrs.
• Phenobarbital 30-60 mg po every 6-8 hrs prn for restlessness (increase catabolism of thyroid hormone).
• Oxygen, Tylenol (not aspirin), cooling blanket, IVF, correct electrolyte abnormality, maternal and fetal monitoring.
• Treat underlying cause of thyroid storm.

Postpartum Graves’ Disease About 70% of women have postpartum relapse of Graves’ disease within the first 3 months after delivery. See hyperthyroidism.

Hypothyroidism in Pregnancy

Hypothyroidism occurs in 2.5% of pregnancies.
 
There is increase in thyroid hormone requirements in pregnancy due to increase in estrogen stimulated TBG pool which decreases levels of free thyroid hormone. Also GI absorption of thyroid hormone may be decrease if it’s taken the same time as prenatal vitamin which has iron in it. Carbamazepine, phenytoin, rifampin can increase clearance of T4.
 
In up to 75% of pts, maternal requirements of LT4 increase by 50-100 mcg/day during pregnancy. Inadequately treated maternal hypothyroidism is associated with LBW (low birth weight) from preterm delivery, preeclampsia, or placental abruption. Worldwide most common cause of hypothyroidism is iodine deficiency.
 
Transplacental passage of maternal T4 necessary for fetal brain development early in 1st trimester before the development of fetal thyroid gland. If there is iodine deficiency, even when the fetal thyroid gland is developed it is unable to make thyroid hormone. Results of severe maternal iodine deficiency is fetal cretinism, characterized by severe mental retardation, deafness, muteness, pyramidal or extrapyramidal syndromes. Untreated congenital hypothyroidism also results in cretinism.
 
If treated within the first few weeks of life, near-normal growth and intelligence can be expected. In U.S. Hashimoto’s thyroiditis accounts for most cases of hypothyroidism during pregnancy. Hashimoto’s thyroiditis occurs in 8-10% of women of reproductive age. Antithyroglobulin antibodies are elevated in 50-70% of pts and almost all pts have high antiperoxidase antibodies as well. Other causes of hypothyroidism are I131 tx for Graves’ disease, thyroiditis, and thyroidectomy.
 
Treatment with levothyroxine sodium at a weight based dose necessary to restore normal thyroid function and avoid harm to fetus, Goal TSH <2.5 throughout pregnancy adjust dose every 4 weeks, as necessary during pregnancy. Requirements can change at every trimester.
 
Women who were on LT4 before pregnancy should have their TSH and FT4 checked every 8 weeks. Postpartum Thyroiditis (inflamed thyroid) Occurs in 5-10% of women who don’t have a history of thyroid disease. 25% of women with type I DM have postpartum thyroid dysfunction after delivery.
 
They can present with hyperthyroid or hypothyroid symptoms. Transient hyperthyroid phase occurs 6 weeks to 6 months postpartum. This is followed by hypothyroid phase that lasts for up to 1 yr postpartum. 1/4 of women will have this classic presentation, >1/3 with have only hypothyroid or hyperthyroid symptoms.
 
It is usually self-limited so antithyroid drugs not usually indicated. B-blockers can be used for adrenergic symptoms (nervous, shakes, anxiety, heart pounding). Permanent hypothyroidism will develop in 11-23% of pts. Women with the highest TSH and anti-thyroperoxidase antibodies have the greatest risk of developing permanent hypothyroidism.

Thyroid Nodule/Cancer in Pregnancy

Incidence of thyroid cancer in pregnancy is 1 per 1000. Pregnancy doesn’t alter the course of thyroid cancer. Thyroid nodule discovered during pregnancy should be evaluated because malignancy will be found in 5-40% of these nodules. Majority are PTC. Management of thyroid nodule discovered during pregnancy similar to that in nonpregnant women.
 
FNA should be done on nodules >1-2 cm especially if detected before 20 weeks gestation or if there are other risk factors for malignancy like rapid growth or lymphadenopathy. Definitive treatment for thyroid cancer is thyroidectomy and radiation.
 
Thyroidectomy can be performed during pregnancy preferably in the 2nd trimester or at the earliest safe period.
 
Radiation should wait till after pregnancy. If nodule < 2 cm, has not increased in size rapidly, and pt doesn’t have lymphadenopathy on US, then it is reasonable to wait until after pregnancy to do thyroidectomy. Place the women on LT4 suppression to prevent further growth of cancer till after pregnancy when surgery can be performed.

Screening for Thyroid Disease in Pregnancy

Recommended screening for women with a personal history of thyroid disease or symptoms of thyroid disease, as well as those with abnormal thyroid exam, family history of thyroid disease, prior miscarriage, has child with thyroid disease.