Thyroid Disease in Pregnancy
/The thyroid is obviously an important endocrine organ. As we’ve talked through many of our GYN episodes, from infertility to bleeding, the thyroid is part of our basic workup. Thyroid function is important in pregnancy as well, as uncontrolled thyroid disease is associated with adverse pregnancy outcomes. Subclinical thyroid disease, on the other hand, has unclear benefit and likely risks to therapy. Read and listen on, and check out ACOG PB 148 for further reading!
Thyroid physiology in pregnancy
Thyroid function fluctuates in pregnancy in part due to bHCG
Thyroid stimulating hormone (TSH) and bHCG share an alpha subunit as hormones of the anterior pituitary. Thus, bHCG has mild thyrotropic effects.
In the first trimester, TSH may be lower as a reflection of this.
Free T4 may also be slightly elevated in the first trimester.
TSH values should revert to normal after 12 weeks gestation.
Important: TSH should not routinely be measured in women with hyperemesis gravidarum, unless other symptoms of hyperthyroidism are pregnant, for this reason. Treatment of transient hyperthyroidism associated with HG has not been shown to be beneficial.
Maternal T4 is transmitted transplacentally throughout the pregnancy and is important for normal fetal brain development
It is especially important before fetal thyroid gland begins functioning at approximately 12 weeks.
Thus, preconception screening and treatment for symptomatic thyroid disease is very important!
Nonpregnant iodine intake recommendation is 150 mcg daily.
220 mcg daily in pregnancy.
290 mcg daily in lactation.
Iodine is not always included in prenatal vitamins
American diet generally has enough iodine intake without supplementation, though should be a consideration for anyone with hypothyroid symptoms.
Thyroid Disease Testing
Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy.
Only screen women for those at increased risk of overt hypothyroidism, or with symptoms of overt hyper- or hypothyroidism.
TSH and free T4 are the recommended baseline screening tests.
TSH is most important baseline screening test. In pregnancy, values:
1st trimester: 0.1 - 2.5 mIU/L
2nd trimester: 0.2 - 3.0 mIU/L
3rd trimester: 0.3 - 3.0 mIU/L
Free T4 (thyroxine) contextualizes the TSH result, and is often sent as a reflex if TSH is abnormal.
Free T3 is generally not useful.
Very rare to have an abnormally high T3 causing hyperthyroidism; can be obtained if suspicious based on symptoms, with low TSH and normal T4.
Antithyroid antibodies rarely lead to changes in management, so no evidence to routinely test for these.
Pathophysiology of Various Thyroid Conditions in Pregnancy
Overt Hyperthyroidism:
Occurs in 0.2% of pregnancies, with Graves’ disease (anti-thyroid antibody stimulation) accounting for 95% of cases.
Diagnosis: low TSH (often undetectable), high free T4, and symptoms
tremors, tachycardia, weight loss, heat intolerance, insomnia, goiters, palpitations, hypertension (“activating symptoms”).
Risks of Disease:
Maternal: hypertension, preeclampsia, heart failure
Fetal/Neonatal: premature delivery (medically-indicated), growth restriction/low birth weight, stillbirth, hydrops, neonatal hypothyroidism or hyperthyroidism.
Maternal anti-thyroid antibodies can cross placenta and can stimulate or inhibit fetal thyroid.
This risk is not necessarily mitigated in neonates of mothers who have had treatment for Graves’ with surgery or radioactive iodine treatment -- antibodies can persist and still cross placenta.
Thioamide treatment helps to suppress antibody production in medically-treated patients.
Subclinical Hyperthyroidism:
1.7% of pregnancies.
Diagnosis: low TSH, with normal free T4.
Has not been associated with adverse pregnancy outcomes.
Due to potential for antithyroid medication to cross placenta and cause adverse fetal effects, treatment is not recommended.
Overt Hypothyroidism:
0.2 - 1% of pregnancies.
Diagnosis: high TSH, decreased free T4, and symptoms:
Fatigue, constipation, cold intolerance, weight gain, dry skin, hair loss, prolonged relaxation of DTRs, edema.
Challenge -- these symptoms sound a lot like early pregnancy!
Goiter more likely in women with Hashimoto thyroiditis --
most common cause of hypothyroidism in pregnancy (glandular destruction by thyroid autoantibodies).
Risks of Disease:
Maternal: preeclampsia
Fetal/Neonatal: SAB/pregnancy loss, preterm birth, placental abruption
Untreated hypothyroidism may predispose to impaired neuropsychological development in offspring.
This is due to low active thyroid hormone, though; it is extremely uncommon for maternal thyroid inhibitory antibodies to cross placenta and cause fetal hypothyroidism.
Prevalence of fetal hypothyroidism in offspring of women with Hashimoto is only 1 in 180k neonates.
Subclinical Hypothyroidism
2-5% of pregnancies.
Diagnosis: high TSH, normal free T4; unlikely to progress to overt hypothyroidism in pregnancy in otherwise healthy women.
Bottom line: not associated with adverse pregnancy/neonatal outcomes.
Controlled Antenatal Thyroid Screening Study 2012 RCT with follow up to age 3, and additional follow up in 2018 to age 9.5.
Antenatal screening of thyroid function at mean GA of 12w3d.
No difference in neurocognitive development of offspring at both age 3 and age 9.5.
Secondary analyses find no definitive association with preterm birth, placental abruption, NICU admission, preeclampsia, GDM.
Recommendation by ACOG, Endocrine Society, Association of Clinical Endocrinologists recommend against universal screening for thyroid disease in pregnancy for this reason.
Thus -- as stated before, only screen women for those at increased risk of overt hypothyroidism or with symptoms of overt hypothyroidism.
Treating Overt Thyroid Conditions in Pregnancy
Hyperthyroidism
Mainstay of therapy is thioamide medications, either propylthiouracil or methimazole.
PTU inhibits thyroperoxidase, an essential enzyme in creation of free T4. Also partially inhibits conversion of T4 to T3.
Preferentially used in1st trimester -- less readily crosses the placenta than methimazole.
Major side effect of note is hepatotoxicity, affecting 0.1-0.2% of women on PTU.
Thus the recommendation is to switch to methimazole in the second trimester. No indication for routine LFTs.
Methimazole also inhibits thyroperoxidase.
Preferentially used in 2nd trimester due to hepatotoxicity.
Avoided in 1st trimester due to rare risk of embryopathy, characterized by esophageal or choanal atresia as well as aplasia cutis (congenital absence of skin, usually on the scalp).
Rare but important side effect of both drugs: leukopenia in up to 10% of pregnant women on these drugs, which does not usually require therapy cessation.
However, rarely progresses to agranulocytosis in less than 1%, and this mandates discontinuing the offending agent.
If women develop flu-like symptoms, they should discontinue these meds and immediately obtain CBC to assess WBC count.
Initial dosing for both drugs is empiric:
50-150mg TID for PTU
10-40mg total daily divided into 2-3 doses for MTZ.
Goal is to use the lowest thioamide dose to maintain free T4 in the high-normal range, regardless of TSH level.
Measure free T4 concentrations q2-4 weeks after initiating therapy (not TSH levels!) and adjust thioamide dose accordingly.
Hypothyroidism
Levothyroxine is the mainstay for thyroid hormone replacement.
Dosing should begin at 1-2 mcg/kg daily, or approximately 100mcg daily.
Monitor therapy by measuring TSH levels every 4-6 weeks (not T4!)
Adjust dose by 25-50 mcg increments until TSH normalizes.
Anticipatory 25% increase in T4 replacement at pregnancy confirmation in women with known thyroid disease may reduce the risk of significant hypothyroidism in early pregnancy in higher risk women (i.e., history of thyroidectomy or radioiodine ablation).
Thyroid Storm and Thyrotoxic Heart Failure
Thyroid storm is rare - 1-2% of pregnant patients with hyperthyroidism.
Cardinal symptoms include fever, tachycardia, arrhythmias, and CNS dysfunction. Develops abruptly and leads to multiorgan failure.
Thyrotoxic heart failure is more common, actually, and has been identified in 8% of women with uncontrolled hyperthyroidism.
Due to an excess of free T4 and effects on myocardium.
Decompensation usually precipitated by other disease, such as PEC, sepsis, anemia.
Fortunately this is often reversible with treatment.
Tenets of treatment of these conditions:
Evaluate TSH and T4, but if suspected -- do not withhold treatment!
Follow the ACOG algorithm here (read out loud):
ACOG PB 148
Postpartum Thyroiditis
Defined as thyroid dysfunction within 12 months of delivery that can manifest as hyperthyroidism, hypothyroidism, or both.
Transient autoimmune thyroiditis present in 5-10% of women in this time period.
Often attributed to “the stresses of motherhood” so actually infrequently encountered clinically.
Often develops in two phases:
First, hyperthyroid state that is charactrized by simultaneous thyroid gland destruction, lasting maybe a few months at the longest.
Often a small, painless goiter can be found in these patients.
If diagnosed during this phase, thioamides are generally ineffective, but beta blockers can help with symptoms if necessary.
Then, hypothyroid symptoms that begin somewhere between 4-8 months postartum, requiring thyroid replacement for 6-12 momnths.
Most women will have symptoms resolve sponteneously, but up to ⅓ of women will develop permanent hypothyroidism.
Thyroid nodules in pregnancy
Can be found in 1-2 % of reproductive-aged women.
If pregnant, should perform H&P, TSH, and ultrasound of the neck
Ultrasound reliably detects nodules greater than 0.5 cm.
If suspicious for malignancy, next step is fine needle aspiration.
Radioiodine scanning is not recommended in pregnancy due to theoretical risk of fetal irradiation.
If cancer is detected, multidisciplinary discussion should be had regarding treatment timing.
Many times surgery is delayed until after delivery due to concern for potential removal of parathyroid glands.