Thyroid Disease in Pregnancy

Contributor: Daniel Pasko, MD
Last Update: February 2021

Background

• Thyroid disease is the 2^nd most common endocrinopathy in pregnancy.
  • Hypothyroidism complicates 1% of pregnancies.
  • Hyperthyroidism complicates 0.2% of pregnancies.
• Diagnosis and management is influenced by numerous physiologic changes in thyroid function.

Pregnancy Physiology

• Maternal thyroid volume increases 10% to 30%.
• ↑ thyroid hormone production results in ↑ demand for iodine.
  • Recommended daily dietary iodine intake:
    • 150 mcg non-pregnant.
    • 220 mcg pregnant.
    • 290 mcg lactation.
  • Transient ↓ in thyroid stimulating hormone (TSH) levels prior to 12 weeks’ gestation.
    • Mediated by hCG stimulation of TSH receptors.
  • Total T3 and total T4 ↑ due to an estrogen induced ↑ in thyroid binding globulin.
    • Free T4 and free T3 levels do not increase.

Evaluation of Thyroid Disease in Pregnancy

• Universal screening for thyroid disease in pregnancy is not recommended.
• Indications for baseline thyroid studies include:
  • Symptoms of thyroid disease (see Table 1).
  • Personal or family history of thyroid disease.
  • Known thyroid disease on medication.
  • A history of treatment for Graves’ disease.
  • Presence of a goiter or thyroid nodules.
  • Maternal pregestational diabetes mellitus.
• TSH is the first-line test to evaluate for thyroid disease.
  • ↑ TSH -> free T4 to evaluate for overt hypothyroidism.
  • ↓ TSH -> free T4 and total T3 to evaluate for overt hyperthyroidism.

Table 1. Symptoms of Thyroid Disease
Hypothyroidism	Hyperthyroidism
Cold intolerance	Heat intolerance
Lethargy	Tremors
Hair loss	Tachycardia
Dry skin	Palpitations
Muscle cramps	Hypertension
Weight gain	Weight loss
Constipation	Frequent stools
Edema	Goiter

 

Hypothyroidism

• Hashimoto’s thyroiditis is the most common etiology.
  • Glandular destruction by thyroid peroxidase antibodies (TPOAb) or anti-thyroglobulin.
• Other etiologies: post-ablation / thyroidectomy, iodine deficiency, atrophic hypothyroidism.
• Poor disease control associated with adverse outcomes.
  • Maternal: pregnancy loss, placental abruption, preeclampsia, hemorrhage.
  • Fetal: low birth weight, impaired neuropsychological development.
• Women with treated Graves’ disease (ablation / thyroidectomy) may present as hypo- or euthyroid.
  • Persistence of thyrotropin receptor autoantibodies (TRAb) that cause Graves’ disease pose continued pregnancy risks.
    • Refer to “Fetal Considerations” section under hyperthyroidism for details of TRAb levels, which should be drawn for all women with a history of Graves’ disease.

Diagnosis

• Lab criteria: ↑ TSH (>4 mU/L) AND ↓ free T4 (<0.7 ng/dL).
• A goiter may or may not be present (more likely with Hashimoto’s).

Maternal Medical Management

• Initiation of Therapy
  • Begin levothyroxine 1 mcg/kg (typically 100-150 mcg daily).
    • Instruct to take multivitamin / ferrous sulfate 4 hours after dose.
    • T3 thyroid replacement preparations are generally avoided.
  • Assess TSH levels every 4-6 weeks while adjusting dose.
    • Treatment goal: TSH 0.4 to 2.5 mU/L.
    • Titrate dose by 25-50 mcg until TSH normalizes.
  • Repeat TSH assessment every trimester once at goal.
• Known Thyroid Disease
  • Consider empiric 25% increase in levothyroxine dose at conception.
  • Assess TSH at initial visit and repeat every trimester unless dose adjustments required.
    • Treatment goal: TSH 0.4 to 2.5 mU/L.
  • Postpartum
    • Resume pre-pregnancy dose.
    • Evaluate TSH 6-8 weeks postpartum.

Fetal Considerations

• Ultrasound surveillance:
  • Growth US and antenatal testing not routinely indicated.
    • Exception: growth US 28 & 34 weeks if hypothyroidism in setting of treated Graves’ disease with positive TRAb.
  • Routine evaluation of TPOAb and anti-thyroglobulin antibodies is not indicated.
    • Prevalence of fetal hypothyroidism is estimated at 1:180,000.

Neonatal Considerations

• Pediatricians should be notified of maternal history of hypothyroidism including TRAb status if applicable.

Subclinical Hypothyroidism

• Estimated prevalence: 2-5% pregnancies.
• Lab criteria: ↑ TSH (>4 mU/L) and normal free T4 (0.7-1.5 ng/dL).
• Per ACOG, treatment is generally not indicated based on available evidence.
  • Individualized treatment plans may be indicated in some clinical scenarios (i.e., TSH >10 mU/L with normal free T4). MFM consultation is recommended.

Hyperthyroidism

• Graves’ disease is the most common etiology (95% of cases).
  • Thyroid stimulation mediated by thyrotropin receptor autoantibodies (TRAb).
  • Distinctive features: exophthalmos, lid lag, lid retraction, and pretibial myxedema.
• Other etiologies: subacute thyroiditis, nodular goiter, thyroid adenoma, gestational trophoblastic disease.
• Poor disease control associated with adverse outcomes.
  • Maternal: pregnancy loss, preeclampsia, heart failure, thyroid storm.
  • Fetal: low birth weight, indicated preterm delivery, hydrops fetalis.

Diagnosis

• Lab criteria: ↓ TSH (<0.1 mU/L) AND ↑ free T4 (>1.5 ng/dL).
• Thyrotoxicosis may also be mediated by T3, which is best characterized by an elevated total T3 (>1.5x upper limit of non-pregnant value).
• If TSH <0.1 mU/L and elevated free T4 or total T3:
  • Order TRAb, thyroid US, and request endocrinology and maternal-fetal medicine consults.
  • Per endocrinology, please message the endocrinologist “on-call” to review the US and TRAb results to ensure appropriate management and follow-up.

Maternal Medical Management

• Thioamides
  • Propylthiouracil (PTU) and methimazole are the first-line treatments.
  • Medication selection is based on the trimester.
    • PTU through 16 weeks followed by methimazole in 2^nd / 3^rd trimesters.
      • Methimazole potential teratogen (esophageal or choanal atresia, aplasia cutis).
    • Exceptions: prior treatment failure, T3 predominant disease (favors PTU), patient preference.
  • Associated with risk of agranulocytosis.
    • Development of fever or sore throat -> hold medication and obtain CBC.
    • Serial leukocyte counts not indicated due to acute onset.
  • PTU associated with risks of hepatotoxicity.
• Initiation of Therapy
  • Empirical thioamide dosing.
    • PTU: 100-600 mg total daily dose, divided among three doses (e.g., 100 mg PO TID).
    • Methimazole: 5-30 mg total daily dose, divided among two doses (e.g., 5 mg BID).
    • Med conversion: dose ratio of 20:1 from PTU to methimazole.
  • Obtain baseline labs (CBC as well as CMP for patients on PTU).
  • Assess free T4 levels every 2 weeks while adjusting dose.
    • Treatment goal: free T4 at upper limit of normal (1.4 ng/dL) using lowest dose possible.
  • Schedule return clinic visit every 1-2 weeks during medication initiation.
  • Repeat free T4 levels every 4 weeks once stable and at goal.
• Beta-Blockade
  • Indicated for symptomatic palpitations.
    • Propranolol 10-40 mg three to four times daily.

Alternative Management Options

• Thyroidectomy may be considered, ideally in the 2^nd
  • Indications: inability to tolerate pharmacotherapy, refractory hyperthyroidism, non-compliance.
• Thyroid ablation is contraindicated in pregnancy.

Fetal Considerations

• Ultrasound surveillance:
  • Serial growth assessments, monitor for fetal goiter.
  • Antenatal testing at 34 weeks if free T4 / total T3 not at goal.
• Maternal antibodies from Graves’ disease (TRAb) pose risks of fetal thyrotoxicosis.
  • Evaluate for elevation at initial visit (order in Epic as “TRAb”).
    • TRAb elevation defined as 3x upper limit of normal.
    • If elevated at initial visit, repeat at 28-32 weeks for neonatal risk stratification.
  • Risk persists after maternal thyroidectomy or thyroid ablation.
  • MFM consultation warranted for fetal tachycardia, fetal growth restriction.

Neonatal Considerations

• Pediatricians should be notified of maternal history of Graves’ disease, TRAb status.
  • Up to 5% risk of neonatal thyroid disease.

Thyroid Storm

• Life threatening complication among 1-2% of pregnant patients with hyperthyroidism.
• Triggered by stressors such as labor, infection, or surgery.
• Disease manifestations:
  • Fever
  • Altered mental status
  • Nausea / vomiting, diarrhea, dehydration
  • Hypertension
  • Maternal tachycardia, arrhythmias, heart failure
  • Fetal tachycardia

Management

• Admission to L&D or ICU
• Consult Endocrinology and MFM
• PTU 1000 mg PO, then 200mg PO every 6 hours
• Iodine administration 2 hours after PTU, formulations include:
  • NaI: 500-1000 mg IV every 8 hours
  • KI: five drops PO every 8 hours
  • Lugol solution: 10 drops PO every 8 hours
  • Lithium carbonate: 300 mg PO every 6 hours
• Corticosteroid administration, formulations include
  • Dexamethasone 2 mg IV every 6 hours x4 doses
  • Hydrocortisone 100 mg IV every 8 hours x3 doses
• Beta-blockade (propranolol, labetalol, or esmolol) to control tachycardia
• Supportive measures: IV fluids, temperature control, O2

Subclinical Hyperthyroidism

• Estimated prevalence: 0.8-1.7% pregnancies.
• Lab criteria: ↓ TSH (<0.1 mU/L) and normal free T4 (0.7-1.5 ng/dL).
• Treatment is not indicated based on available evidence.

References

1. Thyroid Disease in Pregnancy. ACOG Practice Bulletin No. 223. American College of Obstetricians and Gynecologists. Obstet Gynecol 2020; 135:261–70.
2. Alexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, et al. 2017 guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid 2017; 27:315-89.