ACOG Update: Thyroid Disease in Pregnancy

SUMMARY:

Thyroid disease, both thyrotoxicosis and hypothyroidism, are associated with adverse pregnancy outcomes and poor fetal development, including neurocognitive outcomes.  Given the importance of understanding physiology, changes during pregnancy, and management, ACOG has published recommendations to guide clinical decision-making. Universal TSH screening for thyroid disease in pregnancy is not recommended. Subclinical thyroid disease (abnormal TSH but normal free T4) does not require treatment. However, overt hyperthyroidism and hypothyroidism warrant further management

Physiologic Changes in Pregnancy

  • Maternal thyroid volume increases 10-30% in pregnancy, especially in 3rd trimester, as a result of increased blood volume and extracellular fluid
    • An enlarged thyroid gland in isolation is not an indication for screening for thyroid disease if no other clinically relevant history, symptoms, or signs are present
  • TSH (thyroid stimulating hormone, or ‘thyrotropin’)
    • Decreased in early pregnancy
      • β-hCG weakly stimulates TSH receptors causing increased T4 (thyroxine) levels | Estrogen stimulates higher levels of thyroid-binding globulin that transport thyroid hormone in the blood
      • American Thyroid Association recommends the following in the late first trimester if local reference ranges for TSH are unavailable: Reduce lower reference range by 0.4mU/L | Reduce upper reference range by 0.5mU/L
    • After first trimester: Use non-pregnant reference ranges as TSH increases due to increased production of placental deiodinase
  • Maternal transfer of T4 to fetus
    • Necessary for fetal brain development
    • 30% of umbilical cord T4 is maternally derived
  • Maternal iodine requirements
    • Pregnant women: 220 micrograms
    • Lactating women: 290 micrograms
    • Majority of women in US have sufficient intake

Workup of Thyroid Abnormalities (Clinically Indicated Testing)

  • Test TSH first
    • TSH high or low (abnormal): Reflex to free T4 (plus total T3 for hyperthyroidism)
    • Free T4 is normal: Thyroid disease is subclinical and does not warrant further workup
  • Anti-thyroid peroxidase antibodies
    • Testing for these anti-bodies (without history and normal thyroid tests) does not improve pregnancy outcomes, therefore is not recommended

Hyperthyroidism

Low TSH and Increased free T4

  • Universal screening not recommended | Diagnosis based on clinical symptoms | 95% will be due to Graves disease
  • Symptoms
    • Nervousness | Tremors | Heat intolerance | Sweating | Weight loss |Goiter | Insomnia | Hypertension | Tachycardia
    • Associated with Graves Disease
      • Graves ophthalmopathy: Upper eyelid retraction | Edema | Erythema of the periorbital tissues and conjunctivae | Proptosis (see ‘Learn More, Primary Sources’ for additional reference including pictures)
      • Dermopathy: For example pretibial myxedema
  • Potential outcomes if left untreated 
    • Iatrogenic preterm deliveries | LBW | Stillbirth
    • Fetal thyrotoxicosis
      • Caution: Not necessarily related maternal clinical thyroid status
      • Signs: Fetal hydrops | FGR | Fetal goiter | Persistent fetal tachycardia
      • MFM consultation recommended
  • Treatment: Follow free T4 and total T3 every 2 to 4 weeks until titrated to high normal range
    • First trimester
      • PTU: 100 to 600mg divided TID
    • After first trimester
      • PTU: 100 to 600mg divided TID or
      • Methimazole 5 to 30mg divided into BID
    • Adverse events
      • Do not use methimazole in first trimester due to association with birth defects including esophageal/choanal atresia and aplasia cutis
      • Due to (rare) association of PTU with hepatotoxicity, option to transition to methimazole or continue PTU after first trimester
      • Both PTU and methimazole have risk of leukopenia (10% patients) but does not require therapy termination
      • Agranulocytosis: Rare side effect | Remain alert for sore throat or fever which does require CBC and cessation of medication
    • Symptom control: Propranolol 10 to 40mg TID/QID

Note: Maternal antibodies found in Graves disease cross the placenta and are cleared slowly | Notify neonatology of maternal diagnosis as neonatal Graves disease may not present immediately following delivery

Hypothyroidism

High TSH, Low Free T4

  • Diagnosis based on history (personal or family), clinical symptoms or type 1 diabetes, other autoimmune disorders
  • Symptoms
    • Cold intolerance | Muscle cramps | Weight gain | Edema | Dry skin | Hair loss
    • Prolonged relaxation of deep tendon reflexes is a notable feature
  • Most common: Hashimoto thyroiditis
    • Anti-thyroid peroxidase antibodies destroy thyroid gland
  • Potential outcomes if left untreated 
    • Miscarrriage | Preeclampsia | Preterm birth | Abruptio placentae | Stillbirth | Abnormal neuropsychological development in offspring
  • Fetal hypothyroidism: Maternal antibodies rarely cross placenta (unlike Graves)
  • Treatment (follow TSH every 4 to 6 weeks and titrate to lower reference limit)
    • Levothyroxine: 1 to 2 micrograms/kg daily | Typically 100 micrograms daily
    • Avoid T3 compounds (fetal CNS development dependent on maternal T4)
    • Pre-pregnancy diagnosis: Medication requirement will likely increase 25%

KEY POINTS:

Hyperemesis Gravidarum And Hyperthyroidism

  • Hyperthyroidism presents in 3-11% of women in early pregnancy
    • TSH receptor stimulation due to high β-hCG levels | Considered to be physiologic
    • ‘Gestational transient hyperthyroidism’ also seen with multiple gestation and molar pregnancies
    • TSH may remain suppressed for weeks after free T4 returns to normal
  • Hyperemesis gravidarum: Measurements of thyroid function not recommended without other clinical indications for testing
    • Does not require treatment | Not associated with poor pregnancy outcomes

Thyroid Storm

  • Medical emergency due to hypermetabolic state
    • Elevated thyroid hormone levels can lead to heart failure
  • Clinical features
    • Fever | Tachycardia | Cardiac arrhythmia | CNS abnormalities
    • Cardiac myopathy leading to heart failure and pulmonary hypertension | More common in pregnancy | Reversible if treated
  • Other clinical associations
    •  Preeclampsia | Anemia |Sepsis
  • Treatment
    • PTU: 1,000mg loading PO then 200mg q6 hours
    • Iodine: Initiate 1 to 2 hours after PTU via sodium iodide (500-1,000mg IV q8h) or potassium iodide (5 drops by mouth q8 hours) or lugol solution (10 drops by mouth q8h) or lithium carbonate (iodine anaphylaxis history, 300mg PO q6h)
    • Dexamethasone:  2mg IV q6h x4 doses or hydrocortisone 100mg IV q8h x3 doses
  • Propranolol, labetalol, and esmolol
    • Have been used to treat tachycardia, but caution warranted in setting of heart failure

Postpartum Thyroiditis 

  • Thyroid dysfunction within 12 months of delivery
    • Diagnosis: New-onset abnormal TSH and free T4
  • First phase
    • Initially thyrotoxicosis as thyroid gland is destroyed and T4 released
    • Mild symptoms controlled with beta-blockers rather than PTU or methimazole
  • Second phase (4 to 8 months postpartum)
    • Overt hypothyroidism with typical symptoms and thyromegaly
  • Depression
    • Order TSH screen for new onset postpartum depression or any new diagnosis of depression
  • Risk of permanent overt hypothyroidism
    • Majority of cases will spontaneously resolve
    • Approximately a third will not resolve (highest risk associated with higher antibody titers)

Thyroid Nodules Detected During Pregnancy

  • Prevalence: 1-2% | 90-95% of solitary nodules are benign
  • Aside from history and physical examination, order
    • TSH
    • Neck ultrasound
  • Radioiodine scanning not recommended due to theoretical risk with fetal irradiation
    • However, if patient inadvertently receives radioiodine in the first trimester, risk of fetal thyroid damage low because fetal thyroid is not active until after the first trimester
  • If cancer identified
    • Surgical treatment in first and second trimesters with thyroidectomy “may be performed” but usually delayed to avoid possible damage to parathyroid glands
    • Management is multidisciplinary and should include possibility of familial cancer syndrome (uncommon)

Learn More – Primary Sources:

ACOG Practice Bulletin 233: Thyroid Disease in Pregnancy

Graves’ Ophthalmopathy (NEJM)