Basics
Description
- Hyperthyroidism is a common endocrine disorder encountered in pregnancy.
- Adverse maternal outcomes of poorly controlled hyperthyroidism include:
- Congestive heart failure
- Thyroid storm
- Preeclampsia
- Potential adverse fetal outcomes include miscarriage, intrauterine growth restriction (IUGR), and stillbirth.
Epidemiology
- Predominance: Female > Male (7:1)
- It typically occurs prior to age 50 with the peak incidence between 20 and 40 years of age.
- Asian and white populations are more likely to develop hyperthyroidism than other races.
Incidence
Lifetime incidence in women is approximately 2%.
Prevalence
Hyperthyroidism will complicate 1 " 2 of every 1,000 pregnancies.
Risk Factors
- Prior history of hyperthyroidism or autoimmune thyroid disease
- Family history of hyperthyroidism
- Other autoimmune disorders (particularly those seen with polyglandular autoimmune syndrome, type II) such as:
- Type I diabetes
- Addison 's disease
- Pernicious anemia
- Celiac disease
- Primary biliary cirrhosis
- Tobacco use
Genetics
- Increased frequency of Graves ' disease is seen in those with HLA-B8 and HLA-D3 antigens.
- 20% concordance in monozygotic twins
General Prevention
Screening for thyroid disease is outlined in the "Pregnancy, Hypothyroidism " chapter.
Pathophysiology
- Similar to the nonpregnant population
- In pregnancy, human chorionic gonadotropin (hCG) may stimulate the thyroid gland.
- The hCG molecule shares an alpha subunit common to TSH and, therefore, has some TSH-like activity.
- Molar pregnancy or gestational trophoblastic neoplasm, a state in which hCG is often excessively elevated, may manifest as severe hyperthyroidism.
Etiology
- Graves ' disease is the leading cause of hyperthyroidism, accounting for approximately 95% of hyperthyroidism seen in pregnancy.
- Other causes similar to nonpregnant patients with the following exceptions:
- Transient gestational thyrotoxicosis
- A condition characterized by hyperthyroidism in first trimester and usually coexists with hyperemesis
- Not likely a disorder per se, but a result of excessive thyroidal stimulation from hCG
- May be difficult to distinguish from Graves ' disease. Differentiation assisted by lack of thyroid antibodies and thyrotoxic symptoms
- Increased risk with multiparity
- Trophoblastic disease as discussed earlier
- Postpartum thyroiditis
- A condition that may result in transient hyperthyroidism postpartum, much like subacute (de Quervain) thyroiditis
- Typically the initial hyperthyroid state goes unnoticed only to manifest itself as hypothyroidism in the period that follows.
Associated Conditions
- Hyperemesis gravidarum
- Trophoblastic disease or hydatidiform mole
- Preeclampsia
- Hypertension
Diagnosis
- Clinical presentation is similar to nonpregnant patients with the following exceptions:
- Weight loss may not be dramatic given weight increase with pregnancy.
- Maternal presentation is further complicated by fact that many signs and symptoms of hyperthyroidism are seen in normal pregnancy, such as:
- Heat intolerance
- Irritability
- Emotional lability
- Moist, warm skin
- Hyperreflexia
- Increased pulse rate
- Ophthalmopathy or goiter may suggest Graves ' disease even in pregnancy.
Tests
Lab
- TSH remains the mainstay of diagnosing hyperthyroidism in pregnancy; however, there are changes in thyroid function during pregnancy that may be misinterpreted for hyperthyroidism (1)[A].
- Increase in serum total thyroxine (T4) and triiodothyronine (T3)
- Caused by increased production of serum thyroxine-binding globulin (TBG) secondary to stimulatory effects of estrogen
- TSH is slightly suppressed in the first trimester.
- Free T4 and T3 are mildly increased but typically remain within the normal range.
- Abnormal TSH levels should be investigated further with free thyroid hormone levels.
- TSH receptor antibodies (TSHR-Ab)
- Obtain TSHR-Ab levels if Graves ' disease is suggested by clinical presentation or by thyroid function test (TFT) abnormalities (1)[C]
- TSHR-AB levels are important in assessing the likelihood for development of Fetal Graves ' Syndrome (see "Complications " ).
Imaging
- Radioactive iodine uptake (RAIU) test
- Contraindicated in pregnancy as the iodine can be taken up by the fetal thyroid and result in fetal thyroid ablation
- Fetal thyroid development begins typically at about 10 weeks gestation.
- If RAIU is inadvertently conducted prior to 10 weeks gestation, pregnant patients should be counseled that there is a high likelihood for normal fetal thyroid development.
Pathological Findings
Unchanged from nonpregnant patients. See "Hyperthyroidism " chapter.
Differential Diagnosis
- Anxiety
- Tachyarrhythmias
- Trophoblastic disease
- Pheochromocytoma
- Transient gestational thyrotoxicosis
- Normal pregnancy changes
- Subclinical hyperthyroidism (low TSH with normal free thyroid levels)
Treatment
- Hyperthyroidism in pregnancy is typically evaluated and treated on an outpatient basis.
- The following considerations should be made, however, in addressing more concerning features of this disease:
- Hyperemesis
- May coexist with hyperthyroidism
- Assess volume status
- IV fluids if indicated
- Symptomatic patients
- Beta-blockers and antithyroid drugs (ATDs) can be used in pregnant patients with significant symptoms (see "Medication " )
- Heart failure from uncontrolled hyperthyroidism
- Incidence may be increased in pregnant compared to nonpregnant patients.
- Management, however, does not differ between the 2 groups.
- Thyroid storm: Similar management as in nonpregnant with following modifications:
- Fetal monitoring
- If steroids are indicated, use steroids that cross placenta less readily (i.e., prednisone or methylprednisolone).
Preconception
- Patients with a history of hyperthyroidism should be advised to plan conception at a time of documented euthyroidism.
- Both hyperthyroidism and hypothyroidism implicated in adverse fetal outcomes.
- Patients who are planning to become pregnant who have recently had radioactive iodine thyroid ablation should consider deferring pregnancy for at least 6 months given the long half-life of these agents and their potential to affect fetal thyroid development.
Medication
- Polythiouracil (PTU) and methimazole may cross the placenta, cause suppression of the fetal thyroid, and result in fetal hypothyroidism or in fetal goiter.
- If used appropriately, however, ATDs do not appear to result in an adverse fetal outcome.
First Line
PTU (1)[B]
- Preferred ATD in pregnancy
- Use lowest dose possible to control maternal symptoms as may suppress fetal thyroid.
- Start with 50 mg PO t.i.d.
- Limit dose if possible to <300 mg/day
- Aim for free T4 levels in the upper limit of the normal range (2)[A]
- Mild maternal hyperthyroidism is preferred over hypothyroidism.
Second Line
Methimazole (Tapazole)
- Concern of increased fetal risk of scalp defects (aplasia cutis) and choanal/esophageal atresia
- These associations are weak if existent.
- May be used if the patient is allergic or intolerant of PTU
- Use lowest possible dose
- Start with 10 mg/day PO
- Limit dose if possible to <20 mg/day
Additional Treatment
General Measures
The overall goal is to keep the patient at the higher end of the euthyroid state throughout pregnancy with the lowest possible dose of ATDs.
Issues for Referral
- To obstetrician to evaluate for fetal goiter and neonatal hyperthyroidism
- To endocrinologist:
- Confusing or fluctuating TFTs
- Persistent symptoms despite ATD treatment
- Severe presenting symptoms such as thyroid storm or heart failure
- Patient with palpable thyroid nodule(s)
- To surgery if medical treatment unsuccessful
Additional Therapies
Radioactive iodine ablation is contraindicated in pregnancy as it can result in fetal thyroid ablation (2)[A].
Surgery
- Surgery may be indicated in those patients with severe hyperthyroidism not responsive to or intolerant of ATDs.
- If surgery is necessary, it is preferable to perform surgery in the second trimester when the risk of miscarriage or preterm labor may be less.
In-Patient Considerations
Admission Criteria
- Typically managed in an outpatient setting
- Admission is reserved for patients presenting with thyroid storm, heart failure, or for fetal indications.
Ongoing Care
Follow-Up Recommendations
- Breastfeeding
- PTU, methimazole, and beta-blockers other than atenolol are generally safe.
- Approximately 20 " 30% of the serum levels of atenolol are transmitted to breast milk.
- Radioactive iodine (2)[B]
- Postpartum women receiving radioactive iodine for either therapeutic or diagnostic reasons should delay breastfeeding.
- Timing of the resumption of breastfeeding depends on iodine formulation and dose.
- Technetium-99m and I-123 are preferred agents for thyroid scans in patients wishing to breastfeed.
- Patients are typically counseled to pump and discard their breast milk for 24 hours.
- I-131 is agent typically used in ablation
- Given the long half-life (8 days) and large dose used for ablation, breastfeeding should be deferred for several months.
- Treatment is generally delayed until after the infant has been weaned.
Patient Monitoring
- Monitor TSH and free T4 every 4 weeks
- Adjust ATD dose to keep the free T4 level in the high-normal to slightly elevated range
- Frequent monitoring is necessary as many women decrease or stop their ATDs later in pregnancy.
- ATD requirements often increase postpartum as Graves ' disease may flare during this period.
- Fetal monitoring with serial ultrasounds to assess tachycardia, goiter, growth, and hydropic changes may be necessary.
Diet
- Increased caloric intake may be necessary to offset the caloric deficit that occurs from a hypermetabolic state of pregnancy.
- Decreased sodium intake is advocated if hyperthyroidism is complicated by hypertension.
- Iodine requirements increase with pregnancy.
Prognosis
- Most maternal and fetal complications occur in patients with untreated hyperthyroidism.
- Graves ' disease typically improves in the third trimester, but may flare up postpartum.
Complications
- Maternal complications:
- Preeclampsia
- Congestive heart failure
- Arrhythmia
- Thyroid storm
- Fetal complications:
- Miscarriage
- IUGR or small-for-gestational age
- Prematurity
- Placental abruption
- Stillbirth
- Congenital malformations?
- Neonatal or fetal Graves ' hyperthyroidism
- Increased risk in mothers with untreated Graves ' disease and with high TSHR-Ab levels (>300%)
- May occur in asymptomatic mothers who have been treated for Graves ' disease in the past as persistent circulating TSHR-Abs may cross the placenta.
References
1 Thyroid disease in pregnancy. ACOG Practice Bulletin No. 37. Obstet Gynecol. 2002;100:387 " 396. [View Abstract]2Abolovich M, Amino N, Barbour LA. Management of thyroid dysfunction during pregnancy and postpartum: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2007;92:S1 " S47.
Additional Reading
1Mestman JH. Hyperthyroidism in pregnancy. Best Pract Res Clin Endocrinol Metab. 2004;18:267 " 288. [View Abstract]2Yang K, Burrow G. Thyroid disease. In: Lee RV, Rosene-Montella K, Barbour L, et al., eds. Medical care of the pregnant patient. Philadelphia, PA: American College of Physicians, 2000:276 " 283.
Codes
ICD9
- 242.80 Thyrotoxicosis of other specified origin without mention of thyrotoxic crisis or storm
- 242.90 Thyrotoxicosis without mention of goiter or other cause, and without mention of thyrotoxic crisis or storm
- 648.10 Thyroid dysfunction of mother, unspecified as to episode of care or not applicable
- 242.00 Toxic diffuse goiter without mention of thyrotoxic crisis or storm
- 242.10 Toxic uninodular goiter without mention of thyrotoxic crisis or storm
- 643.00 Mild hyperemesis gravidarum, unspecified as to episode of care or not applicable
- 775.3 Neonatal thyrotoxicosis
ICD10
- E05.80 Other thyrotoxicosis without thyrotoxic crisis or storm
- E05.90 Thyrotoxicosis, unsp without thyrotoxic crisis or storm
- O99.280 Endo, nutritional and metab diseases comp preg, unsp tri
- E05.00 Thyrotoxicosis w diffuse goiter w/o thyrotoxic crisis
- E05.10 Thyrotxcosis w toxic sing thyroid nodule w/o thyrotxc crisis
- P72.1 Transitory neonatal hyperthyroidism
SNOMED
- 237506002 thyrotoxicosis in pregnancy (disorder)
- 34486009 hyperthyroidism (disorder)
- 353295004 Graves ' disease (disorder)
- 14094001 excessive vomiting in pregnancy (disorder)
- 13795004 neonatal thyrotoxicosis (disorder)
- 199296002 endocrine, nutritional and metabolic disease complicating pregnancy, childbirth and puerperium (disorder)
Clinical Pearls
- The diagnosis of hyperthyroidism in pregnancy is complicated by:
- Overlap of hyperdynamic symptoms frequently seen in normal pregnancies
- Pregnancy-related changes in thyroid tests
- Untreated hyperthyroidism has been associated with adverse fetal outcomes.
- ATDs and beta-blockers are mainstay of treatment of Graves ' disease in pregnancy.
- Maternal symptom control is balanced against limiting the antithyroid effect on the fetus.
- Radioactive iodine is avoided in pregnancy, as it may result in fetal thyroid ablation.