Basics
Description
- Complex hormonal and metabolic changes occur during pregnancy that affect thyroid function and result in increased thyroid hormone demand and production.
- Increased production of thyroid hormone may be compromised in pregnant women with preexisting hypothyroidism.
- Maintaining euthymic state is important in pregnancy as maternal thyroid hormone deficiency is associated with adverse fetal outcomes and impaired intellectual development in children.
Epidemiology
- Thyroid disease is common in women; 5 " 10x more common in women than in men.
- Primary hypothyroidism is most likely to manifest itself between the ages of 40 and 60 but is often seen in women of childbearing years.
Prevalence
- 1 " 2% of women who become pregnant are already receiving thyroxine therapy for hypothyroidism.
- 2% of women may enter pregnancy with subclinical, undiagnosed hypothyroidism.
- Postpartum thyroiditis affects approximately 5 " 9% of women in the postpartum period.
Risk Factors
- Women already on thyroxine or with a history of hypothyroidism
- History of postpartum thyroiditis
- Those who have type I diabetes or other autoimmune disorders
- Family history of autoimmune thyroiditis or other autoimmune diseases
- Past history of neck irradiation, thyroid ablation, or thyroidectomy
- Women with a goiter
Genetics
- The disease clusters in families with concordance rate approaching 40 " 50% in monozygotic twins.
- HLA-DR3 and HLA-DR4 linked to Hashimoto 's
- HLA-DR5 linked to postpartum thyroiditis
General Prevention
- No current recommendations for universal screening of all women before or during pregnancy
- The Endocrine Society and ACOG, however, recommend screening TSH in women belonging to high-risk groups or with symptoms suggestive of hypothyroidism (see "Risk Factors " ) (1)[B].
- Screening should occur, preferably, prior to pregnancy or in early gestation.
Pathophysiology
- Similar to the nonpregnant population
- Most common cause of primary hypothyroidism in women of childbearing age is immune-mediated destruction of the thyroid gland.
Etiology
- Hashimoto 's thyroiditis
- Main cause of hypothyroidism in pregnant and nonpregnant women
- May also flare postpartum like many other autoimmune diseases
- Otherwise, causes are the same in pregnant women with the following exceptions:
- Iodine deficiency
- Rare cause of hypothyroidism in the US both during and outside of pregnancy
- Incidence in the US and third world countries is believed to increase during pregnancy due to increased urinary iodine secretion and fetal uptake of iodine.
- Postpartum thyroiditis
- Can also contribute to hypothyroidism
- Autoimmune-mediated inflammation of thyroid resulting in period of hyper-thyroidism followed by a period of hypo-thyroidism, which may be self-limited
- Period of hyperthyroidism often not diagnosed
- Features of hypothyroidism typically present >3 months postpartum, with peak incidence at about 5 months postpartum.
- Women who develop postpartum thyroiditis are at high risk of developing permanent hypothyroidism in subsequent 5 " 10 years.
Associated Conditions
- Other autoimmune disorders
- Diabetes mellitus
- Idiopathic adrenal insufficiency
- Hypoparathyroidism
- Myasthenia gravis
- Vitiligo
- Possible increased risk of preeclampsia
Diagnosis
Management of hypothyroidism in pregnancy is typically done on an outpatient basis.
History
- Clinical presentation similar to nonpregnant patients
- However, presentation is complicated by the fact that many signs and symptoms of hypothyroidism are also seen in normal pregnancy, such as:
- Fatigue or lethargy
- Constipation
- Muscle cramps and arthralgia
- Carpal tunnel syndrome
- Weight gain
- Dry skin
- Puffiness/edema
Physical Exam
- Thyroid gland may be mildly enlarged with normal pregnancy although this should not be notable on palpation.
- Mild goiter may be seen during pregnancy in regions where iodine intake is low.
- Significant thyroid growth in pregnancy should prompt further evaluation.
- Other exam findings suggestive of hypothyroidism are similar in pregnancy to that seen in nonpregnant patients.
Tests
Lab
- TSH remains the mainstay of diagnosing hypothyroidism in pregnancy (2)[A].
- However, there are major changes in thyroid function during pregnancy that may make interpretation of these results difficult:
- Serum thyroxine-binding globulin (TBG)
- Production increases due to estrogen effect leading to an increase in serum total thyroxine (T4) and triiodothyronine (T3).
- TBG excess in pregnancy results in a low T3- resin uptake.
- Serum TSH
- Transiently low in the first trimester
- Therefore, borderline high TSH during this time in pregnancy may actually represent a hypothyroid state.
- Some authorities have proposed using gestational age-specific nomograms for TSH (3)[C].
- Free T4 and T3
- Mildly increased but typically remain within the normal range
- Free T4 index is also still accurate.
- Screening for hypothyroidism should still be initiated by checking TSH.
- If the TSH is abnormal or suspicion remains for hypothyroidism, then free T4 of free T4 index should be checked.
- Checking antithyroid peroxidase antibodies and/or antithyroglobulin antibodies, although not standardized practice, may be helpful in diagnosing autoimmune thyroiditis such as Hashimoto 's or postpartum thyroiditis (2)[C].
- These antibodies have also been implicated in an increased miscarriage rate.
- Subclinical hypothyroidism
- Asymptomatic women with elevated TSH but free T4 within the reference range
- Prevalence may be as high as 5%
- (see "Treatment " )
- Mothers treated for Graves ' disease with thyroid ablation in the past may still have circulating thyroid antibodies which may cross the placenta and result in neonatal Graves ' disease.
- These mothers should have thyroid-stimulating immunoglobulins checked as high titers have been implicated in increasing the risk of neonatal Graves ' disease.
Pathological Findings
Unchanged from the nonpregnant patient. See "Hypothyroidism " chapter.
Differential Diagnosis
- Anxiety
- Depression
- Postpartum thyroiditis may be confused with postpartum depression.
- Systemic diseases
- Congestive heart failure
- Nephrotic syndrome
- Hepatic failure
Treatment
- Patients who have documented hypothyroidism should be advised to plan conception at a time of documented euthyroidism.
- Consider increasing dose of levothyroxine at the time of conception even prior to initial evaluation and laboratory testing (4)[C].
- Recommendation based on increased thyroxine requirements noted to occur as early as 5th week of gestation as well as importance of thyroid hormone on fetal brain development, an important process in early gestation.
- This should be considered particularly in those patients who have had thyroid ablation or total thyroidectomy as they are the least able to increase thyroid hormone production.
- Debate ongoing about whether to treat subclinical hypothyroidism.
- Reports of associated impaired neurodevelopment in offspring
- However, no evidence that treatment improves fetal outcomes.
- The Endocrine Society advocates thyroid replacement though evidence is poor.
Medication
Levothyroxine (Synthroid, Levothroid)
- Dose
- Starting dose 1.0 " 2.0 ¼g/kg/day
- Increase by 25 " 50 ¼g every 4 " 6 weeks until TSH normalizes
- Patients should stay on the same brand of medication throughout pregnancy to avoid agent-specific variation in bio-availability.
- Transplacental transfer of levothyroxine negligible and has not been associated with birth defects, the rate of which may be increased in fetuses with hypothyroidism.
- Significant possible interactions
- Prenatal vitamins and ferrous sulfate may decrease the absorption of levothyroxine when taken together.
- Patients should be counseled to take these medications at separate times during day.
Additional Treatment
General Measures
Restore euthyroid state
Issues for Referral
- If neonatal Graves ' disease is confirmed or suspected, then referral to maternal fetal medicine (MFM) or neonatology may be warranted.
- Reason to refer to endocrinologist:
- Confusing or fluctuating thyroid function test (TFTs)
- Hypothyroidism persisting despite increasing levothyroxine dosing
- Central hypothyroidism implicated as cause of hypothyroidism
- Patient presents with myxedema coma
- Thyroid nodule palpated on exam
New thyroid nodules in pregnancy should be aggressively investigated because of the high incidence of malignancy (2)[C].
Complementary and Alternative Medicine
Use of unregulated thyroid replacement not recommended in pregnancy because of critical nature of supplying exact thyroid dose in these patients
In-Patient Considerations
Admission Criteria
- Typically managed in an outpatient setting
- Admission criteria same for pregnant patients, particularly if presenting with myxedema coma
- Management during labor is unchanged except need for neonatal testing in mothers previously treated with thyroid ablation for Graves ' disease.
Ongoing Care
Follow-Up Recommendations
Patient Monitoring
- Check TSH 6 " 8 weeks after conception
- Check TSH at least once every trimester
- Some clinicians may monitor TSH more frequently, as often as monthly, particularly following an adjustment in levothyroxine dose or if there have been significant TSH fluctuations.
- Many experts aim to keep the TSH in midrange of normal as hyperthyroidism may also result in adverse fetal outcomes.
Diet
High-fiber diet if constipation is significant
Prognosis
- Thyroid hormone requirements typically increase with pregnancy and may increase by as much as 50%.
- Hypothyroid patients with poor reserve may not be able to generate the amount of thyroid hormone necessary for maternal and fetal well-being without further supplementation.
- Incidence of fetal complications that result from hypothyroidism is minimized in adequately treated, euthymic mothers.
Complications
- Women with untreated hypothyroidism may not be able to conceive as it can result in anovulation.
- Complications to mother are similar to those outside of pregnancy except for an increased risk of preeclampsia.
- Potential fetal complications include:
- Spontaneous abortion
- Fetal loss
- Low birth weight
- Neuropsychological impairment
- Congenital hypothyroidism
- Congenital anomalies
- Breastfeeding is safe in mothers on levothyroxine.
- Small amount of this drug is excreted into breast milk but at too low of a concentration to cause neonatal concerns.
- Infants with congenital hypothyroidism may actually benefit from the low level of thyroxine found in the breast milk of mothers on levothyroxine.
References
1Abalovich M, Amino N, Barbour LA. Management of thyroid dysfunction during pregnancy and postpartum. J Clin Endocrinol Metab. 2007;92:S1 " S47. [View Abstract]2 Thyroid disease in pregnancy. ACOG Practice Bulletin No. 37. Obstet Gynecol. 2002;100:387 " 396. [View Abstract]3Casey BM, Leveno KJ. Thyroid disease in pregnancy. Obstet Gynecol. 2006;108:1283 " 1292. [View Abstract]4Haddow J, Palomaki GE, Allan WC. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549 " 555. [View Abstract]
Additional Reading
1Fitzpatrick DL, Russell MA. Diagnosis and management of thyroid disease in pregnancy. Obstet Gynecol Clin N Am. 2010;37:173 " 193. [View Abstract]
Codes
ICD9
- 244.8 Other specified acquired hypothyroidism
- 244.9 Unspecified hypothyroidism
- 648.90 Other current conditions classifiable elsewhere of mother, unspecified as to episode of care or not applicable
- 648.14 Thyroid dysfunction of mother, postpartum condition or complication
ICD10
- E03.8 Other specified hypothyroidism
- E03.9 Hypothyroidism, unspecified
- O99.280 Endo, nutritional and metab diseases comp preg, unsp tri
- O90.5 Postpartum thyroiditis
SNOMED
- 40930008 hypothyroidism (disorder)
- 199296002 endocrine, nutritional and metabolic disease complicating pregnancy, childbirth and puerperium (disorder)
- 111566002 acquired hypothyroidism (disorder)
- 52772002 postpartum thyroiditis (disorder)
Clinical Pearls
- Untreated hypothyroidism in pregnancy may result in adverse fetal outcome and has been linked to impaired intellectual development in children.
- Diagnosis of hypothyroidism in pregnancy is complicated by the difficulty in distinguishing signs and symptoms suggestive of hypothyroidism from normal pregnancy.
- Postpartum thyroiditis is a disorder that is unique to pregnancy in which postpartum hypothyroidism may result from an autoimmune-mediated destruction of the thyroid gland.