#223 Thyroid Disease in Pregnancy Flashcards
How does maternal thyroid volume change during pregnancy?
Increases 10-30% during 3rd trimester, attributable to increases in extracellular fluid and blood volume during pregnancy
How does maternal total or bound thyroid hormone levels change in pregnancy?
Increases
How does maternal serum concentration of thyroid-binding globulin change during pregnancy?
Increases
How does the level of thyrotropin (AKA TSH) change in early pregnancy?
Decreases
Why does TSH decrease in early pregnancy?
Due to weak stimulation of TSH receptors by substantial quantities of hCG during first 12 weeks
What is the maternal status if TSH is decreased and Free T4 is Increased?
Overt hyperthyroidism
What is the maternal status if TSH is decreased and Free T4 has no change?
Subclinical hyperthyroidism
What is the maternal status if TSH is increased and Free T4 is decreased?
Overt hypothyroidism
What is the maternal status if TSH is increased and Free T4 has no change?
Subclinical hypothyroidism
How does the normal range of TSH change in late first trimester of pregnancy?
Lower limit reduced by 0.4mu/L and upper limit by 0.5mu/L.
How does the normal range of TSH change in 2nd trimester? Third?
No change, can use standard reference range
How does the reference range for total T4 and total T3 be changed after 16wks pregnancy?
Upper limit can be increased by 50%.
When does the fetal thyroid gland begin concentrating iodine and synthesizing thyroid hormone?
At approximately 12wks
Approximately what % of T4 in umbilical cord serum at delivery is maternal in origin?
30%
True or false, maternal T4 is important in normal fetal brain development
True
Regarding maternal thyroid disorder, what should be communicated to neonatologist/pediatrician?
Use of propylthiouracil, methimazole, hx of known maternal thyroid receptor antibodies (can affect neonatal thyroid function)
What % of pregnancies are complicated by hyperthyroidism?
0.2-0.7%
What % of hyperthyroidism cases in pregnancy are caused by Grave’s dx?
95%
What are the signs and symptoms of hyperthyroidism?
Nervousness, tremors, tachycardia, frequent stools, excessive sweating, heat intolerance, weight loss, goiter, insomnia, palpitations, HTN
What are distinctive features of Graves dx?
Ophthalmopathy (lid lag and lid retraction) and dermopathy (localized or pretibial myxedema)
What is inadequately treated maternal thyrotoxicosis associated with?
Greater risk of preeclampsia with SF, maternal heart failure, and thyroid storm
What is inadequately treated hyperthyroidism associated with in pregnancy?
Increase in medically indicated preterm deliveries, low birth weight, miscarriage, and stillbirth
How does fetal thyrotoxicosis typically manifest?
Fetal tachycardia and poor fetal growth
True or false, Graves disease can lead to neonatal hyper and hypothyroidism?
True. Thyroid stimulated immunoglobulin (neonate hyperthyroid) vs TSH-binding inhibitory immunoglobulins (neonate hypothyroid)
What % of neonates born to mothers with Graves dx will have hyperthyroidism or neonatal Graves dx?
1-5%
Subclinical hyperthyroidism is reported in what % of pregnant women?
0.8-1.7%
Is subclinical hyperthyroidism associated with adverse pregnancy outcomes?
No
Should you treat pregnant women with subclinical hyperthyroidism?
Not recommended, no benefit to mom or fetus
What # out of 1,000 pregnancies are complicated by overt hypothyroidism?
2-10 out of 1,000
What are common signs and symptoms of hypothyroidism?
Fatigue, constipation, cold intolerance, muscle cramps, and weight gain. Other clinical findings include edema, dry skin, hair loss, and a prolonged relaxation phase of deep tendon reflexes. Goiter may or may not be present
What is the most common cause of hypothyroidism in pregnancy?
Hashimoto thyroiditis
What characterizes Hashimoto thyroiditis (mechanism of disease)?
Glandular destruction by autoantibodies, particularly antithyroid peroxidase antibodies
What antibodies are associated with Hashimoto thyroiditis?
Antithyroid peroxidase antibodies
What is the recommended daily dietary intake of iodine in pregnant and lactating women?
220mcg in pregnant women. 290mcg in lactating women.
What adverse perinatal outcomes are associated with untreated overt hypothyroidism?
Spontaneous abortion, preeclampsia, preterm birth, abruptio placentae, stillbirth
True or false, adequate thyroid hormone replacement in overt hypothyroidism minimizes the risk of adverse outcomes?
True
What fetal and neonatal effects are associated with untreated maternal hypothyroidism?
Increased risk of low birth weight and impaired neuropsychologic development
What is the prevalence of fetal hypothyroidism in the offspring of women with Hashimoto thyroiditis (1 in how many)?
only 1 in 180,000
What is the prevalence (%) of subclinical hypothyroidism in pregnancy?
2-5%
Does treatment of subclinical hypothyroidism during pregnancy improve outcomes?
No evidence to support
Is universal screening for thyroid disease in pregnancy recommended?
No
When should you test a pregnant women for thyroid disorders?
Women with a personal or family hx of thyroid disease, type 1 DM, or clinical suspicion of thyroid disease.
What is the first line screening test to assess thyroid status in pregnancy?
TSH level
If TSH is elevated in pregnancy, what is the next test that should be done?
Free T4
If TSH is decreased in pregnancy, what is the next test that should be done?
Free T4 and total T3
Why measure total T3 rather than free T3?
Assays for estimating free T3 are less robust than those measuring free T4.
What value(s) should be monitored and used to dictate therapy in pregnant with with hyperthyroidism?
Adjust drug to achieve a free T4 at upper end of the normal pregnancy range. If also have T3 thyrotoxicosis, total T3 should be monitored with goal at upper end of normal pregnancy range.
What category of medication are propylthiouracil or methimazole?
Thioamides (treat hyperthyroidism)
What thioamide is typically avoided in first trimester and why?
Methimazole. Associated with rare embryopathy characterized by esophageal or choanal atresia as well as aplasia cutis
What medication is generally preferred for treatment of hyperthyroidism in first trimester?
Propylthiouracil
After first trimester, which medication should be used for hyperthyroidism?
Either methiazole or propylthiouracil. In rare cases, PTU results in clinically significant hepatotoxicity prompting transition.
What is a concern about transitioning from propylthiouracil to methimazole after first trimester?
A period of poor control of hyperthyroidism
What medication is preferred for T3-predominant thyrotoxicosis? Why?
Propylthiouracil, decreases T4 to T3 conversion
What is the conversion of propylthiouracil to methimazole?
Ratio of 20:1 PTU to methimazole
Transient leukopenia occurs in up to what % of pregnant women who take thioamide drugs? Does this require drug cessation?
10%. No.
What % of patients who take thioamide drugs get agranulocytosis? Does this require drug cessation?
Less than 1%. Yes.
Is development of agranulocytosis with thioamide drugs dose-related?
No
Should serial leukocyte counts be performed during thioamide administration?
No. Agranulocytosis is acute onset so serial leukocyte counts during therapy are not helpful
What is the dosage of propylthiouracil?
100-600mg daily, divided into three doses, PO. Typical dose is 200-400mg daily.
What is the dosage of methimazole?
5-30mg orally daily, divided into two doses (may be reduced to one daily dose as maintenance therapy is established)
What medication is preferred for symptomatic palpitations in pregnant patients with hyperthyroidism? What dosing?
Propranolol. 10-40mg taken 3-4x/daily
What is the recommendation for initial dose of T4 in pregnancy?
1-2mcg/kg daily (approximately 100mcg daily), may require larger doses if prior thyroidectomy or radioiodine therapy
What lab value guides treatment of hypothyroidism in pregnancy?
TSH value
What is the goal TSH level when treating hypothyroidism in pregnancy?
TSH goal between lower limit of reference range and 2.5mu/L.
How often should TSH be evaluated while adjusting thyroid hormone medication?
Every 4-6wks
Should thyroid hormone medication be adjusted in early pregnancy?
Can do anticipatory 25% increases in T4 replacement at pregnancy confirmation
What % of reproductive-aged women will have autoantibodies to thyroid peroxidase and thyroglobulin?
Up to 20%. Most test euthyroid
Transient biochemical features of hyperthyroidism may be observed in what % of women in early pregnancy?
3-11%
What are causes of gestational transient hyperthyroidism (aka physiologic hyperthyroidism)?
Multiple gestation or molar pregnancy, for example
Are women with gestational transient hyperthyroidism typical symptomatic?
No
Do women with gestational transient hyperthyroidism require treatment?
Not been shown to be beneficial, not recommended. Not associated with poor pregnancy outcomes.
Are measurements of thyroid function recommended for patients with hyperemesis gravidarum?
Not unless other signs of overt hyperthyroidism are evident
How does thyroid storm typically manifest?
Combination of the following signs and symptoms: fever, tachycardia, cardiac dysrhythmia, and CNS dysfunction
Is thyroid storm or cardiomyopathy from hyperthyroidism more common in pregnancy?
Cardiomyopathy
What % of pregnant women with uncontrolled hyperthyroidism develop heart failure and pulmonary HTN from cardiomyopathy d/t excessive T4?
9%
True or false, T4-induced cardiomyopathy and pulmonary HTN are reversible?
True
If thyroid storm or thyrotoxic heart failure is suspected, what lab values should be checked?
Serum free T4, total T3, and TSH levels
What is the medical management of thyroid storm or thyrotoxic heart failure in pregnancy?
- Inhibit thyroid release of T3 and T4 (PTU 1000mg PO then 200mg q6h); iodine administration 1-2h after pTU.
- Further block peripheral conversion of T4 to T3 (dexamethasone or hydrocortisone)
- Propanolol, labetalol, or esmolol (caution in setting of heart failure)
- Supportive measures as needed
When should a diagnosis of fetal thyrotoxicosis be considered in cases of maternal hyperthyroidism?
Fetal hydrops, growth restriction, fetal goiter, or persistent fetal tachycardia
Thyroid nodules are found in what % of reproductive-aged women?
1-2%, with prevalence increasing with age
What is the initial work up of a pregnant woman with a thyroid nodule?
Complete H&P, serum TSH testing, ultrasound of the neck
What % of solitary thyroid nodules are benign?
90-95%
What ultrasound characteristics of thyroid nodules are associated with malignancy?
Hypoechoic pattern, irregular margins, and microcalcifications. When all 3 present, these features correlate with a malignancy risk exceeding 70%
If thyroid nodule in pregnancy concerning for possible malignancy, what is the next step?
Fine-needle aspiration
Is radioiodine scanning in pregnancy allowed?
Not recommended because of theoretical risk associated with fetal irradiation
What is typical management for a women with thyroid cancer diagnosed in 1st or 2nd trimester?
Thyroidectomy may be performed before 3rd trimester, but concerning for inadvertent removal of parathyroid glands often leads to delay postpartum.
What is the typical management for a women with thyroid cancer diagnosed in 3rd trimester?
Deferred to immediate postpartum period
How is postpartum thyroiditis defined?
Thyroid dysfunction within 12 months of delivery (hyper, hypo, or both)
Transient autoimmune thyroiditis is found in what % of women during first year after childbirth?
5-10%
What are the two clinical phases in classical postpartum thyroiditis?
New-onset abnormal TSH and free T4
- Destruction-induced thyrotoxicosis (small, painless goiter) usually lasts few months
- Overt hypothyroidism that occurs between 4-8 months postpartum and thyromegaly
What are the outcomes of postpartum thyroiditis?
Most resolve spontaneously. Approximately 1/3 will eventually develop permanent, overt hypothyroidism. Annual progression rate is 3.6%
True or false, presence of thyroid autoantibodies increases the risk of women with postpartum thyroiditis developing permanent hypothyroidism
True
