MFM Clinical Guideline Thyroid Disease in Pregnancy Thyroid disease is the 2nd most common endocrinopathy in pregnancy after diabetes. In pregnancy: thyroid volume ↑ 30%, total/bound T3 and T4 levels ↑, but free/unbound T3 and T4 levels are stable due to ↑ thyroid binding globulin. In the 1st trimester, TSH levels ↓ due to high levels of hCG,which directly stimulates the TSH receptor, but return to baseline in the 2nd trimester. TSH does not cross the placenta. Maternal T4 is transferred to the fetus and is important for fetal brain development, especially before the fetal thyroid gland begins to synthesize thyroid hormone at 12-14 weeks. Screening for Thyroid Disease in Pregnancy Table 1: Screening. Table 2: Pregnancy reference ranges. Who to Screen Trimester TSH FT4* Age > 30 1st 0.1 - 2.5 0.8 - 1.2 BMI > 40 mIU/L ng/dL Current signs/symptoms of thyroid dysfunction 2nd 0.2 - 3 mIU/L 0.6 - 1 ng/dL Known positive thyroid antibodies 3rd 0.3 - 3 mIU/L 0.5 - 0.8 ng.dL Goiter *Due to inaccuracy of thyroid testing in pregnancy, Hx head/neck irradiation or thyroid surgery FT4 goal FHx thyroid disease should be the upper half of the reference range Pregestational diabetes Table 3: Interpreting the results. Autoimmune disorders TSH FT4 Hx of pregnancy loss, PTD, infertility Use of amiodarone or lithium, recent administration of Overt Hyperthyroidism ↓ ↑ iodinated radiologic contrast Subclinical ↓ NL Hyperthyroidism Residing in an area of known iodine deficiency Gestational 1st trim: ↓ UL How to Screen Hyperthyroidism 2nd trim: NL/ Step 1: TSH, FT4 NL slight ↑ Step 2 (TSH ↑): TPO antibodies Step 2 (TSH ↓): FT3, thyroid stimulating immunoglobulin Overt Hypothyroidism ↑ ↓ (TSI)* Subclinical Hypothyroidism ↑ NL *TSI is a type of thyrotropin receptor antibody (TRaB) Isolated Hypothyroxinemia NL ↓ Hypothyroidism in Pregnancy Thyroid peroxidase (TPO) antibodies - ↑ in 90% cases of Hashimoto's, can be seen in low concentration in euthyroidism and Graves; 2-17% of all pregnant women will be positive for either TPO or Tg antibodies; TPO antibodies are able to cross the placenta, however, they are not associated w/ fetal thyroid dysfunction Associations: ↑ risk of spontaneous pregnancy loss Unclear associations: recurrent pregnancy loss, PTD, perinatal death, placental abruption, postpartum depression, neonatal RDS Management: o TPO+, euthyroid: TSH q trimester . May be at risk of hypothyroidism due to the stress of pregnancy as the ability of the thyroid to augment hormone production is compromised MFM Clinical Guideline o TPO+, euthyroid, RPL 2 ongoing RCTs are attempting to address if treatment to newly pregnant euthyroid women w/ TPO decreases loss; ATA guidelines state that treatment w/ levothyroxine (25-50 mcg) may be considered given its potential benefits; if treating or if REI has started treatment, discontinue treatment in the 2nd trimester and check TSH in 4-6 wks, again in the 3rd trimester, and again approx 3 months postpartum w/ a PCP/endocrinologist Overt Hypothyroidism Incidence: 2 - 10 / 1,000 pregnancies o Associated w/ T1 DM (20-30%), Addison’s disease, pernicious anemia, myasthenia gravis Signs & symptoms: fatigue, constipation, cold intolerance, muscle cramps, weight gain, edema, dry skin, hair loss, prolonged relaxation phase of DTR, goiter, vision changes, mood imbalances Diagnosis: ↑ TSH, ↓ FT4 Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common cause in areas w/o iodine deficiency and is characterized by glandular destruction by autoantibodies (esp. TPO) Adverse pregnancy outcomes (poor control): miscarriage/IUFD, PTD, preeclampsia, abruption Adverse fetal/neonatal outcomes (poor control): LBW, impaired neuropsychological development, rarely hypothyroidism (1/180,000 offspring in women w/ Hashimoto's) Preconception management: o Maintain TSH < 2.5 for those planning pregnancy Pregnancy Management: o Initiating treatment: levothyroxine (Synthroid, Levoxyl, Thyroxine, Levothyroid, Tirosint (gel capsule, can be helpful w/ hx bariatric surgery or malabsorptive diseases )) contains only T4, initiate at 1-2 mcg/kg/day (approx ~ 100 mcg), take on an empty stomach w/ no food or meds for 30 - 60 min afterwards (see table below) o Ongoing treatment: as soon as patient finds out she is pregnant, increase weekly dose by 2 additional pills (9 pills/wk) or ↑ daily dose by 20-30% (compensates for the 20-30% ↑ requirement of most pregnant women) and order initial labs, make subsequent adjustments as needed o Other preparations: should ideally not be started in pregnancy, but may be continued in those well controlled before pregnancy . Cytomel, Triostat, Liothyronine - contain only T3, may be required for symptomatic relief in those w/ T4 replacement and ↓ T3 . Natural/dessicated thyroid (Armour Thyroid) - contain both T3/T4, derived from porcine thyroid glands . Supplements: some patients may be on additional supplements to optimize conversion of T4 → T3 and are safe to continue Zinc - 30 - 60 mg QD in divided doses, don’t take w/ thyroid meds Selenium - 200 - 400 mg QD in divided doses, don’t take w/ thyroid meds o Dose adjustments: repeat TSH q 4 - 6 weeks and adjust dosing in 20-30% increments (typically 25 - 50 mcg) to keep TSH w/in trimester specific ranges o Fetal surveillance: none is needed in women who are euthyroid w/ treatment; consider surveillance starting at 34 wks for those who are poorly controlled Postpartum management: o Those being treated before pregnancy: if euthyroid on a stable dose before pregnancy, restart levothyroxine at prepregnancy dose and check TSH at the postpartum visit or if excessive weight gain ↓ dose by 20-30% and check TSH at the postpartum visit o Those initiating treatment in pregnancy: ↓ dose by 20-30% and check TSH at the postpartum visit or if on a very low dose, may consider d/c at delivery and check TSH at the postpartum visit MFM Clinical Guideline Subclinical Hypothyroidism Incidence: 2-5% of pregnancies Diagnosis: ↑ TSH, NL FT4 Adverse pregnancy outcomes: studies are conflicting and there is no evidence that treatment improves pregnancy outcomes Adverse fetal/neonatal outcomes: 2 cohort studies in 1999 suggested that untreated subclinical hypothyroidism may lead to adverse neurodevelopmental outcomes in offspring 2012 Controlled Antenatal Thyroid Screening (CATS) Study and 2017 MFMU study (RCTs) showed no difference in neurodevelopment in offspring in treated vs. untreated women at 3 year and 5 year follow up o Advocates who support the 2017 ATA guidelines, criticise that levothyroxine wasn’t started until an average of 13 (CATS) to 17 weeks (MFMU), MFMU subgroup analysis for < 14 wks was not powered for this outcome, and that earlier treatment may lead to improved outcomes Management: o 1st trimester diagnosis: consider treatment w/ 50 mcg levothyroxine and following the above management of overt hypothyroidism; counsel that it is not yet known if treatment in the 1st trimester improves neurologic outcomes in offspring o 2nd/3rd trimester diagnosis: treatment is not recommended as it has not been shown to improve outcomes in the above RCTs Euthyroid Women s/p Thyroidectomy or Ablation: Management: TSH every 4-6 weeks initially, may space out to 6-8 weeks when stable Isolated Hypothyroxinemia Diagnosis: NL TSH, ↓ FT4 Management: treatment is not recommended, no follow up is required Hyperthyroidism in Pregnancy Thyroid stimulating immunoglobulin (TSI) - a type of Thyrotropin/TSH receptor antibodies (TRAb) - ↑ in 95% of active Graves Disease (GD) and may remain high following ablation or surgery Can cross the placenta and cause either fetal hyperthyroidism or hypothyroidism o 1-5% will develop neonatal GD caused by transplacental passage of TSI, especially in those who aren’t adequately treated or have had a thyroidectomy Generally ↓ as pregnancy progresses Check w/ initial labs and again at 28-32 weeks on all hyperthyroid patients and those w/ a hx of GD treated w/ surgery/ablation Gestational/transient Hyperthyroidism Incidence: 1-3% of pregnancies, hCG typically peaks at 7-11 weeks and should return to normal by 14-18 weeks Diagnosis: ↓ TSH, FT4 that normalizes in the 2nd half of pregnancy Associated with: hyperemesis gravidarum, multiple gestations, and molar pregnancy Gestational or true hyperthyroidism?: no hx of thyroid disease and no clinical signs of hyperthyroidism suggests gestational o TSH should normalize in the 2nd trimester o TSI can help if unclear (should be + in Graves) MFM Clinical Guideline Management: treatment w/ thioamides is not recommended, treat w/ beta blockers for symptomatic relief PRN, if there are palpable thyroid nodules, needs an u/s and FT3 to check for T3 toxicosis Follow up: repeat labs in the 2nd trimester Overt Hyperthyroidism Incidence: 0.2% of pregnancies o 95%: Grave’s disease o 5%: toxic multinodular goiter, toxic adenoma, factitious thyrotoxicosis (meds) o Rare: struma ovarii (teratoma containing thyroid tissue) Diagnosis: ↓ TSH, ↑ FT4 (rarely ↑ FT3 in T3 toxicosis from multinodular goiter) Signs & symptoms: nervousness, tremors, tachycardia, frequent stools, sweating, heat intolerance, weight loss, goiter, dysphagia, insomnia, palpitation, acute/labile hypertension o Graves: ophthalmopathy localized or pretibial myxedema Adverse pregnancy outcomes: preeclampsia, maternal heart failure Adverse fetal/neonatal outcomes: ↑ medically indicated PTD, LBW, fetal loss, hydrops, IUGR, goiter, tachycardia o Neonates are usually euthyroid o Antibodies can cross the placenta and causing immune