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Pregnancy & Thyroid
Zohreh Moosavi
Associate professor of Endocriology
Imam Reza General Hospital
Mashad University
Imam Reza weeky Conferance
Objectives
Thyroid Disorders & Pregnancy Normal thyroid phsyiology & pregnancy
Hypothyroidism & pregnancy
Thyrotoxicosis & pregnancy
Postpartum thyroid dysfunction
Thyroid adaptation during
normal pregnancy
Change in thyroid physiology
Change in thyroid function tests
Thyroid physiology
Increase in thyroxine binding globulin
Stimulation of the TSH receptor by HCG
Thyroid Disease Spectrum
0 10 5
TSH, IU/mL
Subclinical Hypothyroidism
TSH >2.5 IU/mL, Free T4 Normal
Overt Hypothyroidism
TSH >10 IU/mL, Free T4 Low
Euthyroid
TSH 0.4-4 IU/mL, Free T4 Normal
Hyperthyroidism
TSH <0.2 IU/mL, Free T3/T4 Normal or Elevated
.
Healthy pregnant women
TSH = 0.03 to 0.1 mu/L
Trimester – specific TSH
First trimester 0.1- 2.5
Second 0.2- 3
Third 0.3- 3
Hypothyroidism
Overt Hypothyroidism
elevated TSH, reduced free T4
Subclinical Hypothyroidism
elevated TSH, normal free T4
Levothyroxine o.1 mg=100mcg
Euthyrex 100 mcg, 50 mcg
Thyroid & Pregnancy: Hypothyroidism
85% will need increase in LT4 dose during pregnancy due
to increased TBG levels (ave dose increase 48%)
Risks:
increased spont abort, HTN/preeclampsia, abruption, anemia,
postpartum hemorrhage, preterm labour, baby SGA
Fetal neuropsychological development (NEJM, 341(8):549-555, Aug
31, 2001):
– Cognitive testing of children age 7-9
– Untreated hyothyroid mothers vs. normal mothers:
• Average of 7 IQ points less in children
• Increased risk of IQ < 85 (19% vs. 5%)
– Retrospective study, data-dredging?
Thyroid peroxidase antibodies
Anti TPO
LT4 dose adjustment in Pregnancy: - Optimize TSH preconception (0.4 – 2.5 mU/L)
- TSH at pregnancy diagnosis (~3-4 wk gestation), q1mos during 1st 20
wks and after any LT4 dose change, q2mos 20 wks to term
- Instruct women to take 2 extra thyroid pills/wk (q Mon, Thurs) for 29%
dose increase once pregnancy suspected (+ commercial preg test)
- If starting LT4 during preg: initial dose 2 ug/kg/d and recheck TSH q4wk
until euthythyroid
TSH Dose Adjustment
TSH increased but < 10 Increase dose by 50 ug/d
TSH 10-20 Increase dose by 50-75 ug/d
TSH > 20 Increase dose by 100 ug/d
Goiter and Thyroid Nodules
Hyperthyroidism
Overt Hyperthyroidism
elevated free T4 and/ or free T3, Low TSH
Subclinical Hyperthyroidism
normal free T4, Low TSH
Thyrotoxicosis & Pregnancy
Causes: Graves’ disease
TMNG, toxic adenoma
Thyroiditis
Hydatiform mole
Gestational hCG-asscociated Thyrotoxicosis
• Hyperemesis gravidarum hCG
• 60% TSH, 50% FT4
• Resolves by 20 wks gestation
• Only Rx with ATD if persists > 20 wk
Graves Disease
hCG-mediated (gestational transient thyrotoxicosis )
Indication for treatment
Therapeutic options
Goals of antithyroid drug therapy
Thyroid & Pregnancy: Normal Physiology
Fetal thyroid starts working at 12-14 wks
T4 & T3 cross placenta but do so minimally
Cross placenta well:
MTZ > PTU
TSH-R Ab (stim or block)
ATD (PTU & MTZ):
Fetal goitre (can compress trachea after birth)
MTZ aplasia cutis scalp defects
Other MTZ reported embryopathy: choanal atresia, esophageal
atresia, tracheo-esophageal fistula
Therefore do NOT use MTZ during pregnancy, use PTU instead
A good fetal outcome:
Free T4 high normal range
Lowest drug dose
Propylthiouracil ( PTU )
Methimazole
Beta blockers
Dose and Monitoring
T4 ( total ) 14-18 mcg/dl
TSH low normal
TSH
Low High
FT4 FT4 & FT3
Low
1° Hypothyroid
Low
Central
Hypothyroid
TRH Stim.
If
equivocal
MRI, etc.
High
1° Thyrotoxicosis
High
2° thyrotoxicosis
•Endo consult
•FT3, rT3
•MRI, α-SU
RAIU
Thyroid & Pregnancy: Normal Physiology
Increased estrogen increased TBG (peaks wk 15-20)
Higher total T4 & T3:
normal FT4 & FT3 if normal thyroid fn. and good assay
many automated FT4 assays underestimate true FT4 level (except
Nichols equilibrium dialysis free T4 assay)
if suspect your local FT4 assay is underestimating FT4 can check
total T4 & T3 instead (normal pregnant range ~ 1.5x
nonpregnant)
hCG peak end of 1st trimester, hCG has weak TSH agonist
effect so may cause:
slight goitre
mild TSH suppression (0.1-0.4 mU/L) in 9% of preg
mild FT4 rise in 14% of preg
No TSH & FTI at end of 1st trimester
as expected from hCG effect
Requirement to increase LT4 dose
occurred between weeks 4 -20
Despite exponential rise in estradiol
throughout pregnancy (note y-axis
units) TBG levels plateau at 20 wks
• LT4 dose requirement tied to rising TBG levels
(THBI inversely proportional to TBG level)
• By 10 wks need average increase of 29% LT4 dose
• By 20 wks need average increase of 48% LT4 dose
• No increase of dose beyond 20 wks required
* Regardless of cause of hypothyroidism (Hashimoto’s,
thyroidectomy) initial LT4 dose increase is usually
required early (~ week 8), before 1st prenatal visit!
Pregnancy: screen for thyroid dysfn ?
Universal screening not currently recommended: ACOG, AACE, Endo Society, ATA
Controversial!
Definitely screen: Goitre, FHx thyroid dysfn., prior postpartum thyroiditis,
T1DM
Ideally, check TSH preconception: 2.5-5.0 mU/L: recheck TSH during 1st trimester
0.4-2.5 mU/L: do not need to recheck during preg
If TSH not done preconception do at earliest prenatal visit:
0.1-0.4 mU/L: hCG effect (9% preg), recheck in 5wk
< 0.1 mU/L: recheck immediately with FT4, FT3, T4, T3
Thyrotoxicosis & Pregnancy
Risks: Maternal: stillbirth, preterm labor, preeclampsia,
CHF, thyroid storm during labor
Fetal: SGA, possibly congenital malformation (if 1st
trimester thyrotoxicosis), fetal tachycardia, hydrops
fetalis, neonatal thyrotoxicosis
Thyrotoxicosis & Pregnancy
Diagnosis difficult: hCG effect:
• Suppressed TSH (9%) +/- FT4 (14%) until 12 wks
• Enhanced if hyperemesis gravidarum: 50-60% with abnormal TSH & FT4, duration to 20 wks
FT4 assays reading falsely low
T4 elevated due to TBG (1.5x normal)
NO RADIOIODINE
Measure: TSH, FT4, FT3, T4, T3, thyroid antibodies?
Examine: goitre? orbitopathy? pretibial myxedema?
Pregnant & Suppressed TSH
TSH < 0.1 TSH 0.1 – 0.4
Recheck in 5 wks
FT4, FT3, T4, T3
Thyroid Ab’s
Examine
Normalizes Still suppressed
• Very High TFT’s:
• TSH undetectable
• very high free/total T4/T3
• hyperthyroid symptoms
• no hyperemesis
• TSH-R ab +
• orbitopathy
• goitre, nodule/TMNG
• pretibial myxedema
Treat Hyperthyroidism (PTU)
Hyperemesis Gravidarum
Abnormal TFT’s past 20 wk
Don’t treat with PTU
Case 1
31 year old female
G2P1A0, 11 weeks pregnant
Well except fatigue
Hb 108, ferritin 7 (Fe and LT4 interaction?)
TSH 0.2 mU/L, FT4 7 pM
Started on LT4 0.05 TSH < 0.01 mU/L
FT4 12 pM, FT3 2.1 pM
Thyrotoxicosis & Pregnancy: Rx
No RAI ever (destroy fetal thyroid)
PTU Start 100 mg tid, titrate to lowest possible dose
Monitor qmos on Rx: T4, T3, FT4, FT3
– TSH less useful (lags, hCG suppression)
Aim for high-normal to slightly elevated hormone levels
– T4 150-230 nM, T3 3.8-4.6 nM, FT4 26-32 pM
3rd trimester: titrate PTU down & d/c prior to delivery if TFT’s permit to minimize risk of fetal goitre
Consider fetal U/S wk 28-30 to R/O fetal goitre
If allergy/neutropenia on PTU: 2nd trimester thyroidectomy
Thyrotoxicosis & Lactation
ATD generally don’t get into breast milk unless at higher doses:
PTU > 450-600 mg/d
MTZ > 20 mg/d
Generally safe
I prefer PTU > MTZ for preg lactating
Take ATD dose just after breast-feeding Should provide 3-4h interval before lactates again
Neonatal Grave’s
Rare, 1% infants born to Graves’ moms
2 types:
Transplacental trnsfr of TSH-R ab (IgG) Present at birth, self-limited
Rx PTU, Lugol’s, propanolol, prednisone
Prevention: TSI in mom 2nd trimester, if 5X normal then Rx mom with PTU (crosses placenta to protect fetus) even if mom is euthyroid (can give mom LT4 which won’t cross placenta)
Child develops own TSH-R ab Strong family hx of Grave’s
Present @ 3-6 mos
20% mortality, persistant brain dysfunction
Postpartum & Thyroid
5% (3-16%) postpartum women (25% T1DM)
Up to 1 year postpartum (most 1-4 months)
Lymphocytic infiltration (Hashimoto’s)
Postpartum Exacerbation of all autoimmune dx
25-50% persistant hypothyroidism
Small, diffuse, nontender goitre
Transiently thyrotoxic Hypothyroid
Postpartum & Thyroid
Distinguish Thyrotoxic phase from Grave’s: No Eye disease, pretibial myxedema
Less severe thyrotoxic, transient (repeat thyroid fn 2-3 mos)
RAI (if not breast-feeding)
Rx: Hyperthyroid symptoms: atenolol 25-50 mg od
Hypothyroid symptoms: LT4 50-100 ug/d to start
• Adjust LT4 dose for symtoms and normalization TSH
• Consider withdrawal at 6-9 months
(25-50% persistent hypothyroid, hi-risk recur future preg)
Postpartum & Thyroid
Postpartum depression When studied, no association between postpartum
depression/thyroiditis
Overlapping symtoms, R/O thyroid before start antidepressents
Screening for Postpartum Thyroiditis HOW: TSH q3mos from 1 mos to 1 year postpartum?
WHO:
– Symptoms of thyroid dysfn.
– Goitre
– T1DM
– Postpartum thyroiditis with prior pregnancy
