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Pregnancy & Hormonal
Disorders
• Thyroid Disorders & Pregnancy
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Normal thyroid phsyiology & pregnancy
Hypothyroidism & pregnancy
Thyrotoxicosis & pregnancy
Postpartum thyroid dysfunction
• Diabetes & Pregnancy
• Gestational DM
• Type 1 & Type 2 DM & Pregnancy
TSH
High
Low
FT4
FT4 & FT3
High
Low
Low
Central
Hypothyroid
1° Hypothyroid
2° thyrotoxicosis
If
equivocal
TRH Stim.
•Endo consult
•FT3, rT3
•MRI, α-SU
MRI, etc.
High
1° Thyrotoxicosis
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
• 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
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
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
* Regardless of cause of hypothyroidism (Hashimoto’s, thyroidectomy) initial
LT4 dose increase is usually required early (~ week 8), before 1st prenatal
visit!
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?
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
TSH > 20
Increase dose by 50-75 ug/d
Increase dose by 100 ug/d
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
• Causes:
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Graves’ disease
TMNG, toxic adenoma
Thyroiditis
Hydatiform mole
Gestational hCG-asscociated Thyrotoxicosis
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Hyperemesis gravidarum   hCG
60%  TSH, 50%  FT4
Resolves by 20 wks gestation
Only Rx with ATD if persists > 20 wk
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
Still suppressed
Normalizes
Hyperemesis Gravidarum
• 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
Don’t treat with PTU
Abnormal TFT’s past 20 wk
Treat Hyperthyroidism (PTU)
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
• 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:
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Symptoms of thyroid dysfn.
Goitre
T1DM
Postpartum thyroiditis with prior pregnancy