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Pregnancy & Endocrinology

William HarperHamilton General Hospital

McMaster University

www.drharper.ca

Objectives

Thyroid Disorders & Pregnancy

Normal thyroid phsyiology & pregnancy

Hypothyroidism & pregnancy Thyrotoxicosis & pregnancy

Postpartum thyroid dysfunction

Diabetes & Pregnancy Gestational DM

Type 1 & Type 2 DM & Pregnancy

Case 1

31 year old female

Somalia Canada 3 years ago

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

Case 1

1. How would you characterize her

hypothyroidism?

2. What are the ramifications of pregnancy to

thyroid function/dysfunction?

LowHigh

FT4 FT4 & FT3

1° Hypothyroid

Central

Hypothyroid

TRH Stim.

equivocal

MRI, etc.

1° Thyrotoxicosis

2° thyrotoxicosis

•Endo consult

•FT3, rT3

•MRI, α-SU

Case 1

GH, IGF-1 normal

LH, FSH, E2, progesterone, PRL normal for

pregnancy

8 AM cortisol 345, short ACTH test normal

MRI: normal pituitary

TGAB, TPOAB negative

Normal pregnancy, delivery, baby, lactation

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

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, esophagealatresia, 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

• 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!

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

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,

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 earliestprenatal 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: 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

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

Diagnosis difficult: hCG effect:

• Suppressed TSH (9%) +/- FT4 (14%) until 12 wks

• Enhanced if hyperemesis gravidarum: 50-60% withabnormal 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 wksFT4, FT3, T4, T3

Thyroid Ab’s

Examine

NormalizesStill 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

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’spermit to minimize risk of fetal goitre

Consider fetal U/S wk 28-30 to R/O fetal goitre

If allergy/neutropenia on PTU: 2nd trimesterthyroidectomy

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 Rxmom with PTU (crosses placenta to protect fetus) even if momis 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

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 depression When studied, no association between postpartum

depression/thyroiditis

Overlapping symtoms, R/O thyroid before start antidepressents

Screening for Postpartum ThyroiditisHOW: TSH q3mos from 1 mos to 1 year postpartum?

– Symptoms of thyroid dysfn.

– Goitre

– T1DM

– Postpartum thyroiditis with prior pregnancy

Objectives

Thyroid Disorders & Pregnancy

Normal thyroid phsyiology & pregnancy

Hypothyroidism & pregnancy Thyrotoxicosis & pregnancy

Postpartum thyroid dysfunction

Diabetes & Pregnancy

Gestational DM

Type 1 & Type 2 DM & Pregnancy

Gestational Diabetes Mellitus (GDM)

“Glucose intolerance with onset/discoveryduring pregnancy”

Some T2DM picked up during pregnancy Rarely some T1DM may present during pregnancy

Prevalence higher than previously thoughtin Canada:

3.5 - 3.8% non-Aboriginal (but multi-ethnic)population

8.0 - 18.0% Aboriginal

Gestational Diabetes Mellitus (GDM)

Prior “selective screening” resulted in missed

cases: Caucassians < 25 y.o.

No personal or FHx of DM

No prior infant with birth weight > 4 kg

Treatment of GDM reduces perinatal morbidity

Diagnosis GDM maternal anxiety ? Evidence controversial for this

Therefore all women should be screened

* Presence of multiple risk factors warrants earlier

screening (preconception, 1st & 2nd trimester)

GDM: Morbidity

Maternal Fetal/NeonatalMacrosomia

(birth trauma,cesarian)

Macrosomia

(shoulder dystocia)

Preeclampsia RDS

Polyhydramnios Neonatal hypoglycemia

Perinatal mortality (fetus) Neonatal hypocalcemia

Postpartum IFG, IGT, DM3-6 mos: 16-20 %

Lifetime: 30-50 %

Neonatal jaundice

Obesity later in life?

IGT, IFG, or DM later in life?

GDM Treatment

CBG qid: FBS, 1-2h pc Dietary: 3 small meals, 3 small snacks

If glycemic targets not met: Insulin

Multiple Daily Injection (MDI) best

Insulins: regular, lispro, aspart ? (still new)

No glargine (stimulates IGF-I receptors)

GDM Treatment

No OHA’s, not standard of care yet.

Glyburide

Minimal crossing of placenta, 3rd

trimester most organogenesiscomplete

1 RCT: 404 women, mild GDM, glyburide vs. insulin, no

difference in outcomes

Further study before safety established

Metformin Retrospective cohort:

• preeclampsia & stillbirth

• Bias: DM women older, more obese

GDM: Labour & Postpartum

NPO during Labour: Monitor CBG q1h, target BS 4 – 6.5 mM

Hypoglycemia (BS < 4 mM): IV D5W

Hyperglycemia (BS > 6.5 mM): IV D5W & IV insulin gtt

Postpartum: D/C all insulin (IV and SC)

CBG in recovery:

• > 10 mM CBG qid, may need Rx for T2DM

• < 10 mM stop CBG monitoring

FBS or 2hPG in 75g OGTT within 6 mos postpartum and prior to anyfuture planned pregnancies

Encourage: breast feeding, healthy diet, exercise to prevent futureType 2 DM, GDM

Screen for future T2DM (GDM is a risk factor)

T1DM, T2DM & Pregnancy Congenital anomalies: 2-3x increased risk

Cardiac malformations

Neural Tube Defects 1 % risk

Folate 1-4 mg/d (Prenatal vitamin 0.4-1.0 mg)

d/c ACE-I and ARBs methyldopa, etc.

Dilated eye exam: preconception & 1st trimester

T2DM: d/c OHA insulin

Good glycemic control prior to conception: Prevent unplanned pregnancies: OCP or 2x barrier

Initiate MDI and qid (FBS, 2hPC) prior to preg

CSII also another option

T1DM, T2DM & Pregnancy

< 8.0 ?

T1DM & T2DM: Labour & Postpartum

NPO during Labor: Monitor CBG q1h, target BS 4.0 – 6.5 mM

IV D5W & IV insulin gtt (Hamilton Health Sciences Protocol)

Postpartum: D/C all IV insulin

Insulin resistance/requirements rapidly fall during & after labor

T2DM: monitor CBG qid

• Restart insulin if CBG > 10 mM

T1DM: postpartum honeymoon

• CBG q1h x 4h, then q2h x 4h, then q4h

• Restart MDI insulin S.C. when CBG > 10 mM

No OHA, ACE-I or ARB during breast feeding!

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