Transcript Pregnancy & Endocrinology William Harper Hamilton General Hospital McMaster University www.drharper.ca Objectives  Thyroid Disorders & Pregnancy      Normal thyroid phsyiology & pregnancy Hypothyroidism & pregnancy Thyrotoxicosis & pregnancy Postpartum thyroid.

Pregnancy & Endocrinology
William Harper
Hamilton 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.
2.
How would you characterize her
hypothyroidism?
What are the ramifications of pregnancy to
thyroid function/dysfunction?
TSH
Low
High
FT4 & FT3
FT4
Low
Low
High
1° Hypothyroid
2° thyrotoxicosis
Central
1° Thyrotoxicosis
Hypothyroid
If
equivocal
TRH Stim.
•Endo consult
•FT3, rT3
•MRI, α-SU
High
MRI, etc.
RAIU
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:



ATD (PTU & MTZ):


MTZ > PTU
TSH-R Ab (stim or block)
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
• 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!
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:



Definitely screen:


Goitre, FHx thyroid dysfn., prior postpartum thyroiditis,
T1DM
Ideally, check TSH preconception:



ACOG, AACE, Endo Society, ATA
Controversial!
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:





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
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 – 0.4
TSH < 0.1
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
 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
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/discovery
during pregnancy”



Some T2DM picked up during pregnancy
Rarely some T1DM may present during pregnancy
Prevalence higher than previously thought
in 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/Neonatal
Macrosomia
(birth trauma,cesarian)
Macrosomia
(shoulder dystocia)
Preeclampsia
RDS
Polyhydramnios
Neonatal hypoglycemia
Perinatal mortality (fetus)
Neonatal hypocalcemia
Postpartum IFG, IGT, DM
3-6 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 organogenesis
complete
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 any
future planned pregnancies
Encourage: breast feeding, healthy diet, exercise to prevent future
Type 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!
END