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Thyroid disorders in pregnancy
Dr.K.Saravanan
ECG & ECHO Club of Trichy
Control of thyroid function
Thyroid Disorders & Pregnancy
Specific to Pregnancy :
Transient hyperthyroidism of HG
Postpartum thyroiditis
Neonatal & fetal hyperthyroidism
Neonatal & fetal hypothyroidism
Not specific to Pregnancy :
Thyrotoxicosis , Hypothyroidism
Thyroid nodules , Thyroid neoplasia
Physiological adaptation in pregnancy
Clinical presentation - 1
A 19 year old primi with H/o 54 days
amenorrhea was referred by obstetrician with
C/o palpitations, weight loss of 2-3 months
duration (8 kg), Her haemoglobin was 9.8 g/dl,
HR  120/mt with prominent eye sign.
In a background of clinical suspicion of Graves
disease, the preferred investigation of choice :
1.
2.
3.
4.
TSH, T3, T4
TSH, FT4, FT3
TSH, FT4
TSH, FT4, Anti-TPO antibodies
Thyroid Function Tests in Pregnancyhyperthyroidism
TSH
Low
FT4
Normal
High
FT3
Hyper
thyroidism
Normal
Subclinical
Hyperthyr
oidism
Her TSH was < 0.001 (n 0.3-4.5 mIU/L)and FT4- 8.9 (n 0.932-1.71
ng/dl). Her TPO antibodies were positive. Drug of choice
is Propanolol +
1. Carbimazole
2. Methimazole
3. PTU
•
•
•
•
TSH  low
FT4  high
Clinical  hyperemesis
Observe , fluid therapy
•
•
•
•
•
TSH  low
FT4  high
Clinical  thyrotoxicosis
Anti-TPO antibodies +ve
Treat with PTU
TSH  low
FT4 ,FT3normal
Subclinical hyperthyroidismobserve
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
Hyperthyroidism & Pregnancy
•
•
•
•
•
Useful Physical Signs :
Inappropriately low weight gain for gest. age
Goiter
Lid lag
Muscle weakness
Heart rate >100
Onycholysis
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
Approach in 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 dose by: FT4, TSH
– TSH alone is less useful (lags, hCG suppression)
– Aim for high-normal to slightly elevated hormone levels
– FT4 0.85-1.9 ng/dl and TSH 0.5 – 2.5mIU/L
– 3rd trimester: titrate PTU down & decrease prior to
delivery if TFT’s permit
– Consider fetal U/S wk 28-30 to R/O fetal goitre
• If allergy/neutropenia on PTU: 2nd trimester thyroidectomy
• Propranolol
TO summarize….
•
•
•
•
Arrive at the diagnosis.
Correlate clinically
Rule out hyperemesis
Treat with PTU and propranolol in
hyperthyroidism
• Watch for neutropenia and infections
• Monitor FT4 to assess control
Points to ponder…….
•
•
•
•
Target FT4 is 0.85-1.9 ng/dl
TSH alone not helpful in monitoring PTU dose.
PTU dose adjusted every 3-4 weeks.
Symptoms improve in 3-4 wk but full response
only after 8 weeks.
• Block and replace therapy avoided in
pregnancy due to risk to fetus.
• Fetal monitoring is important
• Subclinical hyperthyroidism-no intervention
.
Clinical Presentation - 2
Known hypothyroidism on 150 mcg Eltroxin with H/o
3 months amenorrhea comes with TSH,T3,T4 results.
TSH-2.5(n 0.3 – 4.5 mIU/L) T4 – 16.4 (n 5.13-14.06 ug/dl) T3 – 3.2 (n
0.84-2.02 ng/dl).
1. Eltroxin should be stopped.
2. Eltroxin dose should be increased in
pregnancy
3. Check FT4 alone
4. Check FT4 ,FT3
Thyroid Function Tests in Pregnancyhypothyroidism
TSH
High
FT4
Normal
Subclinical
Hypothyroidism
Low
Primary
Hypothyroidism
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 hypothyroid mothers vs. normal mothers:
» Average of 7 IQ points less in children
» Increased risk of IQ < 85 (19% vs. 5%)
Causes & Diagnosis of Hypothyroidism
• Causes:
– Hashimoto’s (chronic thyroiditis; most common in developed
countries) & iodine deficiency -> both associated with goiter
– Subacute thyroiditis -> not associated with goiter
– Thyroidectomy, radioactive iodine treatment
– Iodine deficiency (most common worldwide; rare in US)
Symptoms
•
•
•
•
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Fatigue
Constipation
Cold intolerance
Weight gain
Muscle cramps
CTS
Insomnia , lethargy
Points to ponder …..
• Known hypothyroid, eltroxin is increased by
30-50% in first trimester.
• First time diagnosed start eltroxin at 1-2 mcg/kg
/day
• Target TSH is 0.5 – 2.5mU/L
• TSH checked initially at 4-6 weeks and later 8
weeks
• Space eltroxin and vitamin tablets to avoid
interaction.
• Postpartum-dose is reduced
• Recommended iodide salt avg 250 mcg/day
Clinical Presentation - 3
27 year old female and 3 MA with clinical
features suggestive of hypothyroidism has a TSH
 6.8 and FT4  1.2 ng. This is
1.
2.
3.
4.
Overt Hypothyroidism
Subclinical Hypothyroidism
Subacute Thyroiditis
Overt Hyperthyroidism
Recommended approach in this patient
1. Start eltroxin
2. Repeat TSH every 4 weeks until 16-20 weeks
and atleast once between 26-32 weeks
3. Repeat TSH & FT4 every 4 weeks until 16-20
weeks and atleast once between 26-32
weeks
4. No Intervention at all.
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
Takeaways……..
• Thyroid is second commonest endocrine disorder
in pregnancy.
• Untreated hypothyroidism-fetus more affected
• Untreated hyperthyroidism-mother more
affected
• Subclinical hypothyroidism- treat
• Subclinical hyperthyroidism-followup
• Routine screening- not recommended
Management…..
• LT4  1-2 mcg/kg/day
• Dose adjustments by 25-50 mcg
Hyperthyroidism & Pregnancy
• TPO antibodies are increased in (80–90%) of
patients with Graves disease
+ Other autoimmune disorders
• (TRAbs) are increased in >80% of patients
with Graves disease
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
EFFECTS OF PREGNANCY ON THYROID
PHYSIOLOGY
Physiologic Change
Thyroid-Related Consequences
↑ Serum thyroxine-binding globulin
↑ Total T4 and T3; ↑ T4 production
↑ Plasma volume
↑ T4 and T3 pool size; ↑ T4
production; ↑ cardiac output
D3 expression in placenta and (?) uterus
↑ T4 production
First trimester ↑ in hCG
↑ Free T4; ↓ basal thyrotropin; ↑ T4
production
↑ Renal I- clearance
↑ Iodine requirements
↑ T4 production; fetal T4 synthesis during
second and third trimesters
↑ Oxygen consumption by fetoplacental
unit, gravid uterus, and mother
↑ Basal metabolic rate; ↑ cardiac
output
Thyroid function in mother and foetus
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
• 6. Women with type I diabetes.
• 7. Women with other autoimmune disorders.
• 8. Women with infertility who should have screening
with TSH as part of their infertility work-up.
• 9. Women with previous therapeutic head or neck
irradiation.
• 10. Women with a history of miscarriage or preterm
delivery.
Why treat hypothyroidism in preg?
•
•
•
•
To prevent:
Premature birth
LBW
Abruption,PPH
Impaired neuropsychological development in
child
Physiologic thyroid adaptations in
pregnancy
•
•
•
•
•
TBG
FT4, FT3
hCG
TSH
Plasma iodide
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?
Hyperthyroidism & Pregnancy
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Complications
First-trimester spontaneous abortions.
High rates of still births and neonatal deaths.
low birth weight infants : ↑ 2-3 folds.
Premature delivery.
Fetal or neonatal hyperthyroidism.
Intrauterine growth retardation .
Case Presentation - 2
• A 19 year old primi with H/o 54 days
amenorrhea was referred by obstetrician for
C/o palpitations, weight loss of 2-3 months
duration (8 kg), Her hemaglobin was 9.8 g/dl,
HR  120/mt with prominent eye sign.
In a background of clinical suspicion of Graves
disease, the preferred investigation of choice :
1.
2.
3.
4.
TSH, T3, T4
TSH, FT4, FT3
TSH, FT4
TSH, Anti-TPO antibodies
Her TSH was < 0.001 and FT4 8.9. Her TPO
antibodies were positive. Drug of choice:
1.
2.
3.
4.
Carbimazole
Methimazole
Betablockers
PTU
Known hypothyroidism on 150 kg LT4 lost following and came 2
years later with H/o 3 months amenorrhea. She had stopped LT4
since conception and has checked TSH now which was 2.8
1.
2.
3.
4.
Restart LT4 in preconception dose
Wait for 4 weeks and recheck TSH
Restart LT4 in low dose
Wait till delivery and then restart LT4
The Fetal Thyroid
• Begins concentrating iodine at 10-12 weeks
• Controlled by pituitary TSH by approximately
20 weeks
10-12 wks of gestation:
Fetal thyroid concentrates iodine, synthesize T3
and T4. The fetal pituitary differentiates.
Prior to 12 weeks the mother is the sole
source of thyroid hormone to the fetus. Fetal
thyroid function is at low basal level till 18-20
wks At birth TSH 70uU/ml. Day 2max. TSH
12uU/ml
• Treatment indicated if FT4>2.0ng/dl
• PTU 50-100mg q12 hours in pt. with minimal symptoms
(doses>200 mg of PTU can result in fetal goiter & Hypothyroidism
• Pt with large goiters & long disease duration may require larger
initial doses 100-150mg tid
• Clinical improvement (weight gain & ↓in HR) is noted in the first
2-6 wks, with FT4 improvement in the first 2 wks
• Once clinical improvement occurs the dose of PTU is ↓by half.
Goal to keep FT4 at the upper limit of normal, with least amt of
medication
• In 30% of pt PTU may be D/C’ed in the last 4 - 8wks of pregnancy
(Mestman. Best Practice & Research clin endoMetb.,200,vol
18,no. 2,27-88)
• CENTRAL CONGENITAL HYPOTHYROIDISM
• Uncontrolled maternal hyperthyroidism
• High levels of serum T4 in maternal circulation cross
placental barrier
• Feed back to the fetal pituitary with suppression of
fetal pituitary TSH
• Diagnosis : Neonatal serum FT4 is low & serum TSH is
low normal or inappropriate for the level of FT4. In
majority of infants there is a return to euthyroidism in
a few weeks to months.
• Rx with LT4 and long term follow up
Physiologic Changes in Thyroid Function
During Pregnancy
Maternal Status
TSH
Free T4
Free
Thyroxine
Index (FTI)
Total T4
Total T3
Resin
Triiodothyronine
Uptake
(RT3U)
No change
No change
No change
Increase
Increase
Decrease
Hyperthyroidism
Decrease
Increase
Increase
Increase
Increase or
no change
Increase
Hypothyroidism
Increase
Decrease
Decrease
Decrease
Decrease or
no change
Decrease
**initial
screening
test**
Pregnancy
Physiologic adaptation during pregnancy
• increase in thyroid-binding globulin
– secondary to an estrogenic stimulation of TBG synthesis
and reduced hepatic clearance of TBG ;two to threefold
– levels of bound proteins, total thyroxine, and total
triiodothyronine are increased and resin triiodothyronine
uptake (RT3U) is decreased
– begins early in the first trimester, plateaus during
midgestation, and persists until shortly after delivery
– decrease in its hepatic clearance,estrogen-induced
sialylation
• free T4 and T3 increase slightly during the first trimester in
response to elevated hCG. decline to nadir in third trimester
• human chorionic gonadotropin (hCG)
– intrinsic thyrotropic activity
– begins shortly after conception, peaks around gestational
week 10,declines to a nadir by about week 20
– directly activate the TSH receptor
– partial inhibition of the pituitary gland (by cross-reactivity
of the α subunit)
• transient decrease in TSH between Weeks 8 and 14
• mirrors the peak in hCG concentrations
– 20% of normal women, TSH levels decrease to less than
the lower limit of normal
• Graves' hyperthyroidism occurs in
approximately 0.2 percent of women, and it
occurs in approximately one to five percent of
infants born to these mothers [2-4].
Hyperthyroidism & Pregnancy
Causes
•
•
•
•
•
•
•
Graves disease (85–90% of all cases)
Sub-acute thyroiditis
Toxic MNG
Toxic adenoma
TSH-dependent thyrotoxicosis
Iodine-induced hyperthyroidism
Exogenous T3 or T4
Management
•
•
•
•
•
•
•
TSH >2.5  monitor
Target TSH  0.5—2.5
Always check FT4
TPO antibodies if TSH is 3-10
TSH to be checked every 8 weeks
LT4  1-2 mcg/kg/day
Dose adjustments by 25-50 mcg
Neonatal Grave’s
• Rare, 1 - 5% 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, persistent brain dysfunction
Screen for fetal goiter even in mothers treated
previously with RAI or ATD before
consumption.
Pregnancy: screen for thyroid dysfn ?
• Universal screening not currently recommended:
• ACOG, AACE, Endo Society, ATA
• Controversial !
• Definitely screen:
• Goitre, Family H/o 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
• 8. SCREENING FOR THYROID DYSFUNCTION DURING
PREGNANCY
• 1. Women with a history of hyperthyroid or
hypothyroid disease, PPT, or thyroid lobectomy.
• 2. Women with a family history of thyroid disease.
• 3. Women with a goiter.
• 4. Women with thyroid antibodies (when known).
• 5. Women with symptoms or clinical signs suggestive
of thyroid underfunction or overfunction, including
anemia,elevated cholesterol, and hyponatremia.
Hyperthyroidism & Pregnancy
• TPO antibodies are increased in (80–90%) of
patients with Graves disease
+ Other autoimmune disorders
• (TRAbs) are increased in >80% of patients
with Graves disease