thyroid disorders in pregnancy dr.k.saravanan ecg & echo club of trichy
TRANSCRIPT
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Thyroid disorders in pregnancy
Dr.K.SaravananECG & ECHO Club of Trichy
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Control of thyroid function
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Thyroid Disorders & PregnancyThyroid Disorders & PregnancySpecific to Pregnancy : Transient hyperthyroidism of HG Postpartum thyroiditis Neonatal & fetal hyperthyroidism Neonatal & fetal hypothyroidismNot specific to Pregnancy : Thyrotoxicosis , Hypothyroidism Thyroid nodules , Thyroid neoplasia
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Physiological adaptation in pregnancy
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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.
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In a background of clinical suspicion of Graves disease, the preferred investigation of choice :
1. TSH, T3, T4
2. TSH, FT4, FT3
3. TSH, FT4
4. TSH, FT4, Anti-TPO antibodies
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Thyroid Function Tests in Pregnancy-Thyroid Function Tests in Pregnancy-hyperthyroidismhyperthyroidism
TSH
FT4
High
SubclinicalHyperthyr
oidism
Hyperthyroidism
Normal
FT3
Low
Normal
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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. Carbimazole2. Methimazole3. PTU
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TSH lowFT4 ,FT3normal
Subclinical hyperthyroidismobserve
• TSH low• FT4 high• Clinical hyperemesis• Observe , fluid therapy
• TSH low• FT4 high• Clinical thyrotoxicosis• Anti-TPO antibodies +ve• Treat with PTU
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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
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Hyperthyroidism & PregnancyHyperthyroidism & Pregnancy
Useful Physical Signs :•Inappropriately low weight gain for gest. age Goiter •Lid lag •Muscle weakness
•Heart rate >100 •Onycholysis
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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
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Approach in Pregnant & Suppressed TSH
TSH < 0.1 TSH 0.1 – 0.4
Recheck in 5 wksFT4, FT3, T4, T3Thyroid Ab’sExamine
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
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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
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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
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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.
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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
pregnancy3. Check FT4 alone
4. Check FT4 ,FT3
Clinical Presentation - 2
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Thyroid Function Tests in Pregnancy-Thyroid Function Tests in Pregnancy-hypothyroidismhypothyroidism
TSH
FT4
Low
Primary Hypothyroidism
Normal
Subclinical Hypothyroidism
High
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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%)
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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)
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Symptoms
• Fatigue• Constipation• Cold intolerance• Weight gain• Muscle cramps• CTS• Insomnia , lethargy
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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
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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. Overt Hypothyroidism2. Subclinical Hypothyroidism3. Subacute Thyroiditis4. Overt Hyperthyroidism
Clinical Presentation - 3
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Recommended approach in this patient
1. Start eltroxin 2. Repeat TSH every 4 weeks until 16-20 weeks
and atleast once between 26-32 weeks3. Repeat TSH & FT4 every 4 weeks until 16-20
weeks and atleast once between 26-32 weeks
4. No Intervention at all.
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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
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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
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Management…..
• LT4 1-2 mcg/kg/day• Dose adjustments by 25-50 mcg
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Hyperthyroidism & PregnancyHyperthyroidism & 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
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TSH
LowHigh
FT4 FT4 & FT3
Low
1° Hypothyroid
Low
Central Hypothyroid
TRH Stim.
Ifequivocal
MRI, etc.
High
1° Thyrotoxicosis
High
2° thyrotoxicosis
•Endo consult•FT3, rT3•MRI, α-SU
RAIU
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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
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Thyroid function in mother and foetus
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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
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• 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.
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Why treat hypothyroidism in preg?
To prevent:•Premature birth•LBW•Abruption,PPH•Impaired neuropsychological development in child
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Physiologic thyroid adaptations in pregnancy
• TBG• FT4, FT3• hCG• TSH• Plasma iodide
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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?
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Hyperthyroidism & PregnancyHyperthyroidism & Pregnancy
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 .
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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.
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In a background of clinical suspicion of Graves disease, the preferred investigation of choice :
1. TSH, T3, T4
2. TSH, FT4, FT3
3. TSH, FT4
4. TSH, Anti-TPO antibodies
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Her TSH was < 0.001 and FT4 8.9. Her TPO antibodies were positive. Drug of choice:
1. Carbimazole2. Methimazole3. Betablockers4. PTU
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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. Restart LT4 in preconception dose2. Wait for 4 weeks and recheck TSH3. Restart LT4 in low dose4. Wait till delivery and then restart LT4
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The Fetal Thyroid
• Begins concentrating iodine at 10-12 weeks • Controlled by pituitary TSH by approximately
20 weeks
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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
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• 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)
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• 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
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Physiologic Changes in Thyroid Function During Pregnancy
Maternal Status TSH
**initial screening
test**
Free T4 Free Thyroxine Index (FTI)
Total T4 Total T3 Resin Triiodo-
thyronine Uptake (RT3U)
Pregnancy 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
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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
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• 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
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• 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].
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Hyperthyroidism & PregnancyHyperthyroidism & 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
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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
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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.
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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
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• 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.
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Hyperthyroidism & PregnancyHyperthyroidism & 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