thyroid disorders in pregnancy

Thyroid disorders in pregnancy

Dr.K.SaravananECG & ECHO Club of Trichy

Control of thyroid function

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

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. TSH, T3, T4

2. TSH, FT4, FT3

3. TSH, FT4

4. TSH, FT4, Anti-TPO antibodies

Thyroid Function Tests in Pregnancy-Thyroid Function Tests in Pregnancy-hyperthyroidismhyperthyroidism

TSH

FT4

High

SubclinicalHyperthyr

oidism

Hyperthyroidism

Normal

FT3

Low

Normal

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

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

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 & PregnancyHyperthyroidism & Pregnancy

Useful Physical Signs :•Inappropriately low weight gain for gest. age Goiter •Lid lag •Muscle weakness

•Heart rate >100 •Onycholysis


• 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 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

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.

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

Thyroid Function Tests in Pregnancy-Thyroid Function Tests in Pregnancy-hypothyroidismhypothyroidism

TSH

FT4

Low

Primary Hypothyroidism

Normal

Subclinical Hypothyroidism

High

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

• 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

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

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.

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


• 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

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

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


• 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?


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. TSH, T3, T4

2. TSH, FT4, FT3

3. TSH, FT4

4. TSH, Anti-TPO antibodies

Her TSH was < 0.001 and FT4 8.9. Her TPO antibodies were positive. Drug of choice:

1. Carbimazole2. Methimazole3. Betablockers4. 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. Restart LT4 in preconception dose2. Wait for 4 weeks and recheck TSH3. Restart LT4 in low dose4. 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

**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

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].

http://www.uptodate.com/contents/evaluation-and-management-of-neonatal-graves-disease/abstract/2-4


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.


• 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

thyroid disorders in pregnancy

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