Thyroid Disorders in Pregnancy

Management Across the Reproductive Lifecycle

Comprehensive Clinical Guidelines for Hypothyroidism and Hyperthyroidism

Evidence-Based Approach

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Learning Objectives

Understand physiological changes in thyroid function during pregnancy
Recognize classification of thyroid disorders in pregnancy
Master diagnostic criteria and trimester-specific reference ranges
Apply evidence-based management protocols for hypothyroidism
Apply evidence-based management protocols for hyperthyroidism
Understand fetal monitoring and postpartum care considerations
Identify high-risk populations requiring targeted screening

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Introduction & Epidemiology

Global Context

Thyroid disorders affect 10% of Indian adults
Hypothyroidism in pregnancy: 4.8-12% (India)
Hyperthyroidism in pregnancy: 0.05-1.3%
Prevalence of thyroid nodules: 15-21% on ultrasound

Clinical Significance

Maternal thyroid hormone demands increase by ~50%
Critical for fetal neurodevelopment
Untreated OH: 60% risk of fetal loss
Early detection prevents perinatal complications

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Physiological Changes in Pregnancy

Increased TBG: Rising oestrogen elevates thyroxine-binding globulin from early pregnancy, plateauing at 18-20 weeks
hCG Effect: First-trimester hCG (weak TSH-like activity) transiently raises fT4/fT3 and suppresses TSH
Increased Iodine Requirements: Increased thyroid hormone synthesis, raised renal clearance, placental storage, and fetal uptake
Fetal Thyroid Development: Fetal thyroid produces appreciable hormone from 18-22 weeks; maternal T4 supports neurodevelopment throughout
Plasma Volume Expansion: 30-50% increase in third trimester alters hormone distribution

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Classification of Thyroid Function Disorders

Condition	TSH	fT4	Prevalence
Overt Hypothyroidism (OH)	Increased	Decreased	0.2-1%
Subclinical Hypothyroidism (SCH)	Increased	Normal	2.2-10%
Isolated Hypothyroxinaemia (IH)	Normal	Decreased	1.3-8%
Gestational Transient Thyrotoxicosis	Suppressed	Increased	1-5%
Overt Hyperthyroidism (Graves')	Suppressed	Increased	0.05-1.3%
Subclinical Hyperthyroidism	Decreased	Normal	1.5-2%

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Trimester-Specific TSH Reference Ranges

Trimester	Abbott Architect	Beckman Access/DxI	Roche Cobas	Siemens Advia
First	0.09-3.46 mU/L	0.06-3.32 mU/L	0.12-4.10 mU/L	0.06-3.67 mU/L
Second	0.32-3.31 mU/L	0.32-3.31 mU/L	0.11-4.26 mU/L	0.47-4.46 mU/L
Third	0.38-4.34 mU/L	0.34-5.02 mU/L	0.50-4.71 mU/L	0.60-4.60 mU/L

Key Point: Use trimester- and manufacturer-specific pregnancy reference ranges. Non-pregnant reference ranges carry risk of misdiagnosis.

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Iodine Supplementation Guidelines

Recommendations

Target total daily iodine: 200-250 μg in pregnancy and breastfeeding Grade B
Take 150 μg iodine daily as potassium iodide Grade C
Supplementation ideally commenced 3 months pre-pregnancy
Single iodine-containing supplement only

Iodine-Rich Foods

Cow's milk: 50-100 μg/200 mL
Yoghurt: 50-100 μg/150g
Eggs: 20-26 μg each
Cod: 70-190 μg/100g
Haddock: 325-430 μg/100g

Warning: Sustained iodine intake >500 μg daily should be avoided - can cause fetal and maternal thyroid dysfunction.

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Screening Approach: Universal vs Risk-Based

Universal Screening: NOT Recommended

No improvement in overall population outcomes shown Grade C

Risk-Based Targeted Testing

Offer as soon as possible in pregnancy (preferably first trimester)
Test TSH and fT4 simultaneously
High-risk screening misses ~30% of OH/SCH cases

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High-Risk Criteria for Thyroid Screening

Residing in area of moderate-severe iodine insufficiency
Obesity: BMI ≥30 kg/m²
History of prior thyroid dysfunction or surgery
Symptoms of thyroid dysfunction or goitre
First-degree relative with thyroid disease

Autoimmune diseases (T1DM, SLE, RA, Addison's, Coeliac)
Recurrent miscarriages, preterm delivery, IUFD
History of infertility
Use of amiodarone or lithium
Previous head/neck irradiation

Clinical Note: OH in type 1 DM: incidence 16%; in SLE: incidence 11%. Preterm birth rises from 18% (euthyroid SLE) to 65% (SLE + thyroid dysfunction).

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PART I

HYPOTHYROIDISM

Pre-pregnancy, Antenatal & Postpartum Management

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Hypothyroidism: Definitions & Classification

Overt Hypothyroidism

TSH >2.5-3 with low FT4

OR

TSH ≥10 any FT4

0.2-1%

Subclinical

TSH 2.5-10 (T1)

TSH 3-10 (T2/T3)

Normal FT4

2.2-10%

Isolated Hypothyroxinaemia

Normal TSH

Low FT4

Exclude pituitary pathology

1.3-8%

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Hypothyroidism: Pre-pregnancy Optimization

Target TSH: ≤2.5 mU/L in women with overt hypothyroidism and severe SCH (TSH >10 mU/L, normal fT4) Grade B
SCH with TPOAb positivity: Levothyroxine should be considered preconception with titration to TSH ≤2.5 mU/L Grade C
Isolated low fT4: Refer to Endocrinology to exclude secondary hypothyroidism / pituitary pathology Grade C

            Empirical Levothyroxine Dose Increase on Positive Pregnancy Test Grade A
            Self-initiate increase of ~25-30% as soon as pregnancy test positive
Doubling dose on 2 days/week (Monday & Thursday), OR
+25 μg/day for women on ≤100 μg, OR +50 μg/day for women on >100 μg

        

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Hypothyroidism: Newly Diagnosed in Pregnancy

Overt Hypothyroidism / Severe SCH (TSH >10)

Start levothyroxine immediately at 1.6 μg/kg/day
Repeat TFTs in 4 weeks Grade B

Subclinical Hypothyroidism (TSH trimester upper limit - 10)

Levothyroxine should be considered, especially if first trimester or TPOAb positive
Suggested starting dose: 1.0-1.2 μg/kg/day
If not treated: check TFTs every 4-6 weeks up to 20 weeks and at 28 weeks Grade C

Isolated Hypothyroxinaemia

Routine levothyroxine NOT recommended
Recheck TFTs 4-6 weeks after initial testing Grade C

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Subclinical Hypothyroidism: Clinical Associations

Meta-analysis (n=47,045, 19 cohorts):

1.53

Pre-eclampsia OR

1.29

Preterm Birth OR

1.24

SGA OR

1.93

Pregnancy Loss OR

2.16

Placental Abruption OR

2.3

Breech Presentation OR

Benefit of Treatment: Levothyroxine for SCH may reduce pregnancy loss (RR 0.79) and neonatal death (RR 0.35)

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Levothyroxine: Monitoring & Titration

Monitoring Frequency

Every 4-6 weeks until 20 weeks' gestation
Once at 28 weeks' gestation Grade A

Treatment Targets

TSH <2.5 mU/L
fT4 within normal trimester-specific range Grade C

Important Considerations

TSH suppression with free hormones within normal range is NOT associated with adverse effects
Overtreatment risks: Maternal hyperthyroidism associated with ADHD in children; higher natural fT4 associated with lower birthweight, autistic traits, reduced brain cortical volumes
Nausea/vomiting: Administer at times when less likely to vomit; split daily dose; consider IV liothyronine if unable to take orally

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Levothyroxine: Dose Titration

If TSH Above Target - Increase Dose

Trimester	If TSH Above Target	Current Dose (μg)	Increase To (μg)
First	>2.5 mIU/L	25	50
First	>2.5 mIU/L	50	75
First	>2.5 mIU/L	75	100
First	>2.5 mIU/L	100	125
Second/Third	>3 mIU/L	25	50
Second/Third	>3 mIU/L	50	75
Second/Third	>3 mIU/L	75	100
Second/Third	>3 mIU/L	100	125

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Hypothyroidism: Postpartum Management

TSH ≥10 (OH)

Continue levothyroxine at same dose
Repeat TSH 6 weeks postpartum

TSH 2.5/3-10 (SCH)

Discontinue levothyroxine after delivery
Repeat TSH 6 weeks postpartum

                Pre-existing Treatment
                Revert to pre-pregnancy levothyroxine dose 2 weeks postpartum (TBG takes up to 4 weeks to return to pre-pregnancy levels)
Check TSH 6-8 weeks postpartum Grade D

            

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Thyroid Peroxidase Antibodies (TPOAb)

Routine TPOAb Testing: NOT Recommended Grade B

No intervention improves outcomes in euthyroid TPOAb-positive women

Levothyroxine NOT Recommended Grade A

For euthyroid TPOAb-positive women in absence of thyroid dysfunction

TABLET trial (n=952): no improvement in live birth at ≥34 weeks

Known TPOAb Positive but Euthyroid

Offer TFTs at first trimester booking AND at 20 weeks' gestation Grade C

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Consequences of Untreated Hypothyroidism

Maternal Complications

Miscarriage (especially early pregnancy)
Recurrent pregnancy losses
Anaemia
Pre-eclampsia
Gestational diabetes
Abruptio placentae
Postpartum haemorrhage
Increased caesarean section
Rarely: myopathy, congestive heart failure

Fetal/Neonatal Complications

Preterm birth
IUGR
Intrauterine fetal demise
Respiratory distress
Increased perinatal mortality
Cognitive impairment
Neurological impairment
Developmental impairment

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PART II

HYPERTHYROIDISM

Graves' Disease, GTT & Thyroid Storm

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Hyperthyroidism: Overview & Epidemiology

0.05-0.2%

Prevalence in Pregnancy

0.2%

Graves' Disease

1-5%

Gestational Transient Thyrotoxicosis

Common Causes

Graves' Disease: Most common cause - TSH receptor antibodies (TSAb) stimulate thyroid gland
Thyroiditis: Inflammatory conditions
Thyroid Adenoma: Toxic nodules
Multinodular Goitre: Toxic multinodular goitre

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Hyperthyroidism: Pre-pregnancy Counselling

All women of childbearing age with hyperthyroidism should discuss future pregnancy implications
Treatment options: antithyroid drugs (ATDs), radioactive iodine (RAI), or surgery

After Definitive Treatment (RAI/Thyroidectomy)

Wait ≥6 months before conception
Confirm fT4 within reference range on 2 measurements 3 months apart Grade C

TRAb Considerations

If TRAb >3x threshold at 6 months post-treatment: consider further delay Grade D

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Antithyroid Drug Selection in Pregnancy

                First Trimester: PTU Preferred Grade B
                Use PTU in preference to carbimazole (CMZ) while trying to conceive
Lowest effective dose to maintain fT4 in upper half of reference range

            

Switching Protocol

If conceived on CMZ: switch to PTU ASAP and before 10 weeks
CMZ:PTU ratio = 1:20
No benefit of switching after 10 weeks Grade D

After 20 Weeks

Consider switching back to CMZ to avoid PTU hepatotoxicity
Conversion: 200 mg PTU = 10 mg CMZ Grade D

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Graves' Disease: Management in Pregnancy

Discontinuation Strategy: If euthyroid for ≥6 months on low-dose ATD (CMZ <10 mg or PTU <200 mg/day), consider discontinuing with close TFT monitoring Grade D
TFT Monitoring on ATDs: Every 2-4 weeks in first half of pregnancy (TSH + fT4); consider fortnightly when switching drugs, stopping, or adjusting doses; after 20 weeks: 4-8 weekly Grade D
ATD Titration Target: fT4 in upper half of trimester-specific pregnancy reference range - to minimize fetal hypothyroidism risk from transplacental drug passage
Important: Do NOT titrate primarily on TSH (may remain low). No role for fT3/T3.

Block-and-Replace Regimens: NOT Recommended

ATDs cross placenta more efficiently than levothyroxine; high risk of fetal hypothyroidism and goitre

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ATD Teratogenicity: Critical Information

Carbimazole/Methimazole (CMZ/MMI)

Embryopathy risk: 2-4% with exposure at 6-10 weeks
Aplasia cutis, choanal/oesophageal atresia
Abdominal wall defects, urinary/eye abnormalities, VSD
OR for congenital anomalies: 1.88 (95% CI 1.33-2.65)

Propylthiouracil (PTU)

Less severe defects: 2-3% of exposed children
Face/neck cysts, urinary tract abnormalities
OR for congenital anomalies: 1.16-1.41
Risk of hepatotoxicity (irreversible liver damage)

CMZ/MMI and PTU should be considered as two separate teratogens

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Fetal Monitoring in Graves' Disease

TRAb Measurement Grade D

Recommended in first trimester in ALL women with history of Graves' disease (even after definitive treatment)
If above threshold of positivity OR if on ATDs: repeat at 20 and 28 weeks

Fetal Growth Surveillance Grade D

Serial ultrasound biometry + umbilical artery Doppler
Monthly intervals from 26-28 weeks
Indications: Uncontrolled Graves', ATD requirement, or TRAb >3x threshold

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Gestational Transient Thyrotoxicosis (GTT)

Cause: High hCG stimulating TSH receptors; self-limiting; usually resolves by 18-20 weeks
Prevalence: 1-5% of pregnancies
Key Point: Severe nausea and vomiting alone do NOT warrant thyroid testing in absence of specific symptoms/signs of thyrotoxicosis Grade D

Distinguishing GTT from Graves' Disease

Feature	GTT	Graves' Disease
Thyrotoxicosis symptoms BEFORE pregnancy	No	Often
Nausea/vomiting (hyperemesis)	Yes (~60%)	Often absent
Personal/family history	Often absent	Present in ~50%
Goitre	No	Diffuse in 90%
Thyroid eye disease	No	In ~20%
fT3 concentration	Normal in 85%	Increased
TRAb measurement	Normal	Increased

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GTT: Management

                Management: Symptomatic & Supportive Only Grade C
                Anti-emetics, hydration, electrolyte correction
Transient beta-blockers for tachycardia if needed
No antithyroid drugs - no evidence of improved outcomes

            

Diagnostic Confirmation

Serum hCG levels are NOT useful in distinguishing GTT from Graves'
Repeat TFTs 2 weeks later showing declining fT4 without ATDs is supportive of GTT
TSH may remain suppressed longer

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Thyroid Storm & Heart Failure

Thyroid Storm

Life-threatening, hypermetabolic state; rare in pregnancy. Associated with pulmonary hypertension and cardiac failure due to myocardial effects.

Precipitants: Preeclampsia, sepsis, anemia, decompensation

Treatment of Thyroid Storm

Start thionamides
PTU 100 mg loading
Then 200 mg q6h

After 1-2 hours:
Start iodine
Sodium iodide 500-1000 mg IV q8h
OR Lugol solution 10 gtt PO q8h

Heart rate control
Propranolol 10-40 mg PO q4-5h

Corticosteroids for 24h
Dexamethasone 2 mg IV q8h
OR Hydrocortisone 100 mg IV q8h

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Subclinical Hyperthyroidism

Third-generation TSH assays (sensitivity 0.002 mU/mL) enable detection of subclinical thyroid disorders
NOT associated with adverse pregnancy outcomes
Treatment NOT indicated due to potential fetal harm from antithyroid drugs Grade B
Recommend periodic monitoring of symptoms and serum TSH (~50% normalize spontaneously)

Clinical Approach

Routine screening and treatment for subclinical hyperthyroidism in pregnancy are not warranted due to lack of association with adverse outcomes.

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Postpartum Thyroiditis (PPT)

Definition & Epidemiology

Thyroid dysfunction within first 12 months post-delivery in previously euthyroid woman
Autoimmune, associated with anti-TPO and anti-thyroglobulin antibodies
Prevalence: 5-10% of unselected pregnancies
30-50% of TPOAb-positive women develop PPT

Risk Factors

Type 1 DM
SLE
Previous Graves' disease
Hashimoto's thyroiditis
Personal/family history of thyroid disease

Classical Course (Triphasic)

Thyrotoxic phase (2-6 months) → Hypothyroid phase (3-12 months) → Euthyroidism

Only 20-40% have classical form: 20-30% only thyrotoxicosis; 40-50% only hypothyroidism

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PPT: Diagnosis & Management

Routine Testing: NOT Recommended Grade D

Mostly self-limiting condition

When to Test

Women with PPT risk factors and thyrotoxicosis symptoms Grade D
Confirm PPT: serial TFTs every 6 weeks with symptom assessment
If thyrotoxicosis: measure TRAb and consider isotope scan to exclude Graves'

Management

Thyrotoxic phase: ATDs NOT indicated (destructive thyroiditis) Grade B
Beta-blockers if symptomatic (propranolol, metoprolol - safe in breastfeeding) Grade C
Hypothyroid phase: Levothyroxine if very symptomatic or trying to conceive

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Postpartum Care: Hyperthyroidism

TFTs 6-8 weeks post-birth for women with pre-existing hyperthyroidism
Postpartum period carries 3-4× risk of new-onset and relapsed Graves' disease Grade C

Breastfeeding & ATDs Grade C

Both CMZ (up to 20 mg/day) and PTU (up to 450 mg/day) are safe during breastfeeding
Minimal transfer to breast milk: CMZ 0.1-0.2%, PTU 0.007-0.077% of ingested amount
Consider splitting daily dose into 2-3 smaller doses to reduce peak concentrations GPP

Definitive Treatment Postpartum

RAI difficult postpartum due to radiation protection issues; surgery invasive. ATDs are preferred in postpartum hyperthyroidism.

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Thyroid Nodules & Cancer in Pregnancy

Epidemiology

Thyroid nodule prevalence on ultrasound: 15-21%
Clinically apparent nodules: <1%
Thyroid cancer in pregnancy: very rare (14 per 100,000)
More likely diagnosed postpartum than antenatally

Management

New/enlarging nodule: check TFTs and refer to specialist Grade D
FNA can be safely performed at any gestation Grade B
Surgery: ideally 14-22 weeks to minimize miscarriage/preterm labour risk Grade C

Radioactive Agents

Avoided for diagnostic or therapeutic purposes in pregnancy

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Clinical Features: Hypo- vs Hyperthyroidism

Feature	Hypothyroidism	Hyperthyroidism
General	Fatigue, cold intolerance, weight gain	Heat intolerance, weight loss, anxiety
Cardiovascular	Bradycardia, hypertension	Tachycardia, widened pulse pressure
Neurological	Depression, cognitive slowing	Irritability, tremor, insomnia
Dermatological	Dry skin, hair loss, non-pitting edema	Diaphoresis, warm moist skin
Specific Signs	Goitre (Hashimoto's), delayed reflexes	Goitre (Graves'), exophthalmos, thyroid bruit
Obstetric	Infertility, recurrent miscarriage	Preterm labour, fetal tachycardia

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Diagnostic Algorithm: Thyroid Testing

Pregnant Woman
First Antenatal Visit

↓

High-Risk Criteria Present?

↓

YES
Test TSH + fT4

NO
Routine Care

↓

Interpret Using Trimester-Specific
Reference Ranges

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Management Algorithm: Hypothyroidism

TSH >10 or
TSH >2.5-3 + Low FT4
(Overt Hypothyroidism)

↓

Start 50 μg/day
OR 1.6 μg/kg/day

↓

Repeat TSH in 4-6 weeks
Target: TSH <2.5 (T1) or <3 (T2/T3)

TSH 2.5-10 (T1) or 3-10 (T2/T3)
Normal FT4 (Subclinical)

↓

Consider 25 μg/day
Especially if TPOAb+ or 1st trimester

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Management Algorithm: Hyperthyroidism

Confirmed Graves' Disease
Suppressed TSH + High FT4/FT3

↓

First Trimester:
Start PTU

↓

After 20 Weeks:
Switch to CMZ (if needed)

↓

Target: FT4 in Upper Half
of Reference Range

Monitor: TFTs every 2-4 weeks initially, then 4-8 weekly after 20 weeks 588f5625-8fa4-45a2-9e09-6823ad7de8b1