# DNB EXAM NOTES: Management of Thyroid Disorders in Pregnancy
**Source: RCOG Green-top Guideline No. 76 (2025)**

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## PHYSIOLOGICAL CHANGES IN THYROID FUNCTION DURING PREGNANCY ⭐

- Maternal thyroid hormone demands increase by **~50%** during pregnancy
- **Increased oestrogen** raises thyroxine-binding globulin (TBG) from early pregnancy, plateauing at 18-20 weeks
- To compensate, **T4 and T3 production increases** in first half of pregnancy; steady state reached by mid-gestation
- **First trimester hCG** (has weak TSH-like activity) transiently raises fT4/fT3 and suppresses TSH
- As hCG declines from mid-gestation: fT4 and fT3 fall gradually, TSH rises slightly
- **Iodine requirement increases** due to: increased thyroid hormone synthesis + increased renal iodine clearance + placental storage + fetal thyroid uptake from 10-12 weeks
- Fetal thyroid begins producing hormones at **18-22 weeks**; completely dependent on maternal T4 before this
- Fetus continues to receive maternal T4 until birth

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## DEFINITIONS AND PREVALENCE ⭐

| 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%–2.0% |

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## THYROID FUNCTION TESTS IN PREGNANCY ⭐

### Key Points:
- **Trimester- and manufacturer-specific pregnancy reference ranges** must be used for TSH and fT4 [Grade B]
- If specific ranges unavailable, **TSH upper limit of 4.0 mU/L** in first trimester is pragmatic [Grade C]
- Treatment target: **TSH < 2.5 mU/L** with fT4 in trimester-specific normal range [Grade C]
- For women on thyroid medication: use manufacturer-specific pregnancy reference ranges

### Iodine Requirements:
- Recommended daily intake: **200-250 mcg** when planning pregnancy, during pregnancy and breastfeeding
- Supplementation: **150 mcg/day iodine** (as potassium iodide, present in common prenatal supplements) [Grade C]
- **>500 mcg/day** can cause serious adverse effects (to be avoided)
- Iodine deficiency is the leading global cause of **preventable neurodevelopmental defects**

### Who to Test:
- **Universal screening is NOT recommended** for low-risk populations
- Test **high-risk subpopulations** as soon as possible (preferably first trimester) [Grade D]

**Risk factors for thyroid dysfunction:**
- Prior thyroid disease or surgery
- Family history of autoimmune thyroid disease
- TPOAb positive
- Type 1 diabetes or other autoimmune disease
- Previous thyroid irradiation
- Goitre
- Symptoms of thyroid disease
- Infertility or recurrent miscarriage
- Severe obesity (BMI > 40)
- Age >30 years
- Residing in iodine-deficient areas

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## HYPOTHYROIDISM IN PREGNANCY ⭐⭐

### Adverse Effects of Untreated/Inadequately Treated OH:
- Spontaneous miscarriage
- Perinatal death
- Pre-eclampsia
- Pregnancy-induced hypertension
- Preterm birth
- Low birth weight
- Postpartum haemorrhage
- Impaired fetal neurodevelopment (correlated with degree of TSH elevation)

### Additional risks from SCH:
- Pregnancy loss (OR 1.93)
- Hypertensive disorders (OR 1.54)
- Placental abruption (OR 2.16)
- Breech presentation (OR 2.3)
- Neurodevelopmental defects

### PRECONCEPTION Management:
- **Overt hypothyroidism / Severe SCH (TSH >10 mU/L):** Titrate levothyroxine to achieve TSH ≤ **2.5 mU/L** preconception [Grade B]
- **SCH (TSH between ULN and 10 mU/L):** Consider levothyroxine especially if TPOAb positive [Grade C]

### DURING PREGNANCY Management:

**Treatment thresholds:**
- **SCH with TSH 10-15 mU/L** (some labs upper limit 10 mU/L): Start levothyroxine
- **SCH with TSH between pregnancy ULN and 10 mU/L:** Consider levothyroxine (especially if TPOAb positive or newly diagnosed in 1st trimester) [Grade C]
- **Isolated hypothyroxinaemia:** Levothyroxine NOT recommended routinely

**Dose increase on positive pregnancy test:** ⭐
- Women already on levothyroxine should **self-initiate empirical dose increase** immediately on positive pregnancy test
- Method: **Double the dose on 2 days per week** (i.e., approximately 29% increase) [Grade A]

**Monitoring during pregnancy:**
- Check **TSH + fT4 every 4-6 weeks until 20 weeks**, then once at 28 weeks [Grade A]
- After dose change: repeat TFTs in 4-6 weeks
- Target: TSH < 2.5 mU/L + fT4 within trimester-specific normal range

**Treatment:**
- Oral **levothyroxine (T4) ONLY** - do NOT use desiccated thyroid or combined T4/T3 preparations in pregnancy (insufficient fetal brain transfer)
- Up to **40% of women on levothyroxine** may require further dose adjustments during pregnancy

### POSTPARTUM:
- Return to **pre-pregnancy levothyroxine dose 2 weeks postpartum**
- Confirm with TFTs at **6 weeks postpartum**

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## HYPERTHYROIDISM IN PREGNANCY ⭐⭐

### Gestational Transient Thyrotoxicosis (GTT):
- Common: **1-5%** of pregnancies in Europe
- Caused by hCG-mediated TSH suppression (especially in hyperemesis gravidarum)
- Usually **benign and self-limiting**
- **NO antithyroid drugs required** - management is supportive only [Grade C]
- Treatment: anti-emetics, IV fluids, electrolyte correction, beta-blockers (if symptomatic tachycardia)
- Distinguish from Graves' disease using: clinical features + TRAb measurement + fT3

### Differentiating Gestational Transient Thyrotoxicosis vs Graves' Disease:
| Feature | GTT | Graves' Disease |
|---|---|---|
| Onset | Early (before 20 weeks) | Any time |
| TRAb | Negative | Positive |
| Goitre | Absent | Often present |
| Ophthalmopathy | Absent | May be present |
| History of autoimmune disease | No | May be present |
| Hyperemesis | Often | Uncommon |

### True Hyperthyroidism (Graves' / Toxic Nodular):
- **Untreated overt hyperthyroidism** is associated with: pre-eclampsia, preterm birth, fetal growth restriction, maternal heart failure

**Antithyroid Drugs (ATDs) - Choice:** ⭐
- **Preconception / Early pregnancy (before 10 weeks):** Use **PTU** (propylthiouracil) in preference to carbimazole [Grade B/D]
- **After 20 weeks:** Switch to **carbimazole (CMZ)** to avoid PTU hepatotoxicity [Evidence Level 3]
- Conversion: **20 mg CMZ = 15 mg MMI = 200 mg PTU** (conversion ratio 20:1 PTU:CMZ)
- Dose: **lowest effective dose** targeting fT4 in **upper half of pregnancy reference range**
- Titration NOT based primarily on TSH (may remain suppressed)

**Why PTU preferred in early pregnancy?** ⭐
- CMZ/MMI-associated **embryopathy** at 6-10 weeks gestation: aplasia cutis, choanal/oesophageal atresia, abdominal wall defects, urinary/eye abnormalities, ventricular septal defects
- CMZ/MMI increases odds of congenital anomalies by **OR 1.88** (CI 1.33-2.65)
- PTU still teratogenic but less so than CMZ in early pregnancy

**Adverse effects of ATDs (both):**
- Minor: skin rash (3-5%)
- Serious: agranulocytosis (0.15%)
- Liver failure: 0.1% - almost exclusively PTU

**Monitoring on ATDs:**
- First half of pregnancy: TFTs every **2-4 weeks** [Grade D]
- After 20 weeks: TFTs every **4-8 weeks** [Grade D]

**Special situations with Graves':**
- Already euthyroid for 6 months on low-dose ATD: **consider discontinuing** ATD with close monitoring [Grade D]
- Graves' commonly **improves with advancing gestation** due to immunosuppression
- After stopping ATDs: if fT4 normal on 2 consecutive occasions 2-4 weeks apart, reduce monitoring to 4-8 week intervals

### Fetal Monitoring in Hyperthyroidism:
- Elevated maternal TRAb (>3x ULN) increases risk of **fetal/neonatal hyperthyroidism**
- TRAb crosses the placenta and can stimulate fetal thyroid
- Fetal monitoring by USS (fetal growth, heart rate, goitre) if TRAb elevated

### Postpartum Hyperthyroidism:
- ATDs preferred over radioactive iodine or surgery (practical difficulties with young children)
- Risk of **new onset Graves'** increases 3-4 fold postpartum
- Risk of **relapsed Graves'** increases postpartum

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## THYROID ANTIBODIES (TPOAb) ⭐

- Prevalence: 5-31% across populations; ~10% in women with miscarriage/subfertility
- **Routine TPOAb testing NOT recommended** in euthyroid women [Grade B] - no intervention improves outcomes
- **Levothyroxine NOT recommended** for TPOAb-positive euthyroid women [Grade A - 1++ evidence]

### If already known TPOAb-positive but euthyroid:
- Offer TFTs in **first trimester** (at first antenatal contact) and at **20 weeks** [Grade C]
- Reason: increased risk of progression to hypothyroidism especially in first half of pregnancy

### TPOAb associations (even in euthyroid state):
- Increased miscarriage risk
- Preterm birth
- Postpartum thyroiditis (PPT)
- Pre-eclampsia (when combined with thyroid dysfunction)
- Gestational diabetes (when combined with thyroid dysfunction)

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## THYROID NODULES AND GOITRE IN PREGNANCY ⭐

- Incidence of clinically apparent nodules/goitre in pregnancy is **low** in iodine-replete areas
- Ultrasound-detected nodules more common with increasing parity and age
- When new nodule/goitre diagnosed: assess for local symptoms (tracheal compression), exclude malignancy and hyperthyroidism
- **Fine needle aspiration (FNA):** Safe at any gestation if malignancy suspected [Grade B]
- **Thyroid surgery:** If required, ideally perform between **14-22 weeks of gestation** [Grade C] to reduce risk of miscarriage and preterm labour
- Women with enlarged thyroid: manage possible airway obstruction (anaesthetic team alert)

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## POSTPARTUM THYROIDITIS (PPT) ⭐

- Occurs in **5-10%** of women in first year postpartum
- Autoimmune, associated with TPOAb positivity
- **Triphasic pattern** (classic):
  1. **Thyrotoxic phase:** 1-4 months postpartum (destructive, not true hyperthyroidism - ATDs not helpful)
  2. **Hypothyroid phase:** 4-8 months postpartum
  3. **Recovery/euthyroid phase:** by 12 months (most recover)
- ~50% with PPT develop **permanent hypothyroidism**

### Management of PPT:
- **Thyrotoxic phase:** Beta-blockers if symptomatic; ATDs usually NOT indicated (not true hyperthyroidism)
- **Hypothyroid phase:** Levothyroxine if symptomatic or if trying to conceive; taper after 12 months if not planning pregnancy
- **Expectant management** with 6-weekly TFT monitoring until euthyroidism restored [Grade D]
- Monitor TSH **annually** in all women with PPT history (risk of permanent hypothyroidism) [Grade C]
- If planning next pregnancy: test TFTs preconception and as soon as possible in pregnancy

### Prevention of PPT:
- Levothyroxine prophylaxis: NOT recommended [Grade B]
- Iodine supplementation: NOT recommended for prevention
- Selenium supplementation: ONE small trial showed potential benefit; evidence inconclusive

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## BREASTFEEDING AND ANTITHYROID DRUGS ⭐

- Both PTU and CMZ are compatible with breastfeeding
- PTU preferred in breastfeeding by some guidelines (less transfer to breast milk)
- Consider splitting total daily dose of CMZ or PTU into **2-3 smaller doses** to reduce peak concentrations and breast milk transfer [GPP]
- Infant thyroid function monitoring may be considered

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## IODINE IN PREGNANCY - SUMMARY ⭐

| Parameter | Value |
|---|---|
| Recommended daily intake | 200-250 mcg |
| Supplementation dose | 150 mcg/day (as potassium iodide) |
| Timing | From preconception (ideally) |
| Upper safe limit | <500 mcg/day |
| Fetal thyroid iodine uptake starts | 10-12 weeks |
| Fetal thyroid hormone production | 18-22 weeks |

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## MULTIDISCIPLINARY CARE ⭐

- Women with thyroid disorders should be seen in **joint MDT clinics** (obstetric + endocrine/thyroid)
- Clear designated primary clinician for continuity
- Care provided by clinicians with appropriate experience

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## KEY NUMBERS TO REMEMBER FOR DNB ⭐⭐

| Fact | Number |
|---|---|
| TSH target preconception (hypothyroid) | ≤ 2.5 mU/L |
| TSH target in pregnancy | < 2.5 mU/L |
| TSH upper limit (pragmatic) if no local range | 4.0 mU/L (first trimester) |
| Iodine daily requirement in pregnancy | 200-250 mcg |
| Iodine supplementation dose | 150 mcg/day |
| Maternal thyroid demand increase | ~50% |
| TFT monitoring on levothyroxine | 4-6 weekly until 20 weeks, then at 28 weeks |
| TFT monitoring on ATDs (1st half) | Every 2-4 weeks |
| TFT monitoring on ATDs (post 20 weeks) | Every 4-8 weeks |
| Levothyroxine dose increase on +ve test | Double dose 2 days/week (~29% increase) |
| Return to pre-pregnancy dose postpartum | 2 weeks after delivery |
| TFT check postpartum (hypothyroid) | 6 weeks postpartum |
| PTU to CMZ conversion ratio | 200 mg PTU = 10 mg CMZ (20:1) |
| Thyroid surgery timing if needed | 14-22 weeks gestation |
| PPT incidence | ~5-10% |
| PPT permanent hypothyroidism risk | ~50% |
| CMZ teratogenic window | 6-10 weeks gestation |
| CMZ/MMI congenital anomaly OR | 1.88 (CI 1.33-2.65) |
| ATD minor adverse effects | 3-5% (skin rash) |
| ATD agranulocytosis | 0.15% |
| ATD liver failure (PTU) | 0.1% |

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## QUICK CLINICAL DECISION FRAMEWORK (DNB EXAM) ⭐⭐

```
HYPOTHYROIDISM IN PREGNANCY:
Overt hypothyroidism → Levothyroxine (T4 only) + target TSH <2.5 mU/L
Severe SCH (TSH >10) → Start Levothyroxine
Mild-Mod SCH (TSH > preg ULN, <10) → Consider Levothyroxine (esp. if TPOAb+)
Isolated Hypothyroxinaemia → No treatment routinely
Already on Levothyroxine → Double dose 2 days/week immediately on +ve test

HYPERTHYROIDISM IN PREGNANCY:
GTT (hCG-mediated) → Supportive only (NO ATDs)
Graves' / True Hyperthyroid → ATDs: PTU before 10 wks; switch to CMZ after 20 wks
Target fT4 → Upper half of pregnancy reference range (NOT TSH)

POSTCONCEPTION SWITCH RULE:
Conceived on CMZ → Switch to PTU ASAP, before 10 weeks gestation
```

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*Source: RCOG Green-top Guideline No. 76 - Management of Thyroid Disorders in Pregnancy (2025), BJOG 132:e130-e161*