hyperthyroidism in pregnancy

physiology

• hCG Effect: hCG shares an $\alpha$-subunit with TSH $\to$ stimulates TSH receptors in T1.
• Net Result: Transient $\uparrow$ fT4 and reciprocal $\downarrow$ TSH (nadir at 10-12 weeks).
• Reference Ranges: Trimester-specific ranges must be used. TSH <0.1 mIU/L is seen in ~5% of normal pregnancies in T1.

diagnosis & aetiology

The major clinical decision is distinguishing Gestational Transient Thyrotoxicosis (GTT) from Graves’ Disease.

Feature	Gestational Transient Thyrotoxicosis (GTT)	Graves’ Disease
Pathophysiology	hCG stimulation of TSH-R	TRAb (TSH-R Antibody) stimulation
Association	Hyperemesis gravidarum, multiple gestation, molar pregnancy	Personal/Family Hx of Autoimmune disease
Physical Exam	Dehydration, weight loss (from vomiting)	Goitre, Orbitopathy, Pretibial myxoedema
TRAb Titres	Negative	Positive (95% sensitivity)
Course	Self-limiting (resolves by 14–18 weeks)	Chronic / Persistence
Treatment	Supportive (fluids/anti-emetics)	Thionamides (PTU/MMI)

red flag

Radioactive Iodine (RAI) scanning is CONTRAINDICATED in pregnancy. Diagnosis relies on clinical features and antibody testing (TRAb).

management: graves’ disease

Goal: Maintain maternal fT4 at the upper limit of normal (ULN) or slightly above, using the lowest effective dose.

• Rationale: Fetal thyroid is more sensitive to antithyroid drugs (ATDs) than maternal thyroid. Aggressive normalisation of maternal TSH risks fetal goitre and hypothyroidism.

pharmacological approach (the switch)

The choice of thionamide is driven by trimester-specific toxicity profiles.

• Pre-conception: Attempt to achieve euthyroidism. If on low dose MMI (≤5-10mg), consider trialing cessation early in pregnancy if remission suspected.
• Trimester 1 (T1): Propylthiouracil (PTU)
  • Reason: Methimazole (MMI) is associated with embryopathy (aplasia cutis, choanal atresia, tracheoesophageal fistula) during organogenesis (weeks 6–10).
• Trimester 2 & 3: Switch to Methimazole (MMI)
  • Reason: PTU carries a black-box warning for hepatotoxicity (fulminant hepatic necrosis).
  • Timing: Switch usually occurs after 16 weeks.
  • Dose Conversion: 10 mg MMI $\approx$ 150–200 mg PTU.

block and replace

NEVER use “Block and Replace” (High dose ATD + Levothyroxine) in pregnancy. ATDs cross the placenta (causing fetal hypo) but Levothyroxine does not cross sufficiently to rescue the fetus.

surgical management

• Indications: Severe allergy to both ATDs, non-adherence, or massive goitre causing compression.
• Timing: Optimal in Trimester 2 (safest for fetus/uterus).
• Prep: Beta-blockers + Potassium Iodide (KI) for 10 days pre-op (safe for short course).

fetal surveillance

Maternal IgG antibodies (TRAb) cross the placenta after 20 weeks, risking fetal thyrotoxicosis.

who to monitor?

1. Current Graves’ disease.
2. History of Graves’ treated with RAI or Surgery (mother is euthyroid/hypo, but antibodies persist).
3. Previous infant with neonatal Graves’.

protocol

1. Check TRAb at first visit.
2. If TRAb elevated ($>3\times$ ULN) or mother on ATDs:
   • Repeat TRAb at 18–22 weeks.
   • Repeat TRAb at 30–34 weeks (predicts neonatal risk).
3. Fetal Ultrasound: Monitor for signs of fetal thyrotoxicosis:
   • Heart rate >160 bpm.
   • Fetal Goitre.
   • IUGR / Hydrops.
   • Advanced bone age.

postpartum & breastfeeding

• Relapse Risk: High risk of Graves’ relapse or “immune rebound” post-delivery.
• Breastfeeding: Safe with ATDs.
  • Preferred: Methimazole (lower transfer into milk, better hepatotoxicity profile).
  • Max Doses: MMI 20mg/day or PTU 450mg/day considered safe.
  • Timing: Take medication after breastfeeding to minimize peak transfer.

clinical pearl: neonatal graves

Neonatal Graves’ is typically transient (1-3 months) as maternal antibodies clear. However, if the mother was on high-dose ATDs, the neonate may present with hypothyroidism at birth (drug effect), followed by hyperthyroidism days later (drug clears, antibodies persist).

thyroid storm in pregnancy

• Precipitants: Labour (induction/C-section), infection, pre-eclampsia.
• Management: Same as non-pregnant (Beta-blockers, PTU, Iodide, Steroids, Cooling) but requires aggressive fetal monitoring.
• Contraindication: Do not use radioactive iodine.