• Credits

  • Section Writer: Dr. Om J Lakhani
  • Section Editor: Dr. Om J Lakhani

• Video lecture

• Q. What are the potential complications of hyperthyroidism in pregnancy?

  • Abortion
  • Low birth weight
  • Premature labor
  • Stillbirth
  • Pre-eclampsia
  • Heart failure

• Q. Which are the two most common causes of hyperthyroidism in pregnancy?

  • Graves’ disease
  • HCG mediated hyperthyroidism
    • Gestational transient thyrotoxicosis
    • Hyperemesis gravidarum
    • Trophoblastic hyperthyroidism
    • Familial gestational hyperthyroidism

• Q. What test is done to differentiate the above two diagnoses?

  • TSH receptor antibody using 3rd generation TBII assay

• Q. Using T3, T4, how will you distinguish the two?

  • Graves disease has more T3 elevation
  • HCG mediated have both T3 and T4 elevation but more of T4

• Q. At what time does HCG peak, and by what time does it fall?

  • Peaks at 10-12 weeks
  • Falls by 14-18 weeks

• Q. Which patients with hyperthyroidism in pregnancy are treated?

  • Patients having overt moderate to severe hyperthyroidism due to Graves’ disease, gestational trophoblastic disease, and  other causes are treated
  • Patients with mild hyperthyroidism with T3/T4 < 1.5 times the ULN of the non-pregnant range are not treated

• Q. Which is the only form of HCG-mediated hyperthyroidism that is treated?

  • One secondary to gestational trophoblastic disease with overt hyperthyroidism and moderate to severe symptoms

• Q. What is the goal of the treatment of hyperthyroidism in pregnancy (what are the TFT targets) ?

  • T4 in upper limit or just above the trimester-specific normal range
  • If a trimester-specific range is not available, keep free T4 in the upper limit of the normal range of non-pregnant women using the lowest possible dose
  • TSH- lower limit or normal or suppressed

• Q. What is the role of beta-blockers in the management of hyperthyroidism in pregnancy?

  • IT IS GENERALLY AVOIDED
  • Beta-blockers in low doses may be given in the initial part of the management of hyperthyroidism in pregnancy, mainly for symptomatic control (In special circumstances ONLY)
  • They should be weaned off once ATD effects have taken over
  • Typically, atenolol in a dose of 25-50 mg or Propranolol 20 mg TID may be given in the initial phase
  • Generally not given for more than 2-6 weeks

• Q. What are the potential adverse effect of beta-blocker on the fetus ?

  • Bradycardia
  • Hypoglycemia
  • Low birth weight
  • Respiratory depression

• Q. Which of the two – PTU or Methimazole (MMI)/Carbimazole crosses the placenta?

  • Both cross the placenta
  • However, teratogenicity is more observed with Methimazole/Carbimazole and not PTU

• Q. Which is the most common teratogenicity with MMI?

  • Aplasia cutis

• Q. Which are other potential manifestations?

  • Choanal atresia
  • Tracheoesophageal fistula
  • Patent vitellointestinal duct
  • Omphalocele
  • Omphalomesntric duct

• Q. What is the difference in potential liver toxicity of PTU vs. MMI ?

  • PTU- produces hepatocellular inflammation- hepatitis while MMI produces cholestasis

• Q. Which ATD are used when during pregnancy ?

  • If women already on treatment with MMI becomes pregnant – switch to PTU as soon as pregnancy is confirmed
  • In second trimester switch to MMI or Carbimazole again
  • PTU 300 mg = 10-15 mg of MMI

• Q. Should LFT be monitored while on PTU therapy  ?

  • No
  • Because the hepatotoxicity is idiosyncratic and hence no point of LFT monitoring
  • If however monitoring is done, PTU is stopped if Liver enzymes are >3 times ULN
  • Stop PTU and monitor LFT, if it is rising – refer to hepatologist

• Q. What is done in the third trimester ?

  • Autoimmune thyroid disease often improves in 3rd trimester
  • If a patient goes into remission in 3rd trimester than ATD can be potentially tapered and stopped if TFT is normal and TRAb is negative
  • Some women switch from TSH stimulating to blocking antibody
  • Stopping of drug is possible in 1/3rd of women

• Q. What is the starting dose of PTU / MMI in pregnancy ?

  • Start with lowest possible dose
    • PTU- 50 mg TID
    • MMI- 5-10 mg
    • CBZ- 5-15 mg

• Q. What are the consequence of under-treatment and over treatment of hyperthyroidism in pregnancy on the fetal thyroid function ?

  • Undertreatment – may lead to central hypothyroidism due to negative feedback of excess T4/T3
  • Overtreatment- fetal primary hypothyroidism

• Q. Graves disease improves postpartum, True or false ?

  • False
  • It may worsen postpartum
  • Also women in remission – may relapse in postpartum period

• Q. Which are 2 important consequences of uncontrolled hyperthyroidism in 3rd trimester?

  • Neonatal thyrotoxicosis
  • Low birth weight

• Q. What is the indication for surgery in hyperthyroidism in pregnancy ?

  • When a patient has allergy or agranulocytosis due to ATD
  • In such cases, surgery can be completed in 2nd trimester
  • However, risk of surgical complications are higher

• Q. What preparation is done before surgery ?

  • Beta-blockers and
  • Low dose of SSKI- 1-3 drops/day for 7-10 days before surgery

• **Nursing mothers **

• Q. Which is secreted more in breast milk- PTU or MMI ?

  • MMI is excreted more in breast milk as it is less protein-bound unlike PTU
  • However, since dose of MMI is much lower- risk of fetal complications are less
  • There are very rare/ no cases of fetal complications due to drug presence in breast milk – for either drug
  • Hence MMI is preferred in nursing mothers because of less risk of hepatotoxicity

• Q. Should TFT of infant be monitored if mother is on MMI ?

  • Generally no
  • However, if MMI dose is >20 mg – then monitor TFT of infant every 1-3 months

• **Fetal hyperthyroidism **

• Q. What TRAb level in 2nd and 3rd trimester predict the occurrence of neonatal hyperthyroidism ?

  • 2nd/ 3rd trimester TRAb levels > 3 times ULN or > 5 IU/l predict the occurrence of neonatal hyperthyroidism with 100% sensitivity and 40% specificity.

• Q. When is the TRAb level typically determined during pregnancy ?

  • TRAb level is tested typically at 18-22 weeks of pregnancy

• Q. What is the risk of fetal hyperthyroidism in women with Graves disease in pregnancy ?

  • 1-5% risk

• Q. What are the signs of fetal hyperthyroidism ?

  • Fetal HR >160 bpm
  • Fetal goiter – with central blood flow on Doppler
  • Craniosynostosis
  • Advanced bone age
  • Poor growth
  • Rare cases- heart failure and hydrops

• Q. When is TRAb monitoring done in 3rd trimester and what is its role ?

  • It is done at 24-28 weeks
  • TRAb levels >3-5 times the ULN suggest a high risk of fatal complication

• Q. A woman has past history of Graves disease but currently in remission. Should TRAb be measured in such women?

  • Yes
  • TRAb must be measured at 20-24 weeks and if >3-5 times ULN fetal monitoring is required
  • Women may be in remission but TRAb may persist and hence monitoring is necessary

• Q. What are the types of assays for TRAb  ?

  • TBII assay- just tells about presence of antibodies but does not tell about function – it is less expensive and generally adequate test in pregnancy
  • TSI assay – tells about function of the TRAb- stimulatory or not but more expensive

• Q. How is the monitoring of the fetus done in case of TRAb antibodies being positive ?

  • Fetal heart rate monitoring and regular ultrasound

• Q. What is THE characteristic of goiter in fetal hyperthyroidism ?

  • They have central flow  on color doppler which is not seen in fetal goiter due to hypothyroidism

• Q.. Can fetal thyroid function be measured  ?

  • Yes
  • But umbilical vein sampling at 20 weeks
  • However, this is not routinely recommended

• Q. When is fetal thyroid function done ?

  • It is done if there is fetal goiter and it is not sure whether the fetus has hypothyroidism or hyperthyroidism due to maternal ATD treatment

• Q. If the mother is euthyroid, but fetal hyperthyroidism is confirmed- what is done ?

  • Mother is treated with ATD despite being euthyroid

• Q. How can you differentiate fetal hypothyroidism from fetal hyperthyroidism ?

  • Fetal hypothyroidism vs Fetal hyperthyroidism
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