Graves

Management of Neonates Born to Mothers With Graves’ Disease

  • Authors and Affiliations:

    • Daniëlle C.M. van der Kaay, MD, PhD, et al. from the Division of Endocrinology, The Hospital for Sick Children, University of Toronto.

    • Emphasizes the collaborative effort in planning, drafting, and reviewing the manuscript among the authors.

Overview

  • Risk to Newborns: Newborns of mothers with Graves’ disease (GD) are at increased risk for developing neonatal hyperthyroidism, which can lead to significant morbidity and mortality.

  • Current Guidelines: Lack of consensus guidelines for managing these cases necessitated a literature review to establish a management approach.

Background

  • Prevalence:

    • Maternal hyperthyroidism prevalence: 0.1% - 2.7%.

    • Transient GD in infants ranges from 1.5% - 2.5%, potentially up to 20% in observational studies.

  • Causative Mechanisms:

    • TSH receptor antibodies (TRAb) are responsible for GD and freely cross the placenta during the latter half of pregnancy.

    • Two types of TRAb: TSH-stimulating antibodies induce excess thyroid hormone production, while blocking antibodies do not initiate signaling.

Management Algorithm

  1. Initial Risk Assessment:

    • Base assessment on maternal TRAb levels:

      • Negative → no follow-up needed.

      • Positive or unavailable → newborn considered "at risk" for hyperthyroidism.

  2. Cord Blood Testing:

    • Determine TRAb levels as soon as possible to guide discharge decisions.

  3. Thyroid Function Tests:

    • Not necessary to measure cord TSH and fT4 levels.

  4. Follow-Up Testing:

    • Perform fT4 and TSH levels at days 3-5 and then again at days 10-14, with clinical follow-up until 2-3 months.

  5. Treatment Protocol:

    • Methimazole (MMI) as first line; adjunctive β-blockers for sympathetic hyperactivity when necessary.

    • Potassium iodide may be used in refractory cases.

  6. Monitoring Frequency:

    • Weekly assessment of MMI-treated infants until stable.

  7. Understanding Potential Hypothyroidism:

    • Be aware of the risks of central or primary hypothyroidism in affected newborns.

Clinical Significance of Maternal TRAb

  • Maternal TRAb levels may persist post-treatment, affecting the newborn.

  • High maternal TRAb correlates with increased hyperthyroidism risk in newborns.

  • Evaluating TRAb levels at 20-24 weeks gestation is recommended.

Neonatal Signs and Symptoms of GD

  • Symptoms include:

    • Goiter, low birth weight, irritability, diarrhea, and cardiac issues, among others.

  • Diagnosis can be complicated due to overlaps with other conditions such as sepsis.

  • Severe cases have been associated with high mortality rates.

Treatment Considerations

  • Treatment initiation may prevent complications such as heart failure or developmental issues.

  • Guidelines suggest MMI treatment based on objective measures of hyperthyroidism.

  • There is no clear consensus on treating asymptomatic newborns with hyperthyroidism.

  • Ongoing monitoring of thyroid function is critical in this population.

Timing and Frequency of Assessments

  • Initial TFTs should be performed between days 3-5 of life. If normal, follow-ups may be ceased after 2 weeks.

  • For at-risk infants, continued monitoring up to 3 months is advisable.

Conclusion

  • Effective management of neonatal hyperthyroidism due to maternal GD is crucial for preventing morbidity and mortality.

  • Ongoing refinement of management algorithms based on research findings will enhance care for these patients.

Key Terms

  • ATD: Antithyroid drug.

  • TB: Thyroid Binding.

  • TFT: Thyroid function test.

  • TRAb: TSH receptor antibodies.

  • GD: Graves’ disease.

  • MMI: Methimazole.

  • PTU: Propylthiouracil.