Managing Graves' Disease in Women of Childbearing Potential

Abstract and Introduction

Abstract

The management of Graves' disease (GD) in women of childbearing potential has multiple specific complexities. Many factors are involved, which differ at the various stages from preconception, conception, first trimester, later pregnancy, postpartum and lactation, with both maternal and foetal considerations. The incidence and significance of the risks incurred from antithyroid drugs (ATDs) in pregnancy have been re-evaluated recently and must be balanced against the risks of uncontrolled hyperthyroidism during childbearing years. Contraception is advised until hyperthyroidism is controlled. ATD cessation should be considered in those who are well controlled on low dose therapy before conception and in early pregnancy. Advice on iodine supplementation does not generally differ in those with GD. Radioiodine (RAI) is contraindicated from 6 months preconception until completion of breastfeeding. In all women who have a history of GD, monitoring of TSH receptor antibodies (TRAb) is strongly recommended during pregnancy, and if elevated, foetal monitoring and assessment of thyroid function in the neonate are required. Of note, RAI increases TRAb for up to a year, making this treatment option even less attractive in this patient group. A small amount of ATD is transferred into breast milk but low doses are safe during lactation. Routine periodic thyroid function testing is recommended in remission to detect postpartum GD recurrence. We present our approach to the Clinical Question 'How to manage GD in women of childbearing potential?'

Introduction

Graves' disease (GD) is common in women during childbearing years, affecting 0.4%–1.3% before pregnancy, and 0.2% during pregnancy.^[1] Occurrence or relapse of Graves' hyperthyroidism is more likely in the first trimester and postpartum.^[2]

Pregnancy-related GD complications are associated with poorly controlled hyperthyroidism, and include miscarriage, pre-eclampsia, premature labour, thyroid storm, stillbirth and maternal congestive cardiac failure.^[3] Foetal and neonatal hyperthyroidism, which result from transplacental passage of maternal stimulatory TSH-receptor antibodies (TRAb), also causes increased morbidity and mortality.^[4,5] Foetal central hypothyroidism can develop from maternal hyperthyroidism impairing maturation of the foetal hypothalamic-pituitary-thyroid axis.

Table 1. Management options for Graves' disease in women of child-bearing potential
	Benefits	Risks	Considerations in pregnancy
Antithyroid drugs	• Effective treatment, often achieving euthyroid state within 3 months of treatment • Easily titrated or discontinued • Relatively inexpensive	• Adverse effects (mild 5%–8%; severe 0.2%) • Birth defects associated with use in early pregnancy (2%–4%) • Hepatotoxicity (PTU) • Recurrence upon discontinuation in 50%–70%	• Precaution with MMI in first trimester of pregnancy (switch to PTU) • Lowest effective dose should be used • Minimal transfer in breast milk
Radioactive iodine	• Definitive therapy of hyperthyroidism • Oral administration • Reduces goitre • Minimal adverse effects	• Repeat therapy may be required • Lifelong need for levothyroxine following ablation • Post-dose TRAb elevation increases foetal hyperthyroidism risk • Worsening of thyroid eye disease	• Contraindicated in pregnancy and breast-feeding • Avoid within 6 months of conception • Euthyroid women may have persistently elevated TRAb
Thyroidectomy	• Definitive therapy of hyperthyroidism • Euthyroid state easy to achieve with levothyroxine • Remission of autoimmunity may gradually occur • No goitre	• Lifelong need for levothyroxine • Surgical complications (2%–5%) • Neck scar	• Can be undertaken in the second trimester if GD is refractory to medical therapy or ATD not tolerated