TSH, TRAb positivity associated with rebound Graves’ hyperthyroidism in early pregnancy
For pregnant women with well-controlled Graves’ hyperthyroidism, subnormal thyroid-stimulating hormone levels and thyrotropin-receptor antibody positivity at drug withdrawal were linked to a rebound of Graves’ hyperthyroidism.
The findings were published in the journal Thyroid.
According to study background, use of antithyroid drugs carries potential risk for teratogenic effects.
“For women with well-controlled hyperthyroidism on a low dose of antithyroid drugs, drug withdrawal upon pregnancy is recommended by international medical guidelines,” Xin Hou, PhD, of the NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases in Shenyang, Liaoning, China, and colleagues wrote. “Therefore, it is necessary to determine the characteristics of patients suitable for antithyroid drug withdrawal, subsequent changes in thyroid function following antithyroid drug discontinuation, and its impact on pregnancy and offspring outcomes.”
The researchers conducted a prospective study involving 63 pregnant women with well-controlled Graves’ hyperthyroidism who had stopped antithyroid drugs during early pregnancy. Researchers followed patients until the end of pregnancy and culled data on pregnancy outcomes.
Data indicated that 31.7% of patients experienced a hyperthyroidism rebound. Compared with patients with either normal TSH levels or negative thyrotropin-receptor antibody (TRAb), those with subnormal TSH levels (< 0.35 mIU/L; OR = 5.12; 95% CI, 1.29-20.34; P = .03) or positive TRAb (> 1.75 IU/L; OR = 3.79; 95% CI, 1.17-12.3; P = .02) at the time of antithyroid drugs withdrawal had a higher risk for rebound.
Additionally, rebound was more likely for patients with both subnormal TSH and TRAb positivity at the time of antithyroid drug withdrawal than those with normal TSH and negative TRAb (83.3% vs. 13%; OR = 33.33; 95% CI, 2.83-392.6; P = .003).
In other data, the prevalence of adverse pregnancy outcomes increased among patients experiencing rebound compared with those who did not (55% vs. 9.3%; OR = 11.92; 95% CI, 3.08-46.18; P = .0002).
“Subnormal TSH levels and TRAb positivity at the time of antithyroid drug withdrawal in early pregnancy may be associated with rebound of Graves’ hyperthyroidism,” Hou and colleagues concluded. “Rebound of hyperthyroidism during pregnancy may increase the risk of adverse pregnancy outcomes. Larger prospective studies are needed to confirm these findings.”
The researchers added, “Clinicians should discuss the pros and cons of antithyroid drug withdrawal early in pregnancy, especially with pregnant women with subnormal TSH and/or positive TRAb.”
Perspective
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Given the potential teratogenic effects of antithyroid drugs, especially in the first 6 to 10 weeks of gestation, the American Thyroid Association and European Thyroid Association both recommend consideration of stopping these drugs in patients who are pregnant who would be considered low risk for recurrence based on factors established in nonpregnant patients (low TRAb; less than 6 months of treatment with antithyroid drugs; prepregnancy TSH values within reference range; and low daily dose of antithyroid drugs). However, studies are limited regarding these recommendations in pregnancy.
In their study, Hou and colleagues evaluated outcomes of a cohort of 63 women who met criteria to stop antithyroid drugs in early pregnancy, before 6 weeks’ gestation. The results showed more than two-thirds of patients did not have recurrence of Graves’ hyperthyroidism during pregnancy, and approximately one-third of patients had recurrence, 50% of these occurring in gestational weeks 6 to 10. The prevalence of adverse pregnancy outcomes was significantly higher in patients who had recurrence (55% vs. 9.3%; OR = 11.92; 95% CI, 3.08-46.18; P = .0002) despite restarting of antithyroid drugs.
These results support the recommendation to stop antithyroid drugs in the appropriate patient as most patients will remain euthyroid in pregnancy, while emphasizing the importance of careful selection of patients given the adverse pregnancy outcomes associated with recurrence. The study results showed that patients with subnormal TSH and positive TRAb at baseline were much more likely to experience a recurrence compared with those with normal TSH and negative TRAb (83.3% vs. 13%; OR = 33.33; 95% CI, 2.93-392.6; P = .003).
In this study, recurrence occurred very early in pregnancy, supporting recommendations for close monitoring of thyroid function tests once antithyroid drugs are stopped (every 1 to 2 weeks). No cases of recurrence were reported after 20 weeks, corresponding with maternal immune adaptations in pregnancy and supporting recommendations that the interval of testing may be extended in the latter half of pregnancy.
The results of this study are important to clinical practice and support current practice guidelines.
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