Longitudinal evaluation of recurrent thyrotoxicosis in a single patient across four pregnancies: a case report and literature review.

Summary: We report the case of a 37-year-old woman who presented with hyperemesis gravidarum at 11 weeks of gestation. Laboratory examination revealed severe thyrotoxicosis (TSH: <0.005 μIU/mL, FT3: 12.95 pg/mL, FT4: 3.93 ng/dL) with negative anti-TSH receptor antibody, while serum human chorionic gonadotropin (hCG) was markedly elevated at 198,983 mIU/mL. She was diagnosed with gestational transient thyrotoxicosis (GTT), although the presence of thyroid-stimulating antibody raised suspicion for concomitant Graves' disease (GD). Because of severe and clinically burdensome thyrotoxic symptoms, including excessive sweating and weight loss, propylthiouracil therapy was initiated, but thyrotoxicosis recurred after 20 weeks of gestation alongside elevated serum hCG levels, prompting a switch to thiamazole. Genetic testing revealed no TSHR mutations. Postpartum, both hCG and thyroid hormone levels normalized without treatment. During the second pregnancy, she experienced a miscarriage at nine weeks. During the third pregnancy, an elective abortion was performed due to a fetal genetic disorder. Both pregnancies were marked by severe thyrotoxicosis, consistent with GTT. During the fourth pregnancy, at 11 weeks, she developed hyperemesis gravidarum and was diagnosed with GTT. The persistently elevated thyroglobulin levels (>200 ng/mL; reference range:, <33.7 ng/mL) were also compatible with a possible contribution from painless thyroiditis (PT). Serum hCG levels normalized after the second trimester. Recurrent and sustained thyrotoxicosis during pregnancy across multiple pregnancies in the same patient is rare and requires careful differentiation among possible etiologies, including GTT, GD, and PT. This case underscores the importance of comprehensive monitoring of placental function, thyroid autoimmunity, and thyroiditis throughout pregnancy to ensure accurate diagnosis and tailored management for both mother and fetus. Learning points: The diagnosis of recurrent thyrotoxicosis in pregnancy is complex, as distinct entities can overlap clinically. Comprehensive phenotyping - incorporating thyroid autoantibodies, serum hCG, Tg, and ultrasound - guides diagnosis; reserve TSHR testing for atypical or persistent cases. Careful longitudinal monitoring across pregnancies enables optimized maternal-fetal outcomes.