To investigate the clinical characteristics, diagnosis and treatment strategies of pregnant women with thyroid hormone resistance syndrome (SRTH).

One pregnant woman with SRTH (patient 1) who visited the Department of Internal Medicine of Longgang District Maternity & Child Healthcare Hospital of Shenzhen City in November 2023 was selected. A retrospective analysis was conducted to collect the clinical data of pregnant woman 1, and to summarize and analyze her clinical manifestations, diagnosis and treatment process. Chinese and English keywords including " resistance to thyroid hormone" " pregnant woman" and " resistance to thyroid hormone in pregnancy" were used to retrieve relevant literature about pregnancy complicated with SRTH from CNKI, Wanfang Data Knowledge Service Platform, PubMed and Web of Science (WoS). The retrieval period covered September 1, 2004 to July 1, 2026. The retrieved literature was systematically analyzed to summarize the clinical characteristics and key diagnosis-treatment points of pregnant women with SRTH. The protocol of this study complied with the requirements of the Helsinki Declaration of the World Medical Association revised in 2013.

①Patient 1 was a 29-year-old primipara with last menstrual period on September 17, 2023. She presented to the internal medicine outpatient department of our hospital on November 22, 2023 with a chief complaint of abnormal thyroid function for more than 10 years. Her thyroid dysfunction was first detected on physical examination more than 10 years ago, without obvious clinical manifestations, and she did not receive standardized management at that time. Six years prior to presentation, she developed goiter and prominent hypermetabolic symptoms accompanied by elevated serum free thyroxine (FT4), and was misdiagnosed with hyperthyroidism at an outside hospital. After radioactive iodine-131 therapy, her hypermetabolic symptoms resolved completely, without subsequent generalized edema or cold intolerance. During pre-pregnancy preparation in May 2021, a physical examination at another hospital revealed elevated levels of serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and FT4, while plain and contrast-enhanced pituitary MRI showed no remarkable abnormalities. Starting from March 2023, the outside hospital initiated levothyroxine (LT4) replacement therapy at a dose of 50 μg/d under the tentative diagnosis of hypothyroidism post radioactive iodine-131 ablation, with regular thyroid function monitoring. Her serum TSH remained persistently elevated despite treatment. The LT4 dosage was gradually titrated up to 175 μg/d in November 2023; dose escalation only induced a mild reduction in serum TSH while further raising serum FT4. Therefore, LT4 was discontinued in December 2023, and serum FT4 levels returned to normal after discontinuation of the drug. In March 2024, the gene test results of pregnant woman 1 showed that there was a c. 1036C>T(p.Leu346Phe) mutation (NM_001128177.1) in the thyroid hormone receptor β (THRβ) gene (chr3: 24169098), and she was diagnosed as SRTH patient. In June 2024, she delivered a male neonate vaginally at 39 weeks of gestation. Neonatal thyroid function test results were unremarkable, with only mild elevation of thyroid autoantibodies. Genetic screening of the newborn showed no pathogenic variants in the THRβ gene. The infant was followed up to 1 year of age, presenting with normal physical growth and consistently normal thyroid function. ② Literature review: Three relevant studies involving 17 pregnant women with SRTH (patients 2 to 18) were retrieved per the predefined search strategy. Together with patient 1, a total of 18 pregnant women with SRTH were included for comprehensive analysis. These 18 pregnant women had a total of 23 singleton pregnancies. Thyroid function characteristics during pregnancy: 1 case (patient 1) had synchronously elevated serum FT4 and TSH levels; 1 case (patient 2) had typical hyperthyroidism; 1 case (patient 3) had normal thyroid function; 1 case (patient 5) had mildly elevated serum FT4 in early pregnancy; and the remaining 14 patients had normal serum TSH levels and elevated serum FT4 levels. SRTH management during pregnancy: Two cases (patients 10 and 12) used LT4 to improve hypothyroidism symptoms during pregnancy; three cases (patients 2, 15, and 18) used propylthiouracil to treat hyperthyroidism; two cases (the first pregnancy of patient 7 and patient 17) used methimazole to suppress high FT4 levels; three cases (patients 6, 8, and 9) did not report SRTH management during pregnancy; and the remaining pregnancies did not receive any SRTH-targeting drug treatment. Pregnancy outcomes: Except for stillbirth in the first pregnancy of patient 7, preterm birth in patient 2 and the second pregnancy of patient 14, and no reported pregnancy outcomes in four cases (patients 6, 9-11), all other pregnancies had good outcomes. Neonatal thyroid function: Except for elevated serum TSH levels in newborns delivered by patient 7 in the second pregnancy, patient 14 in their first and second pregnancies and patients 16 and 17, and no reported thyroid function in newborns delivered by patients 6, 9-11, and the first pregnancy of patient 7, all other newborns had normal thyroid function.

Pregnant woman with SRTH is relatively rare, and its pathogenesis is not yet clear, but often accompanied by THRβ gene abnormalities. For pregnant women with suspected SRTH, thorough medical history collection combined with auxiliary examinations is required to guide individualized targeted treatment. Regular prenatal surveillance is essential for dynamic disease assessment throughout gestation of SRTH pregnant woman. Postpartum comprehensive thyroid function screening should be completed for all neonates born to mothers with SRTH.