探讨甲状腺激素抵抗综合征(SRTH)孕妇的临床特点和诊治策略。

选择2023年11月在深圳市龙岗区妇幼保健院内科就诊的1例SRTH孕妇(孕妇1)为研究对象。采用回顾性分析方法，收集孕妇1的临床资料，对其临床表现、诊断及治疗过程进行分析、总结。以"甲状腺激素抵抗""孕妇""resistance to thyroid hormone in pregnancy"等为中、英文关键词，在中国知网数据库、万方数据知识服务平台及PubMed、Web of Science(WoS)数据库中检索SRTH孕妇相关研究文献，文献检索时限为2004年9月1日至2026年7月1日。对检索到的SRTH孕妇相关研究文献中关于SRTH孕妇的临床特点诊治策略进行综合分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。

①孕妇1为29岁初产妇，末次月经为2023年9月17日。因"甲状腺功能异常10^＋年"，2023年11月22日于本院内科门诊就诊。孕妇1在10^＋年前常规体检时发现甲状腺功能异常，当时无明显症状，未采取规范治疗，6年前，因甲状腺肿及明显高代谢症状伴血清游离甲状腺素(FT4)(又被称为游离四碘甲状腺原氨酸)升高，在外院被诊断为"甲状腺功能亢进"，采取¹³¹I治疗后，高代谢症状消失，无全身浮肿、畏寒等症状。2021年5月，曾在外院体检发现血清促甲状腺激素(TSH)及血清FT4、游离三碘甲状腺原氨酸(FT3)水平升高，垂体平扫与增强MRI结果均未见明显异常。2023年3月开始，在外院按照"¹³¹I治疗后甲状腺功能减退"，给予左甲状腺素(LT4) 50 μg/d治疗后血清TSH水平仍高，2023年11月将LT4剂量逐渐增加至175 μg/d后，血清TSH水平仅小幅度下降，并且导致血清FT4水平升高，故2023年12月停用LT4治疗，停药后血清FT4水平恢复正常。2024年3月，孕妇1的基因检测结果显示，其甲状腺激素受体β(THRβ)基因(chr3：24169098)存在c.1036C>T(p.Leu346Phe)变异(NM_001128177.1)，被确诊为SRTH患者。2024年6月，孕妇1于孕龄为39孕周时顺产1名男婴，分娩新生儿的甲状腺功能检查结果未见异常，甲状腺抗体略高。新生儿THRβ基因检测结果未发现THRβ基因突变；随访至1岁，生长发育良好，甲状腺功能正常。②文献复习共检索到3篇关于SRTH孕妇研究文献，涉及17例SRTH孕妇(孕妇2~18)，加上本研究孕妇1，共计18例孕妇被纳入进行以下综合分析。这18例孕妇共计23次单胎妊娠的孕期甲状腺功能特点：1例(孕妇1)为血清FT4与TSH水平同步升高，1例(孕妇2)为典型甲状腺功能亢进，1例(孕妇3)为甲状腺功能正常，1例(孕妇5)为早孕期血清FT4轻度升高，其余14例均为血清TSH水平正常、血清FT4水平升高。孕期SRTH处理措施：2例(孕妇10、12)孕期使用LT4治疗改善甲状腺功能减退症状，3例(孕妇2、15、18)使用丙硫氧嘧啶治疗甲状腺功能亢进，2例(孕妇7首次妊娠、孕妇17)使用甲巯咪唑抑制高FT4血症，3例(孕妇6、8、9)未报道孕期SRTH处理措施，其余孕期均未采取针对SRTH的药物治疗措施。妊娠结局：除孕妇7首次妊娠出现死胎，孕妇2与孕妇14第2次妊娠出现早产，4例(孕妇6、9~11)未报道妊娠结局外，其余均妊娠结局良好。新生儿甲状腺功能：除孕妇7第2次妊娠与孕妇14第1、2次妊娠及孕妇16、17分娩新生儿的血清TSH水平升高，5例(孕妇6、9~11及孕妇7首次妊娠)分娩新生儿未报道甲状腺功能外，其余新生儿甲状腺功能均正常。

SRTH孕妇临床上较为少见，发病机制迄今尚未阐明，多伴有THRβ基因异常。临床对此类孕妇应详细询问病史，并结合相关检查结果，按需治疗。对SRTH孕妇应定期产前检查，动态评估病情，分娩后应完善新生儿甲状腺功能等相关检查。

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.