分化型甲状腺癌术后不同TSH抑制水平对育龄女性患者 血清抗米勒管激素的影响

Influence of thyroid stimulating hormone suppression therapy after differentiated thyroid cancer surgery on serum anti-mullerian hormone level in women of childbearing age

摘要:

目的：分析育龄期女性分化型甲状腺癌（differentiated thyroid carcinoma，DTC）患者进行术后促甲状腺激素（thyroid stim－ulating hormone，TSH）抑制治疗期间，不同TSH抑制水平对其血清抗米勒管激素（anti-Müllerian hormone，AMH）的影响，探讨TSH抑制治疗对育龄女性卵巢储备是否存在负面干扰。方法：DTC研究对象来自吉林大学中日联谊医院DTC患者术后随访项目，选取其中20~48岁、未停经且规律接受左甲状腺素（levothyroxine，LT4）进行术后TSH抑制治疗超过3年的女性患者，记录其一般临床资料和月经史；采集静脉血、分离血清，化学发光免疫测定法检测其血清TSH、游离甲状腺素（free thyroxine，FT4）、游离三碘甲腺原氨酸（free triiodinethyronine，FT3）和AMH水平。健康对照组来自中国医科大学附属第一医院体检中心，既往身体健康，均为女性，按与DTC患者组年龄匹配选取；入选研究者收集其体检剩余血清检测TSH、FT4、FT3和AMH。结果：DTC术后TSH抑制治疗组（n=98）和健康对照组（n=40）研究对象年龄无统计学差异（P=0.89）；2组血清AMH水平分别为1.19（0.58~2.21） ng/mL和1.15（0.22~2.72） ng/mL，组间比较无明显统计学差异（P=0.89）。将DTC育龄女性患者按不同TSH抑制水平分为4个亚组：TSH<0.1 mIU/L组（n=26）、0.1 mIU/L ≤TSH<0.4 mIU/L组（n=23）、0.4 mIU/L≤TSH<2.0 mIU/L组（n=36）和TSH≥2.0 mIU/L组（n=13），各亚组与健康对照组研究对象的血清AMH水平分别为1.20（0.71~1.62）、1.01（0.57~2.22）、1.25（0.67~2.83）和0.92（0.10~2.81） ng/mL，差异没有统计学意义（P=0.58）。DTC患者血清AMH水平与TSH、FT4和FT3水平均无显著相关性（TSH：P=0.97；FT4：P=0.46；FT3：P=0.24，均P >0.05）。结论：作为反映卵巢储备的良好指标，血清AMH水平在DTC术后抑制治疗后与同年龄健康女性无明显差异，提示不同程度的TSH抑制治疗未影响育龄患者的卵巢储备即生育潜能。

Abstract:

Objective：To investigate the influence of postoperative thyroid stimulating hormone（TSH） suppression on serum anti-mul－lerian hormone（AMH） level in women of childbearing age with differentiated thyroid cancer（DTC），and to observe whether TSH sup－pression therapy has negative interference on ovarian reserve in women of childbearing age. Methods：The DTC subjects were selected from the patients enrolled in the postoperative follow-up pro－gram conducted by China-Japan Union Hospital of Jilin Uni－versity. The female patients，aged 20-48 years，who did not ex－perience menopause and regularly received levothyroxine（LT4） for postoperative TSH suppression for more than 3 years were enrolled，and their general clinical data and menstrual history were recorded. Venous blood samples were collected and serum was separated. Chemiluminescence immunoassay was used to measure the serum levels of TSH，free thyroxine（FT4），free triiodothyronine（FT3），and AMH. After being matched for age，healthy fe－male individuals who underwent physical examination in the Physical Examination Center in The First Affiliated Hospital of China Medical University were enrolled as healthy control group，and their serum samples were collected to measure the levels of TSH，FT4，FT3，and AMH. Results：There was no significant difference in age between postoperative TSH suppression group with 98 patients and healthy control group with 40 individuals. There was also no significant difference in serum AMH level [median（interquartile range）] between the two groups[1.19（0.58-2.21） ng/mL vs. 1.15（0.22-2.72） ng/mL），P=0.89]. The women of childbearing age with DTC were further divided into four subgroups according to the level of TSH suppression，i.e.，TSH<0.1 mIU/L group with 26 patients，0.1 mIU/L ≤TSH<0.4 mIU/L group with 23 patients，0.4 mIU/L≤TSH<2.0 mIU/L group with 36 patients，and TSH≥2.0 mIU/L group with 13 patients；the serum AMH levels in these subgroups were 1.20（0.71-1.62），1.01（0.57-2.22），1.25（0.67-2.83），and 0.92（0.10-2.81） ng/mL，respectively，and there was no significant difference in serum AMH level between these four subgroups and the healthy control group（P=0.58）. In the patients with DTC，serum AMH level was not correlated with TSH，FT4，and FT3 in TSH suppression patients（all P >0.05）. Conclusion：As a good indicator of ovarian reserve，serum AMH level shows no significant difference between women with DTC undergoing postoperative suppression therapy and healthy women of the same age，suggesting that TSH suppression therapy does not affect ovarian reserve，i.e.，reproductive potential，in DTC patients of childbearing age.