【目的】 探索晚期非小细胞肺癌（NSCLC）患者接受免疫检查点抑制剂（ICIs）治疗后出现甲状腺功能减退症（以下简称 “甲减”）的中医证候特点、证素分布与组合情况以及中医证型的分布规律。【方法】 选择2020年1月至2023年6月就诊于广州 中医药大学附属中山中医院，经病理确诊为ⅢB-ⅣB期、表皮生长因子受体/间变性淋巴瘤激酶（EGFR/ALK）阴性、并使用 ICIs治疗后出现甲减的NSCLC患者，共168例。收集患者的四诊信息，运用聚类分析总结出晚期NSCLC免疫治疗后出现甲减 的中医证候特点和证型分布规律，并对不同性别、年龄段和甲减分级的中医证型分布规律进行分析。【结果】（1）168例晚期 NSCLC 患者接受免疫治疗后出现甲减的中医证候以虚为主，表现为咳嗽、倦怠乏力、健忘、面色少华、自汗、皮肤干燥、 痰色白、懒言、头晕、夜尿多、视物模糊、形体消瘦、皮肤弹性差、纳呆恶食、嗜睡、长期食少、水肿、失眠、声低、隐 痛、指甲淡白、吐痰、经常畏冷、口渴、面色㿠白、喜温恶凉、渴欲热饮、气喘、经常便秘、大便干结、面睑浮肿、多梦、 腹胀、腰痛、排便无力等；舌脉象主要包括：舌苔薄白、舌淡红、舌边齿印、舌淡胖、舌淡、脉沉、脉滑、脉虚、尺脉弱、 脉细。（2）总体病位证素以肺、脾、肾多见，病性证素以气虚、阳虚、血虚、水停多见。（3）经聚类分析，得出以下3种证型， 分布频次由高到低依次为肺脾气虚证、肾阳亏虚证和气虚水停证。（4）不同年龄段的中医证型分布比较，差异有统计学意义 （P < 0.01）。其中，60 ~ 69岁患者以肺脾气虚为主要证型，≥ 70岁患者以肾阳亏虚为主要证型， < 50岁患者以气虚水停证为 主要证型。而不同性别、甲减等级的中医证型分布比较，差异均无统计学意义（P > 0.05）。【结论】 晚期NSCLC免疫治疗所致 甲减患者的中医证型以肺脾气虚、肾阳亏虚、气虚水停为主，正气亏虚是其变化、发展的主要病机。临床医师应及时关注 患者的症状变化，监测患者甲状腺功能指标，避免发生严重免疫治疗相关不良反应。

Objective To explore the characteristics of traditional Chinese medicine（TCM）syndrome，syndrome elements and their combination， and the distribution of TCM syndrome types in advanced non-small cell lung cancer（NSCLC）patients suffering from hypothyroidism after treatment with immune checkpoint inhibitors（ICIs）. Methods The analysis was conducted on 168 patients with NSCLC at stage Ⅲ B-Ⅳ B confirmed by pathological findings，whose epidermal growth factor receptor/anaplastic lymphoma kinase（EGFR/ALK）was negative，and then suffering from hypothyroidism aftertreatmentwithICIs from January 2020 to June 2023，who admitted to Zhongshan Hospital of Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine. The patients 􀆳 information collected by four diagnostic methods of TCM was analyzed， and then cluster analysis was used to explore the characteristics of TCM syndrome and the distribution of TCM syndrome types of immunotherapy-induced hypothyroidism in advanced NSCLC. Moreover， the distribution of TCM syndrome types in the patients with different genders， age groups， and hypothyroidism grades was analyzed. Results（1）The TCM syndrome of hypothyroidism appearing in 168 patients with advanced NSCLC after immunotherapy was characterized by deficiency type，which manifested as follows：cough，fatigue and weakness，amnesia，lusterless complexion， spontaneous sweating， dry skin， white sputum， unwilling to talk， dizziness， nocturnal polyuria， blurred vision，emaciation，poor skin elasticity，poor appetite or even anorexia，somnolence，long-term poor appetite， edema，insomnia，low voice，dull pain，light white color of fingernails，spitting，frequently intolerance of cold， thirst，bright pale complexion，preference of warmth and aversion to cold，thirst with preference of hot drink， dyspnea，frequent constipation，dry stools，puffiness of face and eyelid，dreaminess，abdominal fullness，lumbar pain，and weakness in defecation. The tongue manifestation and pulse condition were characterized by white and thin coating，pale-red tongue，tongue with tooth-marks，pale and enlarged tongue，pale tongue，deep pulse， slippery pulse， feeble pulse， weak cubital pulse， and thready pulse.（2） The disease - location syndrome elements usually involved in the lung，spleen，and kidney，and the disease-nature syndrome elements usually involved in qi deficiency，yang deficiency，blood deficiency，and water retention.（3）The cluster analysis yielded three syndrome types，and they were lung and spleen qi deficiency syndrome，kidney yang deficiency syndrome ， and qi deficiency and water retention syndrome in decreasing sequence of occurrence frequency.（4）Statistically significant difference of the distribution of TCM syndrome types was presented in the patients with various age groups（P < 0.01）. Lung and spleen qi deficiency syndrome was the main syndrome type in the patients aged 60 - 69 years old，kidney yang deficiency syndrome was frequently seen in the patients being or over 70 years old，and qi deficiency and water retention syndrome was frequently seen in the patients less than 50 years old. No statistically significant difference of the distribution of TCM syndrome types was presented in the patients with various genders and in the patients with various grades of hypothyroidism（P > 0.05）. Conclusion The immunotherapy-induced hypothyroidism in patients with advanced NSCLC is usually differentiated as the TCM syndrome types of lung-qi and spleen-qi deficiency，kidney yang deficiency，and qi deficiency and water retention. Deficiency of healthy qi contributes to the fundamental pathogenesis of the development and progression of the disease. Clinicians should pay attention to the changes of symptoms in time and monitor the thyroid function indicators of the patients，thus to avoid serious immunotherapy-related adverse events（irAEs）.

R273.342

广东省中医药局科研项目（编号：20231377）