成人下丘脑垂体区朗格汉斯细胞组织细胞增生症诊治——华山经验

Management of adult Langerhans cell histiocytosis in the hypothalamic-pituitary region—Experiences from Huashan Hospital

目的总结上海华山医院内分泌科成人下丘脑垂体区(hypothalamic-pituitary region, HPR)朗格汉斯细胞组织细胞增生症(Langerhans cell histiocytosis, LCH)的诊治经验。方法纳入2013年1月至2022年2月至我科确诊的成人LCH患者, 回顾性分析其临床特点及治疗反应。结果共纳入27例成人HPR-LCH患者, 下丘脑累及(H组)14例, 非下丘脑累及(NH组)13例。常见影像学表现为垂体柄增粗(25/27, 92.6%)。确诊时全垂体功能减退14例(51.9%), 代谢异常19例(70.4%)。H组肾上腺轴、甲状腺轴、全垂体功能减退及糖尿病比例均高于NH组(78.6%对23.1%;92.9%对30.8%;78.6%对23.1%;35.7%对0%;均P<0.050)。H组下丘脑综合征比例71.4%(10/14)。首次就诊确诊率79.2%(19/24), HPR及外周活检确诊率分别为48.1%和51.9%, 25.9%(7/27)多次活检确诊, 确诊时累及的外周病灶有骨、甲状腺、肺、淋巴结、胸腺、肝脏。20例化疗, 12周客观缓解率85%;4例局部治疗, 1例中医治疗, 1例放弃治疗, 1例失访。中位随访时间28(15, 54)个月, 期间H组死亡3例, NH组死亡1例。结论 HPR-LCH患者以中枢性尿崩症起病, 常伴垂体前叶功能减退、下丘脑综合征和代谢异常;磁共振成像(magnetic resonance imaging, MRI)提示垂体柄增粗或下丘脑病灶。HPR病灶常较小、诊断难度高, 全身评估寻找外周病灶有助于早活检早诊断。下丘脑累及者死亡率较高, 提示预后不良。

Objective To summarize experience of managing adult Langerhans cell histiocytosis(LCH)in hypothalamic-pituitary region(HPR)from Shanghai Huashan Hospital.Methods Adult HPR-LCH patients diagnosed at oar endocrinology department from January 2013 to February 2022 were included.Clinical characteristics and treatment response were retrospectively analyzed.Results A total of 27 adult HPR-LCH patients were included,with 14 cases involving the hypothalamus(H group)and 13 cases without(group NH).The common radiological findings included thickening of the pituitary stalk(25/27,92.6%).At the time of diagnosis,14 cases(51.9%)presented with panhypopituitarism,and 19 cases(70.4%)exhibited metabolic abnormalities.The group H had higher proportions of adrenal insufficiency,central hypothyroidism,panhypopituitarism,and diabetes compared to group NH(78.6%vs 23.1%;78.6%vs 23.1%;92.9%vs 30.8%,35.7%vs 0%,respectively,all P<0.05).Hypothalamus syndrome was identified in 71.4%(10/14)of group H.The inital diagnosis rate was 79.2%(19/24),with 48.1%and 51.9%through biopsy of sellar and extrasellar lesions,respectively.Repeated biopsies confirmed the diagnosis in 25.9%(7/27)of cases.The peripheral lesions included bone,thyroid,lung,lymph node,thymus and liver.Out of 20 cases treated with chemotherapy,the objective response rate was 85%at 12 weeks.Four cases received local therapy,one case received traditional Chinese medicine treatment,one case abandoned treatment,and one case was lost to follow-up.The median follow-up time was 28(range 15 to 54)months.During this period,there were 3 deaths in group H and 1 death in group NH.Conclusion Adult HPR-LCH patients presented with diabetes insipidus and high prevalences of hypopituitarism,hypothalamus syndrome and metabolic abnormalities.Typical imaging features were pituitary stalk thickening.A solitary mass in the HPR was usually very small,posing a great challenge for early diagnosis.Systemic evaluation would help to clarify the diagnosis.Patients with hypothalamus involvement had a higher mortality rate,suggesting the hypothalamus as a risk organ with poor prognosis.