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免疫检查点抑制剂治疗后诊断的抗垂体特异性转录因子-1 性垂体炎的早期临床病程:一例病例并文献复习。

The early-stage clinical course of anti-pituitary-specific transcription factor-1 hypophysitis diagnosed post-immune checkpoint inhibitor treatment: A case with review of literature.

机构信息

Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.

Department of Diabetes and Endocrinology, Hyogo Cancer Center, Akashi, Japan.

出版信息

J Neuroendocrinol. 2024 Jun;36(6):e13395. doi: 10.1111/jne.13395. Epub 2024 Apr 17.

DOI:10.1111/jne.13395
PMID:38631695
Abstract

Anti-pituitary-specific transcription factor-1 (PIT-1) hypophysitis, a paraneoplastic syndrome resulting from an autoimmune response against PIT-1, typically manifests with undetectable levels of growth hormone (GH) and prolactin (PRL), and significantly low levels of serum thyroid-stimulating hormone (TSH) at diagnosis. These hormonal levels are highly specific to this disease and serve as key diagnostic indicators. Herein, we present a detailed clinical course of a 69-year-old male with a history of gastric cancer and lymph node metastases who developed anti-PIT-1 hypophysitis after the initiation of immune checkpoint inhibitor (ICI) therapy, specifically nivolumab, oxaliplatin, and capecitabine. The patient was referred to our department owing to decreased TSH, free triiodothyronine (T3), and free thyroxine (T4) levels after two doses of nivolumab. Initially suspected as central hypothyroidism due to ICI-related hypophysitis, further assessment confirmed the diagnosis of anti-PIT-1 hypophysitis. Notably, GH, PRL, and TSH levels markedly declined, leading to complete deficiencies 2 months after the first nivolumab dose-a pattern consistent with that of previous cases of anti-PIT-1 hypophysitis. Therefore, this report not only presents an atypical subset of ICI-related hypophysitis but also delineates the process of hormone impairment leading to complete deficiencies in anti-PIT-1 hypophysitis. This case highlights the importance of vigilant monitoring for endocrine issues in patients undergoing ICI therapy, given the escalating incidence of immune-related adverse events associated with the extensive use of ICI therapy for various cancers.

摘要

抗垂体特异性转录因子-1(PIT-1)性垂体炎是一种由针对 PIT-1 的自身免疫反应引起的副瘤综合征,其典型表现为生长激素(GH)和催乳素(PRL)水平无法检测到,而血清促甲状腺激素(TSH)水平显著降低。这些激素水平对该疾病具有高度特异性,是关键的诊断指标。在此,我们报告了一例 69 岁男性的详细临床病程,该患者患有胃癌和淋巴结转移病史,在开始免疫检查点抑制剂(ICI)治疗后,特别是纳武单抗、奥沙利铂和卡培他滨治疗后,发生了抗 PIT-1 性垂体炎。该患者因接受两剂纳武单抗后 TSH、游离三碘甲状腺原氨酸(T3)和游离甲状腺素(T4)水平降低而被转至我科。最初由于 ICI 相关垂体炎而怀疑为中枢性甲状腺功能减退症,但进一步评估确诊为抗 PIT-1 性垂体炎。值得注意的是,GH、PRL 和 TSH 水平明显下降,在首次接受纳武单抗治疗后 2 个月内导致完全缺乏,这与之前抗 PIT-1 性垂体炎的病例一致。因此,本报告不仅介绍了 ICI 相关垂体炎的一个非典型亚组,还阐述了导致抗 PIT-1 性垂体炎完全缺乏的激素损伤过程。该病例强调了在接受 ICI 治疗的患者中密切监测内分泌问题的重要性,因为随着 ICI 治疗在各种癌症中的广泛应用,免疫相关不良事件的发生率不断上升。

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引用本文的文献

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Endocr J. 2025 Jun 2;72(6):649-662. doi: 10.1507/endocrj.EJ25-0035. Epub 2025 Mar 27.
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Anti-PIT1 hypophysitis after immune checkpoint inhibitor treatment.免疫检查点抑制剂治疗后发生的抗PIT1垂体炎
Nat Rev Endocrinol. 2025 May;21(5):265-266. doi: 10.1038/s41574-025-01099-8.