下垂体炎是一种罕见的下垂体炎症性疾患，近年来报道的病例有所增加。我们的目标是总结关于原发性和继发性下垂体炎的病因发病机制、分子机制和遗传学的最新研究。原发性自身免疫性下垂体炎（PAH）：在疾病的急性期，由于T淋巴细胞和B淋巴细胞的浸润，垂体腺肿大。慢性期的特点是逐渐进行性和不可逆的垂体萎缩。APA可能在PAH的管理、诊断和预后中起到一定作用。已在患有下垂体炎和下垂体功能减退症的患者中发现特异性自身抗体，如抗生长激素抗体、抗-PIT-1抗体和抗T-PIT抗体。一项最新研究建议，逃脱克隆删除机制并对自身抗原进行免疫应答的机制可以解释PAH患者观察到的异常免疫应答的特殊性质。细胞因子阵列显示存在γ干扰素和白细胞介素-17。携带PIT1基因或PROP1基因突变的患者可能表现为PAH。携带HLA DQ8单倍型的个体患PAH的风险是没有携带这种单倍型的个体的四倍。免疫检查点抑制剂引起下垂体炎（IIHs）：IIHs是治疗靶向细胞毒性T淋巴细胞抗原4（CTLA-4）和程序性细胞死亡因子1（PD-1）抑制剂的患者中不断增加的毒性反应。ICI抑制CTLA-4途径导致T淋巴细胞过度活化。PD-1/PD-L1的结合抑制T细胞的活性，促进T辅助细胞转化为T调节细胞，并激活癌细胞的促生存信号通路。细胞因子在IIHs中起着重要作用。已观察到B细胞浸润可能提示抗体介导的垂体损伤可能对此有所贡献。CTLA-4和PD-1基因的遗传多态性可能增加IIHs的风险。 HLA基因等位基因可能也参与了IIHs的发生，这种HLA关联性提供了一种可能的另类机制假说。IIHs也可能与由垂体特异性抗原异位表达引发的副肿瘤综合征相关。与SARS-CoV-2相关的下垂体炎：最近的文献报道了与SARS-CoV-2病毒相关的下垂体炎的发生；长期COVID-19也可能表现为漏斗神经下垂体炎。由于其与血管紧张素转换酶受体的特殊相互作用，病毒进入中枢神经系统，通过尖刺蛋白结合毛细血管内皮细胞造成直接损伤。 SARS-CoV-2的影响可能通过炎症和细胞因子的释放间接发生。确切的机制尚不明确。目前关于SARS-CoV-2疫苗相关的内分泌并发症的可用数据很少。尽管如此，已有个别下垂体炎病例的记录。下垂体炎的治疗：糖皮质激素是管理原发性下垂体炎的基石，因为其针对炎症的有针对性作用。更好地了解下垂体炎的病因发病机制可以导致更有效和个体化的治疗策略。

Hypophysitis, a rare inflammatory disorder of the pituitary gland, has seen an uptick in reported cases in recent years. Our objective is to summarize the most recent research on the etiopathogenesis, molecular mechanisms, and genetics of both primary and secondary hypophysitis. Primary autoimmune hypophysitis (PAH): During the acute phase of the disease, the pituitary gland in enlarged due to the infiltration of T and B lymphocytes. The chronic phase is characterized by progressive and irreversible pituitary atrophy. APA may play a role in the management, diagnosis, and prognosis of PAH. Specific autoantibodies such as anti-GH, anti-PIT-1, and anti-T-PIT have been found in patients with hypophysitis and hypopituitarism. A recent study suggested that a mechanism of escaping clonal deletion and mounting an immune response against self antigens can explain the unusual nature of the immune response observed in PAH patients. A cytokine array shows the presence of gamma-interferon and interleukin-17. Patients carrying mutations in the PIT1 or PROP1 genes may present PAH. Individuals carrying the HLA DQ8 haplotype are four times more likely to develop PAH. Immune checkpoint inhibitors induce hypophysitis (IIHs): IIHs is an increasingly frequent toxicity of in patients on treatment with inhibitors targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). ICIs inhibit the CTLA-4 pathway, leading to overactivation of T lymphocytes. The binding of PD-1/PD-L1 suppresses the activity of T cells, promotes the conversion of T-helpers into T-regulatory cells, and activates pro-survival signaling pathways in cancer cells. Cytokines play a crucial role in IIHs. B-cell infiltration has been observed in IIHs, suggesting that antibody-mediated pituitary injury may contribute. Genetic polymorphisms of CTLA-4 and PD-1 genes can increase the risk of IIHs. HLA alleles may also be involved in the onset of IIHs; this HLA association presents a possible alternative mechanistic hypothesis. IIHs may also be linked to a paraneoplastic syndrome triggered by ectopic expression of pituitary specific antigens. SARS-CoV-2-related hypophysitis: Recently, the literature has reported occurrences of hypophysitis associated with the SARS-CoV-2 virus; long COVID-19 may also present as infundibulo-neuro-hypophysitis. The virus enters the central nervous system because of its distinct interaction with angiotensin-converting enzyme receptors via spike proteins binding the capillary endothelium, and it directly damages the pituitary cells. The effect of SARS-CoV-2 can occur indirectly through inflammation and the release of cytokines. The exact mechanism remains ambiguous. The available data on endocrine complications associated with the SARS-CoV-2 vaccine are scant. Nonetheless, isolated cases of hypophysitis have been documented. Treatment of hypophysitis: Glucocorticoids are the cornerstone in managing primary hypophysitis, given their targeted action on inflammation. A better understanding of the etiopathogenesis and molecular mechanism of hypophysitis can lead to more effective and personalized treatment strategies.