Hypothalamic–Pituitary Axis Involvement in Primary Central Nervous System Lymphoma: A Systematic Review

Context Primary central nervous system lymphoma (PCNSL) is a rare malignancy that may involve the hypothalamic–pituitary axis (HPA), leading to underrecognized but clinically significant endocrine dysfunction. Objective To characterize the spectrum and patterns of HPA-related endocrine disturbances in patients with PCNSL. Data Sources A systematic search was conducted in PubMed, EMBASE, Scopus, and Web of Science, supplemented by grey literature. The search concluded in February 2025. Study Selection We included studies reporting adult PCNSL cases with documented dysfunction of at least one hormonal axis. Exclusion criteria were pre-existing hypopituitarism or lack of endocrine data. Data Extraction Data on demographics, tumor localization, hormonal axes affected, radiological findings, treatment, and outcomes were extracted. Risk of bias was assessed using JBI tools. Results Ninety-nine cases met inclusion criteria. Diffuse large B-cell lymphoma (DLBCL) accounted for 84% of cases. Endocrine dysfunction included isolated adenohypophyseal involvement (46%), neurohypophyseal (8%), and combined (45%). The most affected pituitary axes were the gonadal and thyroid axes, with 89.7% and 89.2% involvement, respectively. Hypothalamic tumors were strongly associated with combined dysfunction (OR = 9.47, 95% CI: 3.76–23.86 p < 0.001). Persistent endocrinopathy was more frequent in progressive disease. No direct association was found between endocrine dysfunction and mortality. Conclusions HPA dysfunction in PCNSL is frequent and often underdiagnosed. Hypothalamic involvement is associated broader hormonal impairment. Routine hormonal screening and multidisciplinary management should be standard in PCNSL care to minimize complications and improve outcomes.