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

Area of Science:

• Endocrinology
• Neurology
• Oncology

Background:

• Primary central nervous system lymphoma (PCNSL) is a rare cancer affecting the brain.
• PCNSL can impact the hypothalamic-pituitary axis (HPA), leading to significant endocrine issues.
• These endocrine dysfunctions are often overlooked in PCNSL patients.

Purpose of the Study:

• To systematically review and characterize endocrine disturbances related to the HPA in PCNSL patients.
• To identify patterns and specific hormonal axes most commonly affected by PCNSL.

Main Methods:

• Conducted a systematic literature search across major databases (PubMed, EMBASE, Scopus, Web of Science) up to February 2025.
• Included adult PCNSL cases with documented hormonal axis dysfunction, excluding pre-existing hypopituitarism.
• Extracted data on demographics, tumor location, affected axes, imaging, treatment, and outcomes; assessed risk of bias.

Main Results:

• Analyzed 99 PCNSL cases, with Diffuse Large B-cell Lymphoma (DLBCL) comprising 84%.
• Common dysfunctions included isolated adenohypophyseal (46%), neurohypophyseal (8%), and combined (45%) involvement.
• Gonadal (89.7%) and thyroid (89.2%) axes were most affected; hypothalamic tumors correlated with broader dysfunction (OR=9.47).

Conclusions:

• HPA dysfunction is a frequent and underdiagnosed complication of PCNSL.
• Hypothalamic involvement significantly broadens the spectrum of hormonal impairment.
• Routine hormonal screening and integrated, multidisciplinary care are essential for optimal PCNSL management.