Sex and Age Differences in Transcription Factor and Hormonal Immunostaining in Patients With Nonfunctioning Pituitary Adenomas

BACKGROUND AND OBJECTIVES: Nonfunctioning pituitary adenomas (NFPAs) have historically been characterized histologically based on hormonal immunostaining. The 2017 World Health Organization guidelines for pituitary neuroendocrine tumors further delineated NFPA classification based on biologically relevant transcription factors (TFs), including T-PIT, PIT-1, and steroidogenic factor 1 (SF-1). We sought to evaluate differences in NFPA immunohistochemistry (IHC) associated with biological sex and age according to new TF immunostaining criteria. METHODS: A retrospective review of data from a single institution was conducted to identify patients who had undergone NFPA resection from 2012 to 2023. Patients grouped based on their biological sex and then further divided into age categories. Univariable statistics were used to identify associations between patient demographics and NFPA IHC. RESULTS: A total of 416 patients were included in the IHC-hormone analysis, and 154 patients were included in the IHC-TF analysis. Men were significantly less likely to have NFPAs with positive immunostaining for T-PIT (odds ratio [OR] = 0.15, 95% CI: 0.06-0.37) or adrenocorticotropic hormone (OR = 0.38, 95% CI: 0.22-0.64) and significantly more likely to have NFPAs stain positive for SF-1 (OR = 4.87, 95% CI: 2.24-10.6), follicle-stimulating hormone (FSH) (OR = 2.46, 95% CI: 1.64-3.69), luteinizing hormone (OR = 2.28, 95% CI: 1.26-4.13), thyroid-stimulating hormone (OR = 2.56, 95% CI: 1.05-6.26), or the alpha subunit (OR = 2.01, 95% CI: 1.36-2.97). Compared with the youngest age group, women in the oldest age group were more likely to have an NFPA stain positive for SF-1 (OR = 6.88, 95% CI: 1.86-25.4), FSH (OR = 2.32, 95% CI: 1.02-5.27), or the alpha subunit (OR = 2.14, 95% CI: 1.02-4.47). Similarly, men in the oldest age group were more likely to have an NFPA staining positive for FSH (OR = 4.16, 95% CI: 1.90-9.11) and the alpha subunit (OR = 2.36, 95% CI: 1.10-5.05); they were less likely to have positive immunostaining for adrenocorticotropic hormone (OR = 0.19, 95% CI: 0.04-0.79). There were no age-related differences in TF staining for male patients. CONCLUSION: This study demonstrates that sex and age are important demographic factors associated with immunostaining patterns and TF lineage subtypes for NFPAs. Underlying endocrine factors dictated by age and sex may represent a role in tumorigenesis or progression of NFPAs.