Redefining Pituitary Neuroendocrine Tumors in MEN1: Prevalence, Clinical Behavior, and Implications for Long-Term Surveillance

TL;DR

This study shows that pituitary tumors in MEN1 are common but mostly harmless, often requiring only careful monitoring rather than aggressive treatment.

Contribution

The study provides new insights into the prevalence and management of pituitary tumors in MEN1, advocating for personalized surveillance strategies.

Findings

Almost half of MEN1 patients developed pituitary tumors, mostly small and detected through screening.

Most tumors were managed with medication or monitoring, with surgery needed only for larger tumors.

Tumor recurrence was uncommon, and no sex-related differences were observed in outcomes.

Abstract

Multiple endocrine neoplasia type 1 is a rare inherited condition that causes tumors in several hormone-producing glands, including the pituitary gland. In this study, we analyzed pituitary tumors in over 100 patients followed at a single specialized center over two decades. Almost half of the patients developed a pituitary tumor, most often small lesions detected through regular screening. About half of the tumors produced excess hormones, mainly prolactin, while the others were hormonally inactive. Most tumors were successfully managed with medication or careful monitoring, and surgery was required only in a minority of cases, usually for larger tumors. Tumor recurrence was uncommon, and no meaningful differences were observed between men and women. Overall, our findings suggest that pituitary tumors in this condition are generally less aggressive than previously thought. These results support personalized follow-up strategies, with less intensive monitoring for inactive small tumors and closer surveillance for hormone-secreting ones.

Background: Pituitary neuroendocrine tumors (PitNETs) are a core manifestation of multiple endocrine neoplasia type 1 (MEN1), yet their true prevalence, biological behavior, and optimal management remain debated. Earlier reports suggested increased aggressiveness compared with sporadic PitNETs, while more recent surveillance-based studies indicate a predominantly indolent phenotype. Methods: We conducted a retrospective single-center study including all patients with clinical, familial, or genetic MEN1 referred to the Endocrinology Unit of the University of Naples “Federico II”, ENETS Center of Excellence, between January 2004 and June 2025. Demographic, clinical, radiological, hormonal, and therapeutic data were systematically collected. PitNETs were classified by size and hormonal activity. Results: Among 103 MEN1 patients (61 women), 50 (48.5%) were diagnosed with PitNETs at a mean age of 35.1 years. Microadenomas predominated (60%), and tumors were equally distributed between functioning and non-functioning lesions. Prolactin-secreting PitNETs were the most common functioning subtype (42%), followed by rare GH-, ACTH-, or mixed-secreting PitNETs. Dopamine agonists, mainly cabergoline, were prescribed in 38% of cases, while neurosurgical intervention was required in 14%, exclusively for macroadenomas. During follow-up, recurrence occurred in 8% of patients. No significant sex-related differences were observed in prevalence, tumor size, functional status, treatment approach, or outcomes. Conclusions: In our MEN1 cohort, PitNETs were frequent but largely indolent, with a predominance of microadenomas and limited need for surgery. Our findings support individualized, subtype-driven surveillance strategies, with conservative management for clinically non-functioning microadenomas and closer monitoring of prolactin-secreting PitNETs due to variable medical responsiveness.

Figures