Hypopituitarism in non-neuroendocrine pituitary tumors: a systematic review

The existing evidence on pituitary function impairment in non-neuroendocrine pituitary tumors (non-PitNETs) is limited and scattered. We performed a systematic review using PubMed, Embase, Scopus, and Cochrane of all reported studies that evaluated pituitary function in craniopharyngiomas, meningiomas, germinomas, pituitary lymphomas, pituicytomas, granular cell tumors, spindle cell oncocytomas, and pituitary metastases over the past 35 years. A total of 5,614 patients from 114 studies were analyzed. The weighted mean age was 35.01 ± 2.7 years (95% CI: 34.9-35.1) and 47.5 ± 14.1% (95% CI: 47.1-47.8) were women. The overall weighted proportion of hypopituitarism was 49.1 ± 24.2% (95% CI: 48.4-49.7) and arginine vasopressin deficiency (AVD) was 18.43 ± 16.6% (95% CI: 17.9-18.9). According to tumor type, prevalence of hypopituitarism was 67.3 ± 8.1% (95% CI: 66.5-68.9) for germinomas, 61.4 ± 20.8% (95% CI: 58.8-64.1) for metastases, 58.7 ± 22.2% (95% CI: 46.2-71.3) for lymphomas, 54.4 ± 30.8% (95% CI: 45.6-63.3) for pituicytomas, 53.8 ± 12.3% (95% CI: 47.5-59.8) for oncocytomas, 49.1 ± 17.2% (95% CI: 48.6-49.6) for craniopharyngiomas, 29.7 ± 16.6% (95% CI: 22.4-36.9) for granular cell tumors, and 11.5 ± 9.1% (95% CI: 10.8-12.3) for meningiomas. When comparing the most prevalent non-PitNETs, the weighted prevalence of hypopituitarism was higher in metastases compared to craniopharyngiomas (χ2 = 696.8, df = 1), p < 0.0001. Similarly, the weighted prevalence of hypopituitarism in craniopharyngiomas was higher compared to meningiomas (χ2 = 16,278.13, df = 1), p < 0.0001. In conclusion, non-PitNETs result in hypopituitarism in approximately half of the cases and AVD in nearly one-fifth. Pituitary metastases and craniopharyngiomas demonstrate greater local aggressiveness and a higher likelihood of disrupting hypothalamic-pituitary function compared to meningiomas.