Update on Current Evidence for the Diagnosis and Management of Nonfunctioning Pituitary Neuroendocrine Tumors

Abstract

Pituitary neuroendocrine tumors (PitNETs) are the third most frequently diagnosed intracranial tumors, with nonfunctioning PitNETs (nfPitNETs) accounting for 30% of all pituitary tumors and representing the most common type of macroPitNETs. NfPitNETs are usually benign tumors with no evidence of hormone oversecretion except for hyperprolactinemia secondary to pituitary stalk compression. Due to this, they do not typically present with clinical syndromes like acromegaly, Cushing’s disease or hyperthyroidism and instead are identified incidentally on imaging or from symptoms of mass effects (headache, vision changes, apoplexy). With the lack of effective medical interventions, first-line treatment is transsphenoidal surgical resection, however, nfPitNETs often have supra- or parasellar extension, and total resection of the tumor is often not possible, resulting in residual tumor regrowth or reoccurrence. While functional PitNETs can be easily followed for recurrence using hormonal biomarkers, there is no similar parameter to predict recurrence in nfPitNETs, hence delaying early recognition and timely management. Therefore, there is a need to identify prognostic biomarkers that can be used for patient surveillance and as therapeutic targets. This review focuses on summarizing the current evidence on nfPitNETs, with a special focus on potential new biomarkers and therapeutics.

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“…Current treatment options for NFPAs include active surveillance, surgical resection, and radiotherapy . However, NFPAs usually have suprasaddle or parasphenoidal extensions; thus, it is hard to completely resect the tumor, leading to recurrence of tumor . Temozolomide (TMZ), an oral chemotherapeutic agent, which has been approved for the treatment of malignant gliomas, is gaining attention for the treatment of aggressive pituitary adenomas and carcinomas, prolactinomas, and adrenocorticotropic hormone-secreting tumors but is less effective for nonfunctioning tumors .…”

“…43 However, NFPAs usually have suprasaddle or parasphenoidal extensions; thus, it is hard to completely resect the tumor, leading to recurrence of tumor. 44 Temozolomide (TMZ), an oral chemotherapeutic agent, which has been approved for the treatment of malignant gliomas, 45 is gaining attention for the treatment of aggressive pituitary adenomas and carcinomas, prolactinomas, and adrenocorticotropic hormone-secreting tumors but is less effective for nonfunctioning tumors. 46 However, TMZ also has some side effects including fatigue, gastrointestinal discomfort nausea/ vomiting, and constipation.…”