Endocrinol Metab.  2023 Dec;38(6):631-654. 10.3803/EnM.2023.1838.

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

• Whyte E
• Nezu M
• Chik C
• Tateno T

• KMID: 2549257
• DOI: http://doi.org/10.3803/EnM.2023.1838

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.

Keyword

Non-functioning pituitary neuroendocrine tumors; Biomarkers; Medical treatment; Pituitary surgery; Endocrine care

Figure

• 

  Fig. 1. Knosp classification and modified Knosp classification. Knosp classification divides tumors into five categories ranging from grade 0 to grade 4 according to the tumor extension to three types of boundaries: medial tangent (short black dotted line), intercarotid line (long black dotted line), and lateral tangent (black straight line). Grade 0: tumor remains medial to the medial tangent. Grade 1: tumor extends to between the medial tangent and the intercarotid line. Grade 2: tumor extends to between the intercarotid line and the lateral tangent. Grade 3: tumor extends lateral to the lateral tangent. Grade 4: complete encasement of intracavernous internal carotid artery (ICA). In the modified Knosp classification, Grade 3 is further divided into two groups according to the direction of tumor extension. Grade 3A: tumor extends above the intracavernous ICA into the superior cavernous sinus (CS) compartment. Grade 3B: tumor extends below the intracavernous ICA into the inferior CS compartment. OC, optic chiasm; PIT, pituitary gland; PitNET, pituitary neuroendocrine tumor.

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