Current opinion on the diagnosis and management of non-functioning pituitary adenomas

ABSTRACT

Introduction

Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment.

Areas covered

We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA.

Expert opinion

NFPA is a heterogeneous group of tumors, in respect to their origin and clinical course. In recent years, research on pathology and molecular biology have advanced our knowledge of NFPA pathogenesis. NFPA exhibit, in the majority of cases, an indolent behavior, with satisfactory response to treatment. In aggressive cases, multimodal management is needed; however, even this approach may be insufficient, so the development of new treatments is warranted for better management. In this setting, the understanding of the mechanisms involved in the genesis and progression of NFPA is crucial for the identification and development of directed treatments with higher chances of response.

KEYWORDS:

• Biomarkers
• immunohistochemistry
• molecular biology
• pituitary adenoma
• pangenomic classification
• who classification

Article highlights

• Non-functioning pituitary adenomas (NFPAs) are the second most common pituitary adenomas (PA) with no evidence of hormonal hypersecretion. Lack of clinical symptoms related to hormonal hypersecretion is associated with a delay in diagnosis.

• Mortality seems to be higher than that of general population, with tumor burden due to hypopituitarism and visual field defects perceived by the patients.

• NFPA.s may not necessarily be silent. It is possible that there is a continuum between totally functional and completely silent PA.

• NFPA of corticotrophic origin seemed to be more aggressive, but a recent systematic review showed that they do not have a higher risk of recurrence compared to other NFPA subtypes.

• Plurihormonal PIT-1 positive adenomas and silent Crooke cell adenomas seem to be aggressive NFPAs.

• Null cell adenomas are vanishingly rare with the introduction of transcription factors, with some authors questioning their existence.

• Somatic USP8 mutations and mutant K-RAS have been recently described in NFPA.

Declaration of interest

LE Wildemberg received speaker fees from Novartis and participated in the advisory board for Crinetics. MR Gadelha received speaker fees from Ipsen, Recordati Rare Diseases, and Crinetics and is a principal investigator in clinical trials from Crinetics and Recordati Rare Diseases and a member of the advisory board for Novartis, Ipsen, and Crinetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.