Cell-lineage specific differences in presentation and outcomes of non-functioning pituitary adenomas – a multicentre study in patients seen at Endo-ERN reference centres 

Pituitary adenomas, also referred to as pituitary neuroendocrine tumours, are benign neoplasms of the anterior pituitary gland. Pituitary adenomas can be categorized into subtypes based on secretory status, phenotype, size, invasion, histopathological characteristics and proliferation index. In 2017, the evaluation of cell lineage-specific transcription factors (TFs) by immunohistochemistry (IHC) has been added to the World Health Organization (WHO) histopathological classification of pituitary neuroendocrine tumours (ENDO4) and this was maintained in the most recent WHO histopathological classification of 2022 (ENDO5). Studies have shown that the use of the cell lineage-specific TFs will identify the majority of IHC H- NFPAs as non-functioning gonadotroph or corticotroph adenomas. Studies based on IHC of adenohypophyseal hormones only showed heterogenous results of clinical behaviour in null cell adenomas (IHC H- NFPAs). 

Objective

The primary aim is to evaluate the associations between TF expression identified by IHC (exposure) and the radiological presentation, recurrence rates and therapeutic prognosis (outcome) in patients with non-functioning pituitary adenomas treated at an Endo-ERN Reference Centre who received surgery, and of whom pituitary tissue is available for analysis of cell lineage-specific TF expression patterns using immunohistochemistry (patients). 

The secondary aim is to evaluate associations between TF expression identified by IHC (exposure) and clinical presentation and prognosis (outcome) in patients with non-functioning pituitary adenomas treated at an Endo-ERN Reference Centre who received surgery, and of whom pituitary tissue is available for the analysis of cell lineage-specific TF expression patterns using immunohistochemistry (patients). 

Hypothesis

We hypothesize that that TPIT+ NFPAs and NCAs show the highest rate of invasion, have the greatest hazard on recurrence and undergo more interventions and postoperative radiotherapy compared to SF1+ and PIT1+ NFPAs. 

Data collection  

Longitudinal data will be collected at the following time points: at diagnosis, 2 years after diagnosis, 4 years after diagnosis, 5 years after diagnosis, 10 years after diagnosis, and in addition at the time of every intervention and 6 months after every intervention, and at the moment progression occurred that is not followed by an intervention.  

The presence of any of the pre-specified morbidities at the time of diagnosis is registered. During FU, study members are asked to register if an event has occurred, an if so, to specify the exact date of the event.  

A final assessment of the patient’s status will be made on 1 October 2026 of those patients who are still in FU.  

Standard operational procedures of the participating centers regarding the decision making between radiotherapy, repeat surgery or wait-and-scan approach in case of tumour regrowth will be explored due to expected heterogeneity in treatment strategies. 

References  

Van Der Hoeven, L. S., Slagboom, T. N. A., Malekzadeh, A., Hoogmoed, J., Drent, M. L., Aronica, E., Stenvers, D. J., & Pereira, A. M. (2025). Cell lineage-specific differences in clinical behaviour of non-functioning pituitary adenomas – A systematic review and meta-analysis. The Journal of Clinical Endocrinology & Metabolism.

Members of this Study Group

Initiating team 

Participating members