The Clinical Usefulness of the PANOMEN 3 Grade Score

Pituitary adenomas, also referred to as pituitary neuroendocrine tumours, are, usually 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.

These subtypes differ substantially in clinical presentation and natural course. Subsequently, treatment strategies vary between these subtypes. Until recently, classification systems all (partly) incorporated histopathology. As a result, pituitary adenomas not requiring surgery could not be classified by any of these classification systems. The second Pituitary Neoplasm Nomenclature workshop (PANOMEN 2), initiated by the Pituitary Society, addressed the need for a comprehensive classification system that could guide prognosis and therapy of all pituitary adenomas.

The PANOMEN 3 clinical classification Workshop has proposed an all-inclusive classification system by integrating clinical, genetic, biochemical, radiological, pathological, and molecular data. Evidence-based risk factors that are associated with increased morbidity and mortality were included in the classification. A corrected score is calculated dependent on the amount of risk factors assessed and converted into a ranked grade of 0 to 3. These rank grades are hypothesized to be able to reflect disease severity together with a morbidity and mortality risk range.

Until now, this classification system has not been applied to a cohort of patients with pituitary adenomas, also not during the stage of conceptualization. Therefore, the discriminative potential together with the clinical usefulness of the system is yet unknown.  

Objective

The primary aim is to evaluate the clinical usefulness of the PANOMEN 3 Grade score in patients with all types of pituitary adenomas seen at Endo-ERN Reference Centers.  

The secondary aim is to assess the unadjusted and adjusted predictive values of the individual risk factors included in the PANOMEN 3 Grade score on tumour specific and general (co)morbidity in patients with all types of pituitary adenoma seen at Endo-ERN Reference Centers. 

Hypothesis

We hypothesize that the ranked PANOMEN Grade scores reflect a ranked association with (co)morbidities, where Grade score 3 results in the highest and Grade score 0 in the lowest prevalence of (co)morbidities.

Data collection  

Longitudinal data will be collected at the following disease time points: at diagnosis, 2 years after diagnosis, 4 years after diagnosis, 5 years after diagnosis, 10 years after diagnosis, at the time of an intervention and 6 months after an intervention, and (in case of progression not followed by any intervention) at the moment of progression.  

The presence of any of the predefined morbidities at the time of diagnosis is registered. During FU, study members are asked to register if an event has occurred, and 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.

Publications  

Ho KKY, Fleseriu M, Wass J, Katznelson L, Raverot G, Little AS, et al. A proposed clinical classification for pituitary neoplasms to guide therapy and prognosis. Lancet Diabetes Endocrinol. 2024;12(3):209-14.  

    Members of this Study Group

    Initiating Team 

    Name

    Expertise / Role

    Country

    Lead: Alberto Pereira endocrinologist, Endo-ERN Coordinator the Netherlands
    Dirk Jan Stenvers  endocrinologist the Netherlands
    Loren van der Hoeven  endocrinologist the Netherlands
    Jantien Hoogmoed Neurosurgeon the Netherlands
    Eleonora Aronica Pathologist the Netherlands

    Participating members

    Name Country
    Mai Christiansen Arlien-Søborg  Denmark
    Pietro Maffei  Italy
    Rosario Pivonello  Italy
    Alfonso Soto Moreno  Spain
    Johan de Graaf  the Netherlands
    Georgia Ntali  Greece
    Giovanna Mantovani  Italy 
    Anna Aulinas Maso  Spain
    Gerald Raverot  France
    Luis Antonio Castano Spain
    Nuria Valdes  Spain
    Camilla Schalin-Jäntti  Finland
    Federico Gatto  Italy
    Nienke Biermasz  the Netherlands 
    Iris Pelsma the Netherlands
    Natasha Appelman-Dijkstra  the Netherlands (EuRREB) 
    Faisal Ahmed the Netherlands (EuRREB) 
    Mariya Cherenko  the Netherlands (EuRREB) 
    Katharina Schilbach  Germany
    Savi Shishkov  Bulgaria
    Tobias Hallén  Sweden
    Daniele Esposito Sweden
    Carmen Georgescu  Romania
    Corina Andreescu  Belgium