Ageing and pituitary neuroendocrine tumours (PitNETs): from bench to bedside.

Abstract: The prevalence of pituitary neuroendocrine tumours (PitNETs) in elderly people (≥65 years old) is raising with life expectancy. Despite an increasing incidental detection on neuroimaging for unrelated conditions, a large majority are macrotumours (≥1 cm) and mass effects are frequent, in particular visual defects. Clinically non-functioning PitNETs are the most prevalent (about 75%), and a majority are gonadotrophs. The clinical presentation of functioning PitNETs differ from younger patients and include somatotroph tumours - often intrasellar with mild acromegaly, prolactinomas - often large and invasive, and rare corticotroph and uncommon thyrotroph tumours. Such epidemiological characteristics likely reflect different biological features as compared with PitNETs diagnosed in younger patients. Epigenetic alterations are more frequent than mutations, whereas cell senescence and age-related changes in immune surveillance and feedback mechanisms from ageing target organs may play an underestimated role. Endocrinological changes associated with ageing and concomitant pathological conditions should be considered as relevant confounding factors for diagnosis. In particular, ocular diseases may mask visual defects, progressive symptoms of hypopituitarism may be misinterpreted as ageing, and peripheral physiological (menopause) or pathological dysfunction or drugs given for other diseases can alter pituitary hormone secretion. Mild hypersecretion should be searched for in clinically non-functioning cases, as it may significantly impact on clinical management. Multidisciplinary evaluation is necessary to define personalized therapeutic goals, and where indicated, surgery should be performed by experienced pituitary surgeons. The development of innovative diagnostic and prognostic markers would usefully support the clinical management and follow-up of PitNETs in elderly patients.