Natural history of non-functioning pituitary microadenomas: results from the UK non-functioning pituitary adenoma consortium

Ross Hamblin, Athanasios Fountas, Kirstie Lithgow, Paul Benjamin Loughrey, Efstathios Bonanos, Shah Khalid Shinwari, Kirsten Mitchell, Syed Shah, Lydia Grixti, Mike Matheou, Kristina Isand, David S McLaren, Ashutosh Surya, Hafiz Zubair Ullah, Katarina Klaucane, Anuradha Jayasuriya, Sumbal Bhatti, Akash Mavilakandy, Masato Ahsan, Susan Mathew, Ziad Hussein, Thijs Jansz, Wunna Wunna, James MacFarlane, John Ayuk, Prakash Abraham, William M Drake, Mark Gurnell, Antonia Brooke, Stephanie E Baldeweg, Amir H Sam, Niamh Martin, Claire Higham, Narendra Reddy, Miles J Levy, Rupa Ahluwalia, John Newell-Price, Joannis Vamvakopoulos, Amutha Krishnan, Andrew Lansdown, Robert D Murray, Aparna Pal, Karin Bradley, Yaasir Mamoojee, Tejpal Purewal, Janki Panicker, E Marie Freel, Faisal Hasan, Mohit Kumar, Biju Jose, Steven J Hunter, Niki Karavitaki

The optimal approach to the surveillance of non-functioning pituitary microadenomas (micro-NFPAs) is not clearly established. Our aim was to generate evidence on the natural history of micro-NFPAs to support patient care. Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). Clinical, imaging, and hormonal data of micro-NFPA cases between 1/1/2008 and 21/12/2021 were analysed. Data for 459 patients were retrieved [median age at detection 44 years [interquartile range (IQR) 31-57) - 152 males/307 females]. 419 patients had more than two MRIs [median imaging monitoring 3.5 years (IQR 1.71-6.1)]. One case developed apoplexy. Cumulative probability of micro-NFPA growth was 7.8% (95%CI 4.9%-8.1%) and 14.5% (95%CI 10.2%-18.8%) at 3 and 5 years, respectively, and of reduction 14.1% (95%CI 10.4-17.8%) and 21.3% (95%CI 16.4-26.2%) at 3 and 5 years, respectively. Median tumour enlargement was 2 mm (IQR 1-3) and 49% of micro-NFPAs that grew became macroadenomas (nearly all >5 mm at detection). Eight (1.9%) patients received surgery (only one had visual compromise with surgery required >3 years after micro-NFPA detection). Sex, age, size at baseline were not predictors of enlargement/reduction. At time of detection, 7.2%, 1.7% and 1.5% patients had secondary hypogonadism, hypothyroidism and hypoadrenalism, respectively. Two (0.6%) developed hypopituitarism during follow-up (after progression to macroadenoma). Probability of micro-NFPA growth is low and development of new hypopituitarism is rare. Delaying first follow-up MRI to three years and avoiding hormonal re-evaluation in absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.