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, Kirstin Mitchell, Syed Adnan Alı 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 T 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 Levy, Rupa Ahluwalia, John Newell‐Price, Joannis Vamvakopoulos, Amutha Krishnan, Andrew Lansdown, Robert Murray, Aparna Pal, Karin Bradley, Yaasir Mamoojee, Tejpal Purewal, Janki Panicker, E. Marie Freel, Faisal Hasan, Mahesh Kumar, Biju Jose, Steven Hunter, Niki Karavitaki
Abstract
OBJECTIVE: 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. DESIGN: Multi-centre, retrospective, cohort study involving 23 endocrine departments (UK NFPA consortium). METHODS: Clinical, imaging, and hormonal data of micro-NFPA cases between January, 1, 2008 and December, 21, 2021 were analysed. RESULTS: Data for 459 patients were retrieved [median age at detection 44 years (IQR 31-57)-152 males/307 females]. Four hundred and nineteen patients had more than two magnetic resonance imagings (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, and size at baseline were not predictors of enlargement/reduction. At the 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). CONCLUSIONS: Probability of micro-NFPA growth is low, and the development of new hypopituitarism is rare. Delaying the first follow-up MRI to 3 years and avoiding hormonal re-evaluation in the absence of tumour growth or clinical manifestations is a safe approach for micro-NFPA surveillance.