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

Author:

Hamblin Ross123,Fountas Athanasios123,Lithgow Kirstie123,Loughrey Paul Benjamin45,Bonanos Efstathios4,Shinwari Shah Khalid6,Mitchell Kirsten7,Shah Syed8,Grixti Lydia9,Matheou Mike10,Isand Kristina10,McLaren David S11,Surya Ashutosh12,Ullah Hafiz Zubair12,Klaucane Katarina13,Jayasuriya Anuradha14,Bhatti Sumbal15,Mavilakandy Akash16,Ahsan Masato16,Mathew Susan17,Hussein Ziad18,Jansz Thijs19,Wunna Wunna20,MacFarlane James212223,Ayuk John23,Abraham Prakash24,Drake William M20,Gurnell Mark212223ORCID,Brooke Antonia19,Baldeweg Stephanie E18,Sam Amir H25,Martin Niamh25,Higham Claire1726,Reddy Narendra16,Levy Miles J16,Ahluwalia Rupa15,Newell-Price John1427,Vamvakopoulos Joannis13,Krishnan Amutha13,Lansdown Andrew12,Murray Robert D11ORCID,Pal Aparna10,Bradley Karin28,Mamoojee Yaasir9,Purewal Tejpal8,Panicker Janki8,Freel E Marie7,Hasan Faisal29,Kumar Mohit30,Jose Biju6,Hunter Steven J4,Karavitaki Niki123ORCID

Affiliation:

1. Institute of Metabolism and Systems Research, University of Birmingham , Birmingham, B15 2TT , United Kingdom

2. Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners , Birmingham, B15 2TT , United Kingdom

3. Department of Endocrinology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust , Birmingham, B15 2GW , United Kingdom

4. Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital , Belfast, BT12 6BA , United Kingdom

5. Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast , Belfast, BT9 7AE , United Kingdom

6. Department of Endocrinology and Metabolic Medicine, Royal Stoke University Hospital, University Hospitals of North Midlands , Stoke-on-Trent, ST4 6QE , United Kingdom

7. Department of Endocrinology, Queen Elizabeth University Hospital , Glasgow, G51 4TF , United Kingdom

8. Department of Endocrinology, Liverpool University Hospitals NHS Foundation Trust , Liverpool, L7 8YE , United Kingdom

9. Department of Endocrinology and Metabolic Medicine, The Newcastle-Upon-Tyne NHS Foundation Trust , Newcastle , NE7 7DN, United Kingdom

10. Department of Endocrinology, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford University Hospitals NHS Foundation Trust , Oxford, OX3 7LE , United Kingdom

11. Leeds Centre for Diabetes & Endocrinology, St James's University Hospital, Leeds Teaching Hospitals NHS Trust , Leeds , LS9 7TF, United Kingdom

12. Centre for Diabetes and Endocrinology, University Hospital of Wales , Cardiff, CF14 4XW , United Kingdom

13. Manx Centre for Endocrinology, Diabetes & Metabolism, Manx Care , Douglas, IM4 4RJ , Isle of Man

14. Department of Endocrinology and Metabolism, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust , Sheffield, S10 2JF , United Kingdom

15. Department of Endocrinology, Norfolk and Norwich University Hospitals Foundation Trust , Norwich, NR4 7UY , United Kingdom

16. Department of Endocrinology, Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust , Leicester, LE1 5WW , United Kingdom

17. Department of Endocrinology, The Christie NHS Foundation Trust , Manchester, M20 4BX , United Kingdom

18. Department of Diabetes & Endocrinology, University College London Hospital NHS Foundation Trust , London, NW1 2PG , United Kingdom

19. Department of Endocrinology and Metabolism, Royal Devon and Exeter NHS Foundation Trust , Exeter, EX2 5DW , United Kingdom

20. Department of Endocrinology, St Bartholomew's Hospital, Barts Health NHS Trust , London, EC1A 7BE , United Kingdom

21. Department of Endocrinology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust , Cambridge, CB2 0QQ , United Kingdom

22. Metabolic Research Laboratories, Wellcome MRC Institute of Metabolic Science, University of Cambridge , Cambridge, CB2 0QQ , United Kingdom

23. NIHR Cambridge Biomedical Research Centre, Addenbrooke's Hospital , Cambridge, CB2 0QQ , United Kingdom

24. Department of Diabetes and Endocrinology, Aberdeen Royal Infirmary , Aberdeen, AB25 2ZN , United Kingdom

25. Imperial Centre for Endocrinology, Imperial College Healthcare NHS Trust , London, W6 8RF , United Kingdom

26. Manchester Academic Health Science Centre, University of Manchester , Manchester, M13 9NQ , United Kingdom

27. Department of Oncology and Metabolism, University of Sheffield , Sheffield, S10 2RX , United Kingdom

28. Department of Diabetes and Endocrinology, Bristol Royal Infirmary, University Hospitals Bristol and Weston NHS Foundation Trust , Bristol, BS2 8HW , United Kingdom

29. Department of Diabetes and Endocrinology, Royal United Hospitals Bath NHS Foundation Trust , Bath, BA1 3NG , United Kingdom

30. Department of Endocrinology and Metabolic Medicine, Wrightington, Wigan and Leigh NHS Foundation Trust , Wigan, WN7 1HS , United Kingdom

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism

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