Natural History of Non-Functioning Pituitary Adenomas: A Systematic
                    Review and Meta-Analysis

Stefan Dukanovic Rikvold; Mathias Brown Pedersen; Mikkel Andreassen; Jesper Krogh

doi:10.1055/a-2096-1340

Hormone and Metabolic Research, Inhaltsverzeichnis

Horm Metab Res 2023; 55(07): 443-451
DOI: 10.1055/a-2096-1340

Original Article: Endocrine Care

Natural History of Non-Functioning Pituitary Adenomas: A Systematic Review and Meta-Analysis

Stefan Dukanovic Rikvold

¹Department of Endocrinology and Metabolism, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

,

Mathias Brown Pedersen

¹Department of Endocrinology and Metabolism, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

,

Mikkel Andreassen

¹Department of Endocrinology and Metabolism, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark

,

Jesper Krogh

²Department of Medicine, Clinic for Pituitary Disorders, Zealand University Hospital – Koge, Denmark

› Institutsangaben

Abstract

The management of non-functioning pituitary tumors (NFPTs) relies on the risk of tumor growth and new endocrinopathies. The objective of this systematic review was to assess the risk of growth, new pituitary endocrinopathies, and surgery in patients with conservatively treated NFPTs. We conducted a bibliographical search identifying studies assessing NFPTs followed conservatively. Estimates were pooled using random-effects meta-analysis reporting events per 100 person years (PYs), in case of high heterogeneity (I2>75%) only the range of observed effects was reported. We identified 30 cohort studies including 1957 patients with a mean follow-up time of 4.0 (SD 1.5) years. The overall risk of tumor growth ranged from 0.0 to 14.2/100 PYs (I2=90%), while the overall risk of new endocrinopathies was 0.9/100 PYs (95% CI. 0.5 to 1.2; I2=35%) and risk of surgery ranged from 0.0 to 7.7/100 PYs (I2=80%). Compared to microadenomas, macroadenomas had higher risk of growth (p=0.002), higher risk of surgery (p=0.006), and non-significant differences in risk of new endocrinopathies (p=0.15). An analysis of microadenomas found the risk of growth to be 1.8/100 PYs (95% CI. 0.9 to 2.8; I2=58%), the risk of new endocrinopathies 0.7/100 PYs (95% CI. 0.0 to 1.6; I2=37%) and the risk of surgery 0.5/100 PYs (0.1 to 0.9; I2=37%). These data support individualized follow-up strategies of patients with NFPTs and particularly a less rigorous follow-up of patients with microadenomas.

Key words

non-functioning pituitary tumors - PitNets - natural history - endocrinopathies

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Referenzen

References
1 Fernández-Balsells MM, Murad MH, Barwise A. et al. Natural history of nonfunctioning pituitary adenomas and incidentalomas: a systematic review and metaanalysis. J Clin Endocrinol Metab 2011; 96: 905-912
2 Aghi MK, Chen CC, Fleseriu M. et al. Congress of neurological surgeons systematic review and evidence-based guidelines on the management of patients with nonfunctioning pituitary adenomas: executive summary. Neurosurgery 2016; 79: 521-523
3 Pedersen MB, Dukanovic S, Springborg JB. et al. Endocrine function after transsphenoidal surgery in patients with non-functioning pituitary adenomas: a systematic review and meta-analysis. Neuroendocrinology 2022; 112: 823-834
4 Kim JH, Dho YS, Kim YH. et al. Developing an optimal follow-up strategy based on the natural history of nonfunctioning pituitary adenomas. J Neurosurg 2018; 131: 500-506
5 Tresoldi AS, Carosi G, Betella N. et al. Clinically nonfunctioning pituitary incidentalomas: characteristics and natural history. Neuroendocrinology 2020; 110: 595-603
6 Osamura RY, Grossman A, Kontogeorgos G. et al. Introduction. WHO Classification of Tumors in Endocrine Organs, 4th ed., Vol. 10; Lloyd RV, Osamura RY, Klöppel G, Rosai J (eds). WHO; 2017
7 Liu J, He Y, Zhang X. et al. Clinicopathological analysis of 250 cases of pituitary adenoma under the new WHO classification. Oncol Lett 2020; 19: 1890-1898
8 Lenders NF, Wilkinson AC, Wong SJ. et al. Transcription factor immunohistochemistry in the diagnosis of pituitary tumors. Eur J Endocrinol 2021; 184: 891-901
9 Pereira AM, Biermasz NR. Treatment of nonfunctioning pituitary adenomas: What were the contributions of the last 10 years? A critical view. Ann Endocrinol 2012; 73: 111-116
10 Pernik MN, Montgomery EY, Isa S. et al. The natural history of non-functioning pituitary adenomas: a meta-analysis of conservatively managed tumors. J Clin Neurosci 2022; 95: 134-141
11 Han AJ, Varlamov EV, Fleseriu M.. Nonfunctioning pituitary microadenomas: should imaging interval be extended? A large single-center cohort study. J Clin Endocrinol Metab 2022; 107: e1231-e1241
12 Thaker VV, Lage AE, Kumari G. et al. Clinical course of nonfunctional pituitary microadenoma in children: a single-center experience. J Clin Endocrinol Metab 2019; 104: 5906-5912
13 Hozo SP, Djulbegovic B, Hozo I.. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 2005; 5: 13
14 Reincke M, Allolio B, Saeger W. et al. The 'incidentaloma' of the pituitary gland. Is neurosurgery required?. JAMA 1990; 263: 2772-2776
15 Donovan LE, Corenblum B.. The natural history of the pituitary incidentaloma. Archiv Intern Med 1995; 155: 181-183
16 Nishizawa S, Ohta S, Yokoyama T. et al. Therapeutic strategy for incidentally found pituitary tumors ('Pituitary incidentalomas'). Neurosurgery 1998; 43: 1344-1350
17 Feldkamp J, Santen R, Harms E. et al. Incidentally discovered pituitary lesions: High frequency of macroadenomas and hormone-secreting adenomas – Results of a prospective study. Clin Endocrinol 1999; 51: 109-113
18 Igarashi T, Saeki N, Yamaura A.. Long-term magnetic resonance imaging follow-up of asymptomatic sellar tumors & mdash. their natural history and surgical indications & mdash. Neurol Med Chirurg 1999; 39: 592-599
19 Oyama K, Sanno N, Tahara S. et al. Management of pituitary incidentalomas: according to a survey of pituitary incidentalomas in Japan. Semin Ultrasound CT MR 2005; 26: 47-50
20 Vilar L, Azevedo MF, Barisic G. et al. Pituitary incidentalomas. Arq Bras Endocrinol Metabol 2005; 49: 651-656
21 Arita K, Tominaga A, Sugiyama K. et al. Natural course of incidentally found nonfunctioning pituitary adenoma, with special reference to pituitary apoplexy during follow-up examination. J Neurosurg 2006; 104: 884-891
22 Dekkers OM, Hammer S, de Keizer RJW. et al. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol 2007; 156: 217-224
23 Karavitaki N, Collison K, Halliday J. et al. What is the natural history of nonoperated nonfunctioning pituitary adenomas?. Clin Endocrinol 2007; 67: 938-943
24 Carsote M, Chirita C, Dumitrascu A. et al. Pituitary incidentalomas--how often is too often?. J Med Life 2009; 2: 92-97
25 Cury ML, Fernandes JC, Machado HR. et al. Non-functioning pituitary adenomas: clinical feature, laboratorial and imaging assessment, therapeutic management and outcome. Arq Bras Endocrinol Metabol 2009; 53: 31-39
26 Ryu WHA, Tam S, Rotenberg B. et al. Conservative management of pituitary macroadenoma contacting the optic apparatus. Canad J Neurol Sci 2010; 37: 837-842
27 Anagnostis P, Adamidou F, Polyzos SA. et al. Non-functioning pituitary adenomas: A single center experience. Exp Clin Endocrinol Diabetes 2011; 119: 314-319
28 de Laat JM, Dekkers OM, Pieterman CR. et al. Long-term natural course of pituitary tumors in patients with MEN1: Results from the dutchmen1 study group (DMSG). Transl Endocrinol Metab 2015; 100: 3288-3296
29 Karamouzis I, Berardelli R, Prencipe N. et al. Retrospective observational analysis of non-irradiated non-functioning pituitary adenomas. J Endocrinol Invest 2015; 38: 1191-1197
30 Sam AH, Shah S, Saleh K. et al. Clinical outcomes in patients with nonfunctioning pituitary adenomas managed conservatively. Clin Endocrinol 2015; 83: 861-865
31 Vargas G, Gonzalez B, Ramirez C. et al. Clinical characteristics and treatment outcome of 485 patients with nonfunctioning pituitary macroadenomas. Int J Endocrinol 2015; 756069
32 Imran SA, Yip CE, Papneja N. et al. Analysis and natural history of pituitary incidentalomas. Eu J Endocrinol 2016; 175: 1-9
33 Lenders N, Ikeuchi S, Russell AW. et al. Longitudinal evaluation of the natural history of conservatively managed nonfunctioning pituitary adenomas. Clin Endocrinol 2016; 84: 222-228
34 Iglesias P, Arcano K, Trivino V. et al. Prevalence, clinical features, and natural history of incidental clinically non-functioning pituitary adenomas. Horm Metab Res 2017; 49: 654-659
35 Levy MJ, Robertson IJ, Khalk N. et al. Long-term follow-up of a large prospective cohort of patients with nonfunctioning pituitary adenomas: The outcome of a conservative management policy. Clin Endocrinol 2018; 89: 354-359
36 Stalldecker G, Ballarino C, Diez S. et al. Pituitary adenomas in elderly patients. Medicina (Argentina) 2019; 79: 191-196
37 Wu Y, Gao L, Guo X. et al. Pituitary adenomas in patients with multiple endocrine neoplasia type 1: a single-center experience in China. Pituitary 2019; 22: 113-123
38 Hwang K, Kim YH, Kim JH. et al. The outcomes of conservatively observed asymptomatic nonfunctioning pituitary adenomas with optic nerve compression. J Neurosurg 2020; 1-8
39 Borghammar C, Tamaddon A, Erfurth EM. et al. Non-functioning pituitary microadenoma in children and adolescents: Is follow-up with diagnostic imaging necessary?. Endocrine 2023; 79: 152-160
40 Freda PU, Beckers AM, Katznelson L. et al. Pituitary incidentaloma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 894-904

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