Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis

V B Boesen; T H Hansen; M Motawea; M Fleseriu; E V Varlamov; A J Han; S A Imran; V Munro; M Alenazi; W J Inder; N Lenders; R A Damilano; N L Monteserin; A G Lania; G Carosi; G Mantovani; D Hordejuk; L Min; U B Kaiser; S D Rikvold; J Krogh

doi:10.1093/ejendo/lvaf189

Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis

V B Boesen, T H Hansen, M Motawea, M Fleseriu, E V Varlamov, A J Han, S A Imran, V Munro, M Alenazi, W J Inder, N Lenders, R A Damilano, N L Monteserin, A G Lania, G Carosi, G Mantovani, D Hordejuk, L Min, U B Kaiser, S D RikvoldJ Krogh^*

^*Corresponding author for this work

Department of Kidney and Hormone Diseases

2 Citations (Scopus)

Abstract

OBJECTIVE: Increased frequency of neuroimaging has led to enhanced identification of small nonfunctioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs.

DESIGN: A systematic review and individual participant data (IPD) meta-analysis.

METHODS: We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share IPD. Cohort studies including patients with conservatively treated micro-NFPAs with at least 1 follow-up magnetic resonance imaging were considered eligible. Fourteen studies met inclusion criteria. Six authors provided IPD (N = 647). Data were reanalyzed for verification. In cases of discrepancies the original authors were contacted for authentication.

RESULTS: Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the 2-step approach. Overall probability of surgery was 0.2/100 PYs (95% CI: 0.0-0.4; I2 = 28%). Probability of surgery due to visual impairment was 0.1/100 PYs (95% CI: 0.0-0.2; I2 = 0%). Both were independent of baseline tumor size (≥6 or <6 mm), sex, or age (P values >.40). Risk of developing a new endocrinopathy was 1.0/100 PYs (95% CI: 0.4-1.6; I2 = 0%). Data for classical meta-analysis were available for 7 studies (N = 1089) and supported the IPD results.

CONCLUSIONS: These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.

Original language	English
Journal	European Journal of Endocrinology
Volume	193
Issue number	4
Pages (from-to)	S61-S70
ISSN	0804-4643
DOIs	https://doi.org/10.1093/ejendo/lvaf189
Publication status	Published - 30 Sept 2025

Keywords

Adenoma/pathology
Humans
Pituitary Neoplasms/pathology
transsphenoidal surgery
pituitary adenoma
incidentaloma
hypopituitarism
pituitary insufficiency
vision loss
natural history

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10.1093/ejendo/lvaf189

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Boesen, V. B., Hansen, T. H., Motawea, M., Fleseriu, M., Varlamov, E. V., Han, A. J., Imran, S. A., Munro, V., Alenazi, M., Inder, W. J., Lenders, N., Damilano, R. A., Monteserin, N. L., Lania, A. G., Carosi, G., Mantovani, G., Hordejuk, D., Min, L., Kaiser, U. B., ... Krogh, J. (2025). Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis. European Journal of Endocrinology, 193(4), S61-S70. https://doi.org/10.1093/ejendo/lvaf189

Boesen, VB, Hansen, TH, Motawea, M, Fleseriu, M, Varlamov, EV, Han, AJ, Imran, SA, Munro, V, Alenazi, M, Inder, WJ, Lenders, N, Damilano, RA, Monteserin, NL, Lania, AG, Carosi, G, Mantovani, G, Hordejuk, D, Min, L, Kaiser, UB, Rikvold, SD & Krogh, J 2025, 'Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis', European Journal of Endocrinology, vol. 193, no. 4, pp. S61-S70. https://doi.org/10.1093/ejendo/lvaf189

@article{a0483ecc614f4393a6459c4502336f5d,

title = "Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis",

abstract = "OBJECTIVE: Increased frequency of neuroimaging has led to enhanced identification of small nonfunctioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs.DESIGN: A systematic review and individual participant data (IPD) meta-analysis.METHODS: We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share IPD. Cohort studies including patients with conservatively treated micro-NFPAs with at least 1 follow-up magnetic resonance imaging were considered eligible. Fourteen studies met inclusion criteria. Six authors provided IPD (N = 647). Data were reanalyzed for verification. In cases of discrepancies the original authors were contacted for authentication.RESULTS: Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the 2-step approach. Overall probability of surgery was 0.2/100 PYs (95\% CI: 0.0-0.4; I2 = 28\%). Probability of surgery due to visual impairment was 0.1/100 PYs (95\% CI: 0.0-0.2; I2 = 0\%). Both were independent of baseline tumor size (≥6 or <6 mm), sex, or age (P values >.40). Risk of developing a new endocrinopathy was 1.0/100 PYs (95\% CI: 0.4-1.6; I2 = 0\%). Data for classical meta-analysis were available for 7 studies (N = 1089) and supported the IPD results.CONCLUSIONS: These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.",

keywords = "Adenoma/pathology, Humans, Pituitary Neoplasms/pathology, transsphenoidal surgery, pituitary adenoma, incidentaloma, hypopituitarism, pituitary insufficiency, vision loss, natural history",

author = "Boesen, \{V B\} and Hansen, \{T H\} and M Motawea and M Fleseriu and Varlamov, \{E V\} and Han, \{A J\} and Imran, \{S A\} and V Munro and M Alenazi and Inder, \{W J\} and N Lenders and Damilano, \{R A\} and Monteserin, \{N L\} and Lania, \{A G\} and G Carosi and G Mantovani and D Hordejuk and L Min and Kaiser, \{U B\} and Rikvold, \{S D\} and J Krogh",

note = "{\textcopyright} The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].",

year = "2025",

month = sep,

day = "30",

doi = "10.1093/ejendo/lvaf189",

language = "English",

volume = "193",

pages = "S61--S70",

journal = "European Journal of Endocrinology",

issn = "0804-4643",

publisher = "BioScientifica Ltd.",

number = "4",

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TY - JOUR

T1 - Natural history of non-functioning pituitary microadenomas

T2 - a systematic review and individual participant data meta-analysis

AU - Boesen, V B

AU - Hansen, T H

AU - Motawea, M

AU - Fleseriu, M

AU - Varlamov, E V

AU - Han, A J

AU - Imran, S A

AU - Munro, V

AU - Alenazi, M

AU - Inder, W J

AU - Lenders, N

AU - Damilano, R A

AU - Monteserin, N L

AU - Lania, A G

AU - Carosi, G

AU - Mantovani, G

AU - Hordejuk, D

AU - Min, L

AU - Kaiser, U B

AU - Rikvold, S D

AU - Krogh, J

N1 - © The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact [email protected].

PY - 2025/9/30

Y1 - 2025/9/30

N2 - OBJECTIVE: Increased frequency of neuroimaging has led to enhanced identification of small nonfunctioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs.DESIGN: A systematic review and individual participant data (IPD) meta-analysis.METHODS: We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share IPD. Cohort studies including patients with conservatively treated micro-NFPAs with at least 1 follow-up magnetic resonance imaging were considered eligible. Fourteen studies met inclusion criteria. Six authors provided IPD (N = 647). Data were reanalyzed for verification. In cases of discrepancies the original authors were contacted for authentication.RESULTS: Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the 2-step approach. Overall probability of surgery was 0.2/100 PYs (95% CI: 0.0-0.4; I2 = 28%). Probability of surgery due to visual impairment was 0.1/100 PYs (95% CI: 0.0-0.2; I2 = 0%). Both were independent of baseline tumor size (≥6 or <6 mm), sex, or age (P values >.40). Risk of developing a new endocrinopathy was 1.0/100 PYs (95% CI: 0.4-1.6; I2 = 0%). Data for classical meta-analysis were available for 7 studies (N = 1089) and supported the IPD results.CONCLUSIONS: These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.

AB - OBJECTIVE: Increased frequency of neuroimaging has led to enhanced identification of small nonfunctioning pituitary adenomas (NFPAs) leading, in many cases, to extensive follow-up. However, the value of ongoing monitoring of these incidental lesions remains unclear. The study aims to determine the need for surgical intervention and assess the risks of developing new endocrinopathies during follow-up in patients with conservatively treated micro-NFPAs.DESIGN: A systematic review and individual participant data (IPD) meta-analysis.METHODS: We conducted a bibliographical search of PubMed and EMBASE to identify relevant studies. Authors of eligible studies were invited to share IPD. Cohort studies including patients with conservatively treated micro-NFPAs with at least 1 follow-up magnetic resonance imaging were considered eligible. Fourteen studies met inclusion criteria. Six authors provided IPD (N = 647). Data were reanalyzed for verification. In cases of discrepancies the original authors were contacted for authentication.RESULTS: Risk estimates were reported as number of events per 100 person-years (PYs). Estimates were pooled using the 2-step approach. Overall probability of surgery was 0.2/100 PYs (95% CI: 0.0-0.4; I2 = 28%). Probability of surgery due to visual impairment was 0.1/100 PYs (95% CI: 0.0-0.2; I2 = 0%). Both were independent of baseline tumor size (≥6 or <6 mm), sex, or age (P values >.40). Risk of developing a new endocrinopathy was 1.0/100 PYs (95% CI: 0.4-1.6; I2 = 0%). Data for classical meta-analysis were available for 7 studies (N = 1089) and supported the IPD results.CONCLUSIONS: These data suggest that routine follow-up of micro-NFPAs can be reduced significantly and that available guidelines should be revisited.

KW - Adenoma/pathology

KW - Humans

KW - Pituitary Neoplasms/pathology

KW - transsphenoidal surgery

KW - pituitary adenoma

KW - incidentaloma

KW - hypopituitarism

KW - pituitary insufficiency

KW - vision loss

KW - natural history

UR - https://www.scopus.com/pages/publications/105018709221

U2 - 10.1093/ejendo/lvaf189

DO - 10.1093/ejendo/lvaf189

M3 - Review

C2 - 40982460

SN - 0804-4643

VL - 193

SP - S61-S70

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 4

ER -

Natural history of non-functioning pituitary microadenomas: a systematic review and individual participant data meta-analysis

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