, Volume 22, Issue 5, pp 520–531 | Cite as

Predictive modeling for pituitary adenomas: single center experience in 501 consecutive patients

  • A. L. PappyII
  • A. Savinkina
  • C. Bicknese
  • S. Neill
  • N. M. Oyesiku
  • A. G. IoachimescuEmail author



Personalized postoperative management of patients with pituitary adenomas requires an early risk stratification system.


We reviewed 501 cases operated between 10/27/2011 and 5/5/2016 by a single neurosurgeon. We determined biochemical remission and tumor resection at 3 months, and biochemical recurrence, tumor recurrence, radiation and reoperation during follow-up. We considered age, gender, tumor diameter, cavernous sinus invasion (CSI) by MRI, diagnostic category (clinical, biochemical and immunohistochemical), and proliferation markers in a Cox proportional hazards model. We built predictive models with the significant parameters and used Kaplan–Meier survival curves for time-dependent analyses.


The 501 cases comprised 141 functional and 360 nonfunctional adenomas. Tumor diameter, CSI, and ki-67 index predicted long-term events. Model 1 (CSI, diameter ≥ 2.9 cm and ki-67 > 3%) identified 18 (3.6%) adenomas and predicted persistent hypersecretory syndrome and residual tumor with 98.7% specificity (OR 8.6; CI 3.0–24.7). Model 2 (ki-67 > 3% and CSI) identified 48 (9.6%) adenomas and had 93.1% specificity (OR 3.3; CI 1.8–6.0). Model 3 (ki-67 > 3%, mitoses and p53, former “atypical” adenoma) identified 26 (5.2%) adenomas and had 96.0% specificity (OR 2.3; CI 1.0–5.0). Model 1 best predicted the long-term event-free survival and was strengthened when Knosp 3–4 CSI grades were used. Model 2 better identified the smaller adenomas at risk. Among the WHO 2017 special PA subtypes, patients with silent corticotroph adenoma had a lower event-free survival than ACTH-negative nonfunctional adenomas.


Use of CSI, ki-67 and tumor diameter in prediction models facilitates tailored surveillance and management of patients with pituitary adenomas.


Pituitary adenoma Cavernous sinus invasion Ki-67 Diameter Atypical adenoma Aggressive adenoma 



Cavernous sinus invasion


Positive predictive value


Negative predictive value


Standard deviation


Cushing’s disease




Non-functional adenoma


Silent ACTH-positive adenoma


Adrenocorticotropic hormone


Pituitary adenomas



Emilee Wehunt, research coordinator responsible for regulatory aspects pertaining to this study.

Compliance with ethical standards

Conflict of interest

The authors have nothing to disclose.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Emory’s institutional and/or national research committee.


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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Emory University School of MedicineAtlantaUSA
  2. 2.Emory Rollins School of Public HealthAtlantaUSA
  3. 3.Department of PathologyEmory University School of MedicineAtlantaUSA
  4. 4.Division of Endocrinology, Metabolism and Lipids, Department of MedicineEmory University School of MedicineAtlantaUSA
  5. 5.Department of NeurosurgeryEmory University School of MedicineAtlantaUSA

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