, Volume 63, Issue 2, pp 240–246 | Cite as

Clinical characteristics and surgical outcome in USP8-mutated human adrenocorticotropic hormone-secreting pituitary adenomas

  • Marco LosaEmail author
  • Pietro Mortini
  • Angela Pagnano
  • Mario Detomas
  • Maria Francesca Cassarino
  • Francesca Pecori Giraldi
Endocrine Surgery



somatic mutations in the ubiquitin-specific protease 8 (USP8) gene have recently been described in patients with Cushing’s disease (CD). The aim of the study is to verify whether USP8 mutation may predict early and late outcome of pituitary surgery in patients with CD operated at a single institution.


We performed a retrospective genetic analysis of 92 adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Specimens were screened for USP8 hotspot mutations in the exon 14 with Sanger sequencing. Hormonal and surgical data were compared between USP8 variant carriers and wild-type tumors.


USP8 variants were detected in 22 adenomas (23.9%) with higher prevalence in women (28.9% vs. 5.3% in men; p < 0.05). No significant difference in hormonal levels and tumoral features in relation to USP8 status was observed. Interestingly, USP8-variant carriers were more likely to achieve surgical remission than wild-type adenomas (100% vs. 75.7%; p = 0.01). Conversely, recurrence of CD occurred in 23% of USP8-mutated patients and in 13% of patients with wild-type adenoma. The recurrence-free survival did not differ significantly between the two groups (p = 0.42).


ACTH-secreting pituitary adenomas carrying somatic USP8 mutations are associated with a greater likelihood of surgical remission in patients operated by a single neurosurgeon. Recurrence rates are not related with USP8-variant status.


Pituitary neoplasms Pituitary surgery Adrenocorticotropin Cortisol 



This research did not receive any specific grant from any agency in the public, commercial or not-for-profit sector.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Pituitary Unit of the Division of Neurosurgery, IRCCS San RaffaeleUniversity Vita-SaluteMilanItaly
  2. 2.Istituto Auxologico Italiano IRCCSNeuroendocrine Research LaboratoryMilanItaly
  3. 3.Department of Clinical Sciences & Community HealthUniversity of MilanMilanItaly

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