, Volume 15, Issue 3, pp 276–287 | Cite as

Temozolomide responsiveness in aggressive corticotroph tumours: a case report and review of the literature

  • A. K. Annamalai
  • A. F. Dean
  • N. Kandasamy
  • K. Kovacs
  • H. Burton
  • D. J. Halsall
  • A. S. Shaw
  • N. M. Antoun
  • H. K. Cheow
  • R. W. Kirollos
  • J. D. Pickard
  • H. L. Simpson
  • S. J. Jefferies
  • N. G. Burnet
  • M. Gurnell


Pituitary carcinoma occurs in ~0.2% of resected pituitary tumours and carries a poor prognosis (mean survival <4 years), with standard chemotherapy regimens showing limited efficacy. Recent evidence suggests that temozolomide (TMZ), an orally-active alkylating agent used principally in the management of glioblastoma, may also be effective in controlling aggressive/invasive pituitary adenomas/carcinomas. A low level of expression of the DNA-repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) predicts TMZ responsiveness in glioblastomas, and a similar correlation has been observed in the majority of aggressive pituitary adenomas/carcinomas reported to date. Here, we report a case of a silent pituitary corticotroph adenoma, which subsequently re-presented with Cushing’s syndrome due to functioning hepatic metastases. The tumour exhibited low immunohistochemical MGMT expression in both primary (pituitary) and secondary (hepatic) lesions. Initial TMZ therapy (200 mg/m² for 5 days every 28 days—seven cycles) resulted in marked clinical, biochemical [>50% fall in adrenocorticotrophic hormone (ACTH)] and radiological [partial RECIST (response evaluation criteria in solid tumors) response] improvements. The patient then underwent bilateral adrenalectomy. However, despite reintroduction of TMZ therapy (further eight cycles) ACTH levels plateaued and no further radiological regression was observed. We review the existing literature reporting TMZ efficacy in pituitary corticotroph tumours, and highlight the pointers/lessons for treating aggressive pituitary neoplasia that can be drawn from experience of susceptibility and evolving resistance to TMZ therapy in glioblastoma. Possible strategies for mitigating resistance developing during TMZ treatment of pituitary adenomas/carcinomas are also considered.


Temozolomide Pituitary corticotroph adenoma/carcinoma Hepatic metastases MGMT 



This work was funded in part through the UK National Institutes for Health Research (NIHR) Cambridge Biomedical Research Centre (AKA, JDP, NB, MG).

Conflict of interest

The authors have no disclosures to report.


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • A. K. Annamalai
    • 1
  • A. F. Dean
    • 2
  • N. Kandasamy
    • 1
  • K. Kovacs
    • 3
  • H. Burton
    • 1
  • D. J. Halsall
    • 4
  • A. S. Shaw
    • 5
  • N. M. Antoun
    • 5
  • H. K. Cheow
    • 5
  • R. W. Kirollos
    • 6
  • J. D. Pickard
    • 6
  • H. L. Simpson
    • 1
  • S. J. Jefferies
    • 7
  • N. G. Burnet
    • 8
  • M. Gurnell
    • 1
  1. 1.Metabolic Research Laboratories, Institute of Metabolic ScienceUniversity of Cambridge & Addenbrooke’s HospitalCambridgeUK
  2. 2.Department of PathologyAddenbrooke’s HospitalCambridgeUK
  3. 3.Department of PathologySt. Michael’s Hospital, University of TorontoTorontoCanada
  4. 4.Department of Clinical BiochemistryAddenbrooke’s HospitalCambridgeUK
  5. 5.Department of RadiologyAddenbrooke’s HospitalCambridgeUK
  6. 6.Department of NeurosurgeryAddenbrooke’s HospitalCambridgeUK
  7. 7.Department of OncologyAddenbrooke’s HospitalCambridgeUK
  8. 8.Department of OncologyUniversity of Cambridge & Addenbrooke’s HospitalCambridgeUK

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