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Endocrine

, Volume 58, Issue 3, pp 535–541 | Cite as

Prevalence of hypophysitis in a cohort of patients with metastatic melanoma and prostate cancer treated with ipilimumab

  • Lucia Brilli
  • Riccardo Danielli
  • Cristina Ciuoli
  • Luana Calabrò
  • Anna Maria Di Giacomo
  • Alfonso Cerase
  • Patrizia Paffetti
  • Fausta Sestini
  • Brunetta Porcelli
  • Michele Maio
  • Furio PaciniEmail author
Original Article

Abstract

Objective

Ipilimumab is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4, that has been shown to significantly improve survival in patients with metastatic melanoma. Blocking cytotoxic T-lymphocyte antigen-4 elicits T cell activation, proliferation and anti-tumor response, but can also trigger immune-related adverse events. Among immune-related endocrinopathies, hypophysitis represents the most frequent, with an incidence up to 17% in patients treated with ipilimumab.

Design and methods

We report nine cases of ipilimumab-induced hypophysitis in a cohort of 273 patients treated with ipilimumab between 2006 and 2015, as part of clinical trials or after its marketing. Thyroid function tests were scheduled at screening and during follow up (every 21 days) in all patients. Cortisol, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing hormone, and estradiol (for females) or testosterone (for males), prolactin, growth hormone, insulin-like growth factor 1 were measured only in case of clinical suspicion.

Results

The incidence of hypophysitis was 3.3%. The most frequent pituitary failure was adrenocorticotropic hormone and thyroid stimulating hormone secretion with a complete recovery of thyroid stimulating hormone, but not of adrenocorticotropic hormone during follow up. All patients had negative pituitary antibodies. The main symptoms at diagnosis were fatigue and headache.

Conclusion

Clinicians should be aware about the risk of hypophysitis during treatment with immune check-point inhibitors and the necessity of investigating pituitary function during therapy. Pituitary magnetic resonance imaging does not seem pivotal for a definite diagnosis if not performed at the onset of disease.

Keywords

Hypophysitis Ipilimumab Melanoma CTLA-4 

Notes

Acknowledgements

Michele Maio has received research grants and has taken part to advisory boards by Bristol-Myers-Squibb.

Funding

This research did not receive any specific grant from any funding 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.

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Lucia Brilli
    • 1
  • Riccardo Danielli
    • 2
  • Cristina Ciuoli
    • 1
  • Luana Calabrò
    • 2
  • Anna Maria Di Giacomo
    • 2
  • Alfonso Cerase
    • 3
  • Patrizia Paffetti
    • 1
  • Fausta Sestini
    • 1
  • Brunetta Porcelli
    • 4
  • Michele Maio
    • 2
  • Furio Pacini
    • 1
    Email author
  1. 1.Section of Endocrinology, Department of Medical, Surgical and Neurological sciencesUniversity of SienaSienaItaly
  2. 2.Medical Oncology and Immunotherapy Unit, Department of Oncology, Istituto Toscano TumoriUniversity of SienaSienaItaly
  3. 3.Unit of Neuroimaging and Neurointervention, Department of Neurological and Sensorineural SciencesAzienda Ospedaliera Universitaria SeneseSienaItaly
  4. 4.Department of Medical Biotechnologies, Biochemistry DivisionUniversity of Siena, UOC Laboratorio Patologia Clinica, Azienda Ospedaliera Universitaria SeneseSienaItaly

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