Journal of Endocrinological Investigation

, Volume 41, Issue 5, pp 549–556 | Cite as

Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution

  • F. Guaraldi
  • R. La Selva
  • M. T. Samà
  • V. D’Angelo
  • D. Gori
  • P. Fava
  • M. T. Fierro
  • P. Savoia
  • E. Arvat
Original Article

Abstract

Purpose

Autoimmune diseases are typically associated with immune checkpoints blockade. This study aims at assessing, in real-life clinical practice, the prevalence and impact of thyroid disorders induced by immune checkpoint inhibitors.

Methods

52 patients (30 F; age 61 ± 13 years) with advanced melanoma treated with ipilimumab (3 mg/kg i.v./3 weeks; 4 doses) were included. For disease progression, 29 (16 F) of them received nivolumab (3 mg/kg i.v./2 weeks) or pembrolizumab (2 mg/kg i.v./3 weeks). Thyroid function and autoimmunity were assessed before, after 6 weeks, at the end of ipilimumab, as well as before and every 3 months during nivolumab/pembrolizumab treatment.

Results

During ipilimumab, 7 (4 F) patients developed thyroid dysfunction (4 thyroiditis, 1 associated with hypothyroidism; 2 thyrotoxicosis in a previously euthyroid multinodular goiter; 1 hypothyroidism worsened). During PD1 inhibitors, 7 patients (3 F) developed hypothyroidism with severe manifestations in 6 of them; 3 patients suffered from euthyroid autoimmune thyroiditis from baseline, one after ipilimumab; 2 patients developed after transient thyrotoxicosis. Mean follow-up after anti-CTLA4 inhibitors treatment was 36 ± 28 months. Thyroid disorders occurred 45.1 ± 20.8 and 151 ± 67 days after the initiation of CTLA4 and PD1 inhibitors, respectively. Autoimmune disorders and BRAF mutation were associated with a better clinical response to CTLA4 followed by PD1 treatment.

Conclusions

Immune checkpoint blockade is burdened by a high incidence of autoimmune thyroid dysfunction, which is often severe. Therefore, early and careful monitoring and, eventually, treatment are crucial to prevent the negative impact of thyroid dysfunction on the clinical outcome.

Keywords

CTLA4 PD1 Immune checkpoint inhibitors Thyroid diseases Autoimmunity Melanoma 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare 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.

Informed consent

Informed consent was obtained from all individual participants included in the study that was approved by the Hospital Ethics Committee.

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Copyright information

© Italian Society of Endocrinology (SIE) 2017

Authors and Affiliations

  • F. Guaraldi
    • 1
    • 2
  • R. La Selva
    • 3
  • M. T. Samà
    • 1
  • V. D’Angelo
    • 1
  • D. Gori
    • 4
  • P. Fava
    • 2
  • M. T. Fierro
    • 2
  • P. Savoia
    • 5
  • E. Arvat
    • 1
  1. 1.Division of Oncological Endocrinology, Department of Medical SciencesUniversity of TurinTurinItaly
  2. 2.Pituitary Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM), IRCCS Institute of Neurological Sciences of BolognaUniversity of BolognaBolognaItaly
  3. 3.Division of Dermatology, Department of Medical SciencesUniversity of TurinTurinItaly
  4. 4.Hygiene, Public Health and Medical Statistics Unit, Department of Biomedical and Neuromotor Sciences (DIBINEM)University of BolognaBolognaItaly
  5. 5.Department of Health Sciences“A. Avogadro” University of Eastern PiedmontNovaraItaly

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