Adrenal Insufficiency Related to Anti-Programmed Death-1 Therapy

Anticancer Res. 2017 Aug;37(8):4229-4232. doi: 10.21873/anticanres.11814.

Abstract

Background/aim: Adrenal insufficiency is one of the adverse events (AEs) associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can lead to serious conditions. It is necessary to elucidate detailed clinical features of these AEs.

Patients and methods: Patients treated with anti-PD-1 monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at our hospital from January 2013 to December 2016 were identified. The patients' clinical characteristics and laboratory and radiologic findings were collected.

Results: Adrenal insufficiency occurred in 3% of the patients. All patients were male. At the onset of symptoms, eosinophilia (>500/μl) was observed in four cases. Eosinophilia was observed more than a month before onset of symptoms in three cases. Other pituitary hormones remained relatively stable. Radiological evidence of pituitary inflammation was detected only in one case.

Conclusion: Most anti-PD1-related adrenal insufficiency cases involved an isolated ACTH deficiency. Eosinophilia may be an early indicator before the onset of symptoms.

Keywords: Anti-PD-1; adrenal insufficiency; isolated ACTH deficiency; nivolumab; pembrolizumab.

MeSH terms

  • Adrenal Insufficiency / chemically induced
  • Adrenal Insufficiency / pathology*
  • Adrenocorticotropic Hormone / deficiency
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Carcinoma, Non-Small-Cell Lung / complications
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug-Related Side Effects and Adverse Reactions / pathology*
  • Humans
  • Male
  • Middle Aged
  • Nivolumab
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / genetics*
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Programmed Cell Death 1 Receptor
  • Nivolumab
  • Adrenocorticotropic Hormone
  • pembrolizumab