title: Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma.
abstract: BACKGROUND
  Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy.
  
  
  OBJECTIVE
  To determine the burden of thyroid dysfunction in patients with melanoma treated with immune checkpoint inhibitors and describe the clinical course.
  
  
  METHODS
  Consecutive patients with melanoma treated with either ipilimumab, nivolumab, pembrolizumab or the combination of ipilimumab and nivolumab were identified. Baseline thyroid function tests were used to exclude those with pre-existing thyroid abnormalities, and thyroid function tests during treatment used to identify those with thyroid dysfunction.
  
  
  RESULTS
  Rates of overt thyroid dysfunction were in keeping with the published phase 3 trials. Hypothyroidism occurred in 13·0% treated with a programmed death receptor-1 (PD-1) inhibitor and 22·2% with a combination of PD-1 inhibitor and ipilimumab. Transient subclinical hyperthyroidism was observed in 13·0% treated with a PD-1 inhibitor, 15·9% following a PD-1 inhibitor, and 22·2% following combination treatment with investigations suggesting a thyroiditic mechanism rather than Graves' disease, and a high frequency of subsequent hypothyroidism. Any thyroid abnormality occurred in 23·0% following ipilimumab, 39·1% following a PD-1 inhibitor and 50% following combination treatment. Abnormal thyroid function was more common in female patients.
  
  
  CONCLUSIONS
  Thyroid dysfunction occurs commonly in patients with melanoma treated with immune checkpoint inhibitors, with rates, including subclinical dysfunction, occurring in up to 50%.
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.|Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
authors.forename: D L
authors.identifier: http://orcid.org/0000-0003-1565-8617
authors.initials: DL
authors.lastname: Morganstein
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.|Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Lai
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Spain
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.|Department of Oncology/Hematology, Cantonal Hospital St. Gallen, Switzerland, Switzerland.|Department of Oncology/Hematology, Hospital Grabs, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Diem
authors.affiliation: Department of Nuclear Medicine, Royal Marsden Hospital, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Levine
authors.affiliation: Department of Endocrinology, Chelsea and Westminster Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Mace
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Gore
authors.affiliation: Skin Unit, Royal Marsden Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Larkin
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D060908:CTLA-4 Antigen / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000150:complications* / Q000188:drug therapy*; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors*; D013959:Thyroid Diseases / Q000139:chemically induced / Q000503:physiopathology*; D013960:Thyroid Function Tests
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D000077594:Nivolumab