Oral Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Thyroiditis related to cancer biological therapy: CTLA-4 and PD-1 blockade (#117)

Teresa Lam 1 , Richard Kefford 2 , David Chipps 1
  1. Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, NSW, Australia
  2. Westmead Hospital and Melanoma Institute Australia, University of Sydney, Sydney, NSW, Australia


New immunomodulatory therapies for malignancies such as melanoma have transformed their management with significantly enhanced survival outcomes1. Antibodies against CTLA-4 (ipilimumab) and the programmed death-1 (PD-1) molecule increase the cytotoxic function of T-cells with excellent tumour response rates1,2  However, these therapies may also result in immune-related adverse effects. We describe 4 patients who developed thyroiditis due to CTLA-4 and PD-1 blockade.

Case Series:

Patient 1 had a background of metastatic melanoma and received ipilimumab. Following 3 cycles of ipilimumab, he developed hyperthyroidism which progressed to hypothyroidism 4 weeks later (table 1). Findings on ultrasound were consistent with thyroiditis. Thyroid antibodies were present and levothyroxine replacement was also required.


Three patients received anti-PD-1 therapy with pembrolizumab (formerly MK3475) as part of the KEYNOTE-001 study, 2 of whom had metastatic melanoma and 1 non-small cell lung cancer. Two patients presented with hypothyroidism 9 – 12 months after commencing pembrolizumab (table 1), preceded by subclinical hyperthyroidism 4 months prior to presentation. The third patient received pembrolizumab at a dose of 10mg/kg and presented with hyperthyroidism after 1 cycle, progressing to hypothyroidism after 4 weeks. In all 3 patients, thyroid antibodies were not detected, but ultrasound findings were consistent with thyroiditis. One patient had a thyroid nodule and underwent fine needle aspiration. Cytology demonstrated benign follicular cells with several multinucleated giant cells. Two patients remain on levothyroxine replacement.

Thyroiditis is a known side effect of both CTLA-4 and PD-1 blockade. CTLA-4 gene polymorphisms are associated with autoimmune thyroid diseases3. The exact mechanisms of anti-PD-1 induced thyroiditis remain unclear, but may be due to a switching of the immune system to an effector T-cell response, resulting in macrophage activation by interferon gamma, and cell-mediated thyroid damage4. Monitoring of thyroid function tests are required with use of these therapies.


  1. Hamid, O et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. The New England Journal of Medicine. 2013;369:134-144
  2. McDermott, DF et al. PD-1 as a potential target in cancer therapy. Cancer Medicine. 2013;2(5):662-673
  3. Min, L et al. Thyroid autoimmunity and ophthalmopathy related to melanoma biological therapy. European Journal of Endocrinology. 2011;164:303-307
  4. Tomer, Y et al. Interferon induced thyroiditis. Best practice and research clinical endocrinology and metabolism. 2009;23:703-712