A Severe Case of Hypothyroidism: Immunotherapy Induced

Background: Immune check point inhibitors are playing a crucial role in the treatment of many cancers. Their primary role is to reactivate anti tumor cytotoxic T cells. Programmed cell death 1(PD 1) is a transmembrane protein expressed on T cells, B cells and Natural killer cells. PD 1 ligand is expressed in many tumor cells along with hematopoietic cells and their interaction directly inhibits apoptosis of the tumor cell. Pembrolizumab binds PD1. FDA approved pembrolizumab initially for nonsquamous cell lung cancer and metastatic melanoma that express PD1 ligand which showed improved survival compared to standard therapy. Additionally it has been used in several others tumors with more than 50% PD L1 expression. Although well tolerated, these agents can cause immune related adverse events. Thyroid dysfunction is reported to range between 3.2-10.1% patients receiving pembrolizumab. Clinical Case: 86 year old Caucasian female with past medical history of hypertension and osteoarthritis was diagnosed with stage III metastatic colon cancer in the hepatic flexure and underwent hemicolectomy. Pathology showed 6.5cm mass and 2/30 lymph nodes positive. Due to fear of side effects from chemotherapy, patient refused further treatment. Her follow up labs showed elevation of carcinoembyronic antigen (CEA). Her oncologist suggested Pembrolizumab, immunotherapy. She was started on 5 cycles every 3 weeks. She had fatigue and fell twice after first cycle, but her CEA levels were improving, so it was decided to continue treatment. Soon after fifth cycle she became extremely weak, lethargic, and unable to do any ADLS and was exhausted all the time. Her labs showed TSH 137, free T4 0.4. At that point decision was made to stop pembrolizumab. She was started on levothyroxine 25mcg by her oncologist and referred to me few months later. She complained of tiredness, low energy. On exam Pulse 78, Blood pressure 152/77. Her labs showed TSH 106 and Free T4 0.45. Her levothyroxine dose was increased to 75mcg and followed her 6 weeks later. Her energy levels improved significantly and she is back to her normal self. Her thyroid function was normal. At this point patient has decided not to undergo any treatments for colon cancer. Conclusion: Immune related thyroid events are increasingly noticed with wide use of pembrolizumab. There is insufficient evidence to suggest the cause of these events. Reversible destructive thyroiditis and overt hypothyroidism are the common clinical presentations. It is important to recognize patients at high risk for these adverse events so these highly efficacious agents can be safely used in patients. Thyroid has been a frequent target for anti PD 1 treatments, further research can be of benefit to use against thyroid cancers.