Nivolumab induced myxedema crisis

Abstract

BackgroundNivolumab is an anti-programmed cell death (anti-PD-1) monoclonal antibody that is approved by Food and Drug Administration for treatment of metastatic non-small cell lung cancer, metastatic melanoma, relapsed Hodgkin lymphoma and advanced renal cell cancer. We report a rare case of myxedema crisis induced by nivolumab in a patient with metastatic squamous cell carcinoma of lung.Case presentationFifty three-year old woman with metastatic squamous cell carcinoma currently on treatment with nivolumab presented with diffuse facial and tongue swelling, slurred speech, depressed mentation, fatigue and weakness. Initial evaluation revealed severe hypothyroidism with thyroid stimulating hormone of 237 micro Unit/mL (Normal Reference range: 0.27–4.20 micro unit/mL) and undetectable free T4. Patient was diagnosed with nivolumab induced myxedema crisis. She was treated successfully with levothyroxine with complete resolution of her symptoms. Nivolumab was safely restarted once the symptoms of myxedema resolved.ConclusionNivolumab can cause immune-mediated endocrinopathies including thyroiditis, hypophysitis, adrenal insufficiency and type 1 diabetes mellitus. High index of suspicion and periodic measurement of thyroid function tests are recommended in patients receiving nivolumab therapy. Our case also suggests that once the myxedema crisis is treated and symptoms are resolved, nivolumab can be safely re-challenged.

A review of cancer immunotherapy toxicity

“…63 Of the patients with thyrotoxicosis, 80% later developed hypothyroidism. Thyroid storm 64 and myxedema crisis 65 have rarely been reported in patients treated with ICI. The median onset of thyroid dysfunction occurs 4 weeks after starting therapy.…”

Management of endocrine immune-related adverse events of immune checkpoint inhibitors: an updated review

“…Hypothyroidism, in most cases, remains permanent, requiring long-term levothyroxine replacement ( 6 , 33 ). Although the majority of the cases had been classified as grade 1 or 2 irAEs, serious complications of hypothyroidism, for example, myxedema crisis ( 72 ) or myopathy ( 73 ) have been rarely reported. Hypothyroidism-associated myopathy was characterized by severe myalgias, arthralgias, and significant creatine kinase elevation, which could be reversed by levothyroxine replacement therapy.…”

Endocrine dysfunction induced by immune checkpoint inhibitors: Practical recommendations for diagnosis and clinical management

“…These findings are in agreement with other retrospective case series, which found that the majority of endocrine irAEs occur during the first 15 weeks of therapy. 16,23 Although the majority of cases of thyroid abnormalities are low grade, 9 and only rarely require withholding ICI treatment or initiating immunosuppressive therapy, a few cases of thyroid storm 24 or severe hypothyroidism 25,26 after the use of ICIs have been reported. It is important to note that presentation with more severe endocrinopathies may become more frequent in patients treated outside of a clinical trial setting, because older patients and those with cardiac dysfunction, who commonly are underrepresented in clinical trials, 27,28 are at high risk of thyroid disorderrelated cardiovascular events.…”