Case Presentation: 70 year old man with hypertension, Type 2 diabetes mellitus, CVA, T3N0M0 metastatic squamous cell cancer of glossitis s/p total laryngectomy and XRT with recurrent metastasis, post-surgical hypothyroidism and hypoparathyroidism who presented with seizure. Patient developed right pharyngeal mass concerning for recurrence of malignancy and was started on once monthly infusion of Nivolumab on 10/3/2018. On 2/27/2019, patient was admitted at another hospital for seizure. Initial studies revealed hyponatremia with sodium of 118 mEq/L. Labs were significant for primary hypothyroidism and central hypoadrenalism. Patient was treated with stress dose steroids while hospitalized but was not discharged on glucocorticoid replacement. Levothyroxine was optimized. Two weeks after the initial episode, the patient another seizure episode which prompted admission to our hospital. Labs were notable for sodium: 127 mEq/L, cortisol <1, ACTH <5 and TSH 54.81. MRI showed no sellar or suprasellar mass. Patient was started on corticosteroids following which sodium improved. Levothyroxine dose was adjusted to maintain a euthyroid state.
Discussion: Nivolumab is an immune checkpoint inhibitor that works by blocking inhibitory signaling through the programmed death receptor-pathway. This results in activation of cytotoxic T cells that act against tumor cells. However, the drug also creates an imbalance in the immune system resulting in immune related-adverse events (IRAEs) that can involve a variety of organs including but not limited to the endocrine system. Hypophysitis and hypothyroidism are two common IRAEs associated with Nivolumab. The time of onset of endocrine IRAEs on PD-1 inhibitors is approximately 1-6 months. In our patient, central adrenal insufficiency with severe metabolic derangement complicated by seizure developed after only 4 months of treatment.
Conclusions: Hospitalists should be aware of these adverse events so that appropriate management can be implemented as soon as possible.