SUN-414 Immune Related Adverse Events: Isolated ACTH Deficiency with Nivolumab/Ipilimumab Combination Therapy

Abstract

Introduction Immunotherapies have become revolutionary treatment modalities for several malignancies. These treatments can result in endocrine immune-related adverse events (IRAE) due to decreased downregulation of auto-reactive T cells. The most common IRAE endocrinopathy is thyroiditis, with a lower incidence of pituitary dysfunction observed. Case 77-year-old male with metastatic choroidal melanoma treated with two cycles of Ipilimumab and Nivolumab presented to the hospital with two-week history of generalized weakness, malaise, loss of appetite, and 20 lb weight loss. His concerns were attributed to his known malignancy, however he developed further symptoms of intermittent fevers, hypotension, disorientation, tremors, and garbled speech. MRI brain showed no abnormalities and EEG was normal. The patient gradually developed worsening lethargy, urinary incontinence, spiking fevers, and eosinophilic leukocytosis. Infectious workup revealed a questionable right lower lobe infiltrate on chest x-ray, which was treated with antibiotics. CT chest/abdomen/pelvis showed pulmonary metastases without further abnormalities. With symptoms concerning for adrenal insufficiency, a random cortisol checked resulted at 1.7 ug/dL (normal 3.1 – 22.4 ug/dL). Adrenocorticotropic hormone (ACTH) stimulation test with 250mcg cosyntropin was performed and the highest resultant cortisol level was 9.3 ug/dL (normal 3.1 – 22.4 ug/dL) at 60 minutes diagnosing adrenal insufficiency. Low ACTH level at <5 (normal 7-69 pg/mL) identified secondary adrenal insufficiency. There was no history of exogenous steroid exposure. Further work-up for possible hypophysitis included thyroid stimulating hormone 3.78 ulU/mL (normal 0.36 – 3.74 ulU/mL), free T4 level 1.21 ng/dL (normal 0.76-1.46 ng/dL), prolactin 18 ng/mL (normal 3.5 – 19.4 ng/mL in male), follicle stimulating hormone 26.7 mIU/mL (normal 1.0 -12.0 mIU/mL in male), luteinizing hormone 23.6 mIU/mL (normal 0.6-12.1 mIU/mL in male), and insulin growth factor-1 45 ng/mL (normal 25-240 ng/mL). He was diagnosed with autoimmune secondary adrenal insufficiency secondary to isolated ACTH deficiency from Nivolumab/Ipilimumab combination immunotherapy. Treatment was initiated with methylprednisolone 60mg intravenously every 12 hours and his symptoms improved rapidly. Discussion This case uniquely exhibits immunotherapy induced isolated ACTH deficiency, rather than hypophysitis. Hypophysitis can occur with an adverse event rate up to 17% while on Ipilimumab, however isolated ACTH deficiency is less common. Diagnosis is challenging with symptomatology mimicking common malignancy complaints. It is important for all physicians to be able to recognize symptoms of adrenal insufficiency, especially as a side effect of immunotherapy, as this condition is life threatening without immediate diagnosis and treatment.