Ipilimumab/ Nivolumab Induced Adrenal Insufficiency in a Patient with Metastatic Malignant Melanoma

Presentation Number: SUN 375
Date of Presentation: April 2nd, 2017

Anusha Ramadhas* and Jose S. Subauste
University of Mississippi Medical Center, Jackson, MS



The anti-CTLA-4 (anti-cytotoxic T lymphocyte antigen-4) antibody Ipilimumab and the anti-PD-1 antibodies Nivolumab has improved survival in metastatic melanoma. Augmented immune response by the combination treatment carries a risk of adrenal insufficiency.

Clinical case:

A 64 year old male with metastatic melanoma on Ipilimumab and Nivolumab presented with fever, chills, nausea, vomiting, fatigue, decreased energy, loss of appetite, weight loss of 17 lbs in 5 months. Denied any joint pain or muscle pain or TB or fungal infection in the past. Denied being on steroids in the past, any headache or vision problems or any bleeding disorders or being on any anticoagulants. Admission vitals revealed Hypotension with BP 80/51 with fever of 101F. He was treated for pneumonia with antibiotics but was persistently hypotensive even after IV fluids. Examination significant for very sick looking, thin fragile male but no hyperpigmentation. Labs significant for hyponatremia ( 127mmoL/L, n 135-145 mmoL/L) , normal potassium (3.9 mmol/L, n 3.5-5.1 mmol/L).Baseline morning cortisol (1.1 ug/dL, n am 6.7-22.6ug/dL),ACTH ( 4.2pg/ml, n 7.2-63.3 pg/ml)obtained and meanwhile cosyntropin stimulation test done and cortisol after 30 min and 60 min ( 8.6 ug/dL,14.6 ug/dL ,n>18 ug/dL). Meanwhile stress dose glucocorticoids given (Hydrocortisone 100 mg iv one dose followed by 50 mg iv every 6 hourly).Pituitary panel was done and significant for low testosterone (1.1 ng/mL, n 1.8-7.8 ng/mL) with low normal LH (4.2 mIU/mL, n 1.2-8.6 mIU/mL) and FSH (3.5 mIU/mL, n 1.3-19.3 mIU/mL) suggestive of gonadal axis suppression due to acute stress.TSH was suppressed (TSH-0.01 uIU/mL, n 0.34-5.6 uIU/mL) with normal free T4 (0.92 ng/dL, n 0.61-1.12 ng/dL) and Total T3 (106 ng/dL, n 71-180 ng/dL) suggestive of subclinical thyrotoxicosis related to thyroiditis.MRI pituitary was done which showed 2 mm hypoenhancement in the pituitary suggestive of benign pars intermedia cyst and no abnormal mass or enhancement within the sellar or suprasellar region. He clinically improved with his hypotension and hyponatremia resolved the next day. Fatigue, nausea, vomiting and appetite improved. Hydrocortisone was tapered and patient was discharged on oral hydrocortisone. The lack of hypokalemia and hyperpigmentation and the decreased ACTH level was suggestive of central adrenal insufficiency rather than primary adrenal insufficiency.


CTLA-4 inhibitors Ipilimumab and the PD-1 inhibitors Nivolumab have demonstrated clinical efficacy in the management of metastatic malignant melanoma and so all these medications are used in increasing number of patients. Combination treatment can lead to hypophysitis and adrenal insufficiency and the physician must be able to recognize this because often the symptoms are vague and the diagnosis is missed .Prompt diagnosis and management could prevent morbidity and death.


Nothing to Disclose: AR, JSS