Ipilimumab/nivolumab: Hypophysitis: case report

A 56-year-old woman developed hypophysitis during treatment with ipilimumab and nivolumab for metastatic melanoma.

The woman, who had metastatic melanoma, was receiving treatment with ipilimumab and nivolumab every 3 weeks [initial dose not stated; routes not stated]. In the week after her first treatment, she reported a few mild morning headaches, which improved with paracetamol [acetaminophen]. After receiving three cycles of ipilimumab 3 mg/kg and nivolumab 1 mg/kg and 8 weeks after her first treatment, she reported daily headaches for at least the prior week and a half. She had headaches at various locations, but no eye or temple pain. Her headache decreased with unspecified NSAIDs to 3 on a scale of 1 to 10. She also reported low energy levels and difficulty in reading. Physical examination did not show any gross visual field defects. Laboratory test at 8 weeks after ipilimumab and nivolumab initiation showed a thyroid stimulating hormone (TSH) level of 0.82 mIU/L, which was gradually decreasing compared to 1.41 mIU/L, 5 weeks prior and 1.21 mIU/L, 2 weeks prior. Also, adrenocorticotropic hormone level was 25 pg/mL and cortisol level was 16.8 pg/dL at 8 weeks after therapy initiation. A contrast-enhanced MRI scan of the brain at 8 weeks of therapy initiation revealed an enlarged ovoidshaped pituitary gland and thickening of the infundibulum. Based on the MRI, laboratory and clinical findings, she was diagnosed with immune-related hypophysitis secondary to ipilimumab and nivolumab.

The woman started receiving treatment with steroid therapy including hydrocortisone. At three days after her last cycle of ipilimumab and nivolumab, she was hospitalised due to colitis (aetiology unknown). She was admitted for 3 weeks and received treatment with methylprednisolone [Solu-Medrol] and infliximab for colitis. Then, she was discharged on a highdose of prednisone, which was later tapered to a maintenance dose of hydrocortisone. She completed a total of four cycles of ipilimumab and nivolumab. Her clinical symptoms including headache and fatigue resolved. A follow-up MRI scan showed resolution of the pituitary enlargement. For more than a year after the initiation of therapy, her adrenocorticotropic hormone level was 5 pg/mL and morning cortisol level was 12.9 pg/dL.

Author comment: "Based both on the constellation of imaging, laboratory, and clinical findings and the known association of hypophysitis during immune-checkpoint inhibitor treatment, the diagnosis of immune-related hypophysitis was made in this patient treated with ipilimumab and nivolumab."

Comstock DE, et al. Headache in the Setting of Immunotherapy Treatment for Metastatic Melanoma. JAMA Oncology 3: 703-704, No. 5, May 2017. Available from: URL: http://doi.org/10.1001/jamaoncol.2016.6611 - USA 803383388