Diagnostic Challenge of Immune Checkpoint Inhibitor-Induced Hypophysitis in Patient With Melanoma

Immune checkpoint inhibitors (ICIs) have emerged as immunotherapy treatment modalities for several advanced malignancies. Although effective in cancer treatment, inhibition of cellular checkpoints can result in the loss of immunologic tolerance with consequent autoimmune disorders. Clinicians must be aware of immune-related adverse events (irAEs), such as hypophysitis, to ensure prompt treatment.

A 73-year-old male with a history of metastatic melanoma who had received 5 cycles of pembrolizumab (anti-PD-1) and 2 cycles of combination ICI therapy with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) presented to a US Department of Veterans Affairs medical center 3 weeks after completing his second cycle of therapy with fatigue, headache, and hyponatremia. Laboratory evaluation revealed a low thyroid hormone level with suppressed thyrotropin, consistent with central hypothyroidism. Magnetic resonance imaging of the brain demonstrated pituitary enlargement suggestive of hypophysitis. The patient was treated with intravenous hydrocortisone for suspected central adrenal insufficiency. A subsequent cosyntropin stimulation test confirmed secondary adrenal insufficiency with low adrenocorticotropic hormone levels and a blunted cortisol response. Computed tomography and positron emission tomography showed normal adrenal glands without metastases. The patient's symptoms improved with glucocorticoid replacement, though he later experienced complications of steroid therapy.

Patients presenting with evidence of new autoimmune disorders who have undergone ICI therapy should be immediately evaluated for irAEs. ICI-induced hypophysitis is irreversible, can impact quality of life, and requires maintenance replacement therapy. As ICI therapies become more prevalent in the treatment of solid cancers, it is expected that clinicians will see more cases of ICI-related irAEs, such as hypophysitis, and must become comfortable with diagnosis, treatment, and management.