Association of ipilimumab therapy for advanced melanoma with secondary adrenal insufficiency: a case series

To present a case series of ipilimumab-related secondary adrenal insufficiency.

In this cases series, we review the presentation, evaluation, diagnosis, and management of patients with advanced melanoma who received ipilimumab and were referred to our endocrinology clinic for evaluation of hormonal abnormalities.

Seven patients presented with symptoms, signs, or biochemical evidence of adrenal insufficiency 6 to 12 weeks after starting ipilimumab therapy. Ipilimumab is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody that is approved for the treatment of metastatic melanoma and has widespread use for this disease. All 7 patients had biochemical evidence of profound secondary adrenal insufficiency. Thyroid function abnormalities, central hypogonadism, and low insulinlike growth factor 1 levels were seen in a subset of patients. Only 2 patients had abnormal findings on pituitary magnetic resonance imaging. Posterior pituitary function remained normal.

Our findings suggest that the enhanced immune response associated with ipilimumab therapy may have a predilection for corticotroph and possibly thyrotroph cells. We recommend periodic hypothalamic-pituitary-adrenal axis monitoring for patients on this therapy.