Abstract
Purpose:
Ipilimumab is besides the BRAF inhibitor vemurafenib the first officially approved
medical treatment for metastatic melanoma, which results in improved survival. Ipilimumab
leads to a release of a CTLA4-mediated inhibition of T-cell immunoreactions. Therefore,
patients may also suffer from immune-related adverse events affecting different organs,
which are typically treated by high-dose corticosteroids. Ipilimumab-induced hypophysitis
(iH) has been reported in up to 17% of melanoma patients in clinical trials.
Methods and Results:
Here we present 5 patients with metastatic melanoma and 2 patients with prostate cancer
who developed hypophysitis after ipilimumab therapy. Patients were treated by high-dose
corticosteroid therapy resulting in the resolution of local inflammation but not of
pituitary deficiencies. Partial or complete hypopituitarism remained in all patients.
Pharmacotherapy with high-dose corticosteroids caused complications in 5 patients,
necessitating hospitalization in 4. 2 of the 3 patients with progressive disease died,
while 3 patients had stable disease and 1 patient showed tumor regression after discontinuation
of ipilimumab.
Conclusion:
In summary, with regard to safety and simplicity of hormonal substitution therapy
we have to scrutinize high-dose corticosteroid therapy, though it only improves inflammation
but not neuro-endocrine function and may cause further morbidity. Regression of the
tumor depends on the ipilimumab-mediated immune events, in which high-dose and long-term
corticosteroid therapy for iH appears to be counter-intuitive. Herein, we discuss
screening and the diagnostic as well as therapeutic management of iH in metastatic
cancer patients from an endocrinologic perspective.
Key words
autoimmunity - hypopituitarism - glucocorticoids
