Endocrine Abstracts

Context: Ipilimumab is a human monoclonal antibody against cytotoxic T lymphocyte antigen-4 (CTLA-4), which enhances stimulation of cytotoxic T lymphocytes, resulting in an immune response against the tumour. This drug-induced hyperactivity of the immune system can lead to serious adverse effects including endocrine disorders such as autoimmune hypophysitis, thyroiditis and adrenal insufficiency.

Objective: To report our experience on ipilimumab-induced hypophysitis (IIH) in patients with advanced cancer.

Results: Four patients (three men (75%); aged 67.5±8.7 years (range, 59–75)) with advanced cancer (three melanomas and one prostate cancer) were recruited. The clinical presentation of IIH was similar in all cases regardless of the underlying tumor. IHH developed after 12–19 weeks of starting treatment, usually between two and four ipilimumab cycles. Main symptoms were fatigue (n=3) and headache (n=2), nausea (n=2) and vomiting (n=2). IIH was associated with partial or total hypopituitarism in three cases. Pituitary hormone deficiencies most frequently affected were corticotrophin (ACTH, n=3), thyrotropin (TSH, n=3) and gonadotropins (FSH and LH, n=3). Two patients showed prolactin and growth hormone deficiencies. One patient did not develop any pituitary hormone deficiency although magnetic resonance imaging (MRI) of the pituitary showed morphologic changes of hypophysitis. MRI study showed enlarged pituitary in three patients. All patients were treated with high steroid doses (>0,5 mg/kg per day of prednisone or equivalent). After 28 months (range, 22.2–35.4) of follow-up, three patients remained with steroid hormone replacement therapy and two patients with replacement doses of levothyroxine. One patient recovered thyroid function.

Conclusion: IIH is an immune-related adverse event that can compromise the patient’s life because of the possibility of development of adrenal and thyroid insufficiency in a high percentage of patients. Glucocorticoids are the treatment of choice. Hormone replacement therapy is indicated according to hormone deficiencies. Patients receiving immunomodulatory therapies should be closely monitored by baseline and follow-up hormone assessment.