Ipilimumab-Induced Hypophysitis May Not Affect All Pituitary Cell Lines: A Case Report

Abstract

Hypophysitis, a rare autoimmune condition, has now emerged as an adverse effect of ipilimumab (anti-cytotoxic T lymphocyte antigen 4 (CTLA4) mAb) therapy. The occurrence of ipilimumab-induced hypophysitis (IH) in studies has varied from 0% to 17%. This condition, because of secondary adrenal insufficiency, may be life-threatening if not recognized and managed promptly. Here we present a case of hypophysitis in the setting of ipilimumab therapy for malignant melanoma. The patient initially presented to his oncologist with a headache, diplopia, fatigue, nausea, hot flashes, anorexia and decreased libido shortly following the third cycle of ipilimumab. He was found to have pituitary enlargement with heterogeneous enhancement on magnetic resonance imaging (MRI). The initial diagnosis was based on clinical features, MRI findings and laboratory evidence of central hypogonadism and adrenal insufficiency. Other hormone levels were not tested that time and were only tested 5 months later when the patient did not tolerate the discontinuation of glucocorticoids. He continued to require glucocorticoid and testosterone replacement 14 months after the diagnosis. This case demonstrates IH causing anterior hypopituitarism leading to central hypoadrenalism, central hypogonadism, reduced prolactin and possibly central hypothyroidism but preserved somatotroph function. Pituitary antibodies may be a possible method of detection of IH in addition to MRI and hormonal investigations. There is insufficient evidence to support the need for discontinuing ipilimumab or the superiority of initial high dose versus physiologic steroid and hormone replacement in the management of IH. Hypopituitarism due to IH may persist for several months or longer after ipilimumab is discontinued. This underlies the importance of continuous supplementation with all the hormones that are deficient as a consequence of hypopituitarism caused by IH. J Endocrinol Metab. 2015;5(5):299-303 doi: http://dx.doi.org/10.14740/jem287w