<p>Managing Ipilimumab-Induced Hypophysitis: Challenges and Current Therapeutic Strategies</p>

Abstract

Over the past years, progress has been made in cancer immunotherapy following the development of immune checkpoint inhibitors (ICI) that have been proved effective in the management of many malignancies. Ipilimumab, a monoclonal antibody against cytotoxic T-lymphocyte antigen-4 (CTLA-4), has been approved for the treatment of advanced melanoma but has been associated with the development of several endocrine immunerelated adverse events (irAEs). Hypophysitis is the most common endocrine irAE related to ipilimumab with a reported incidence ranging from 1.8% to 17%. The mechanism underlying ipilimumab-induced hypophysitis implicates immune, inflammatory and genetic factors, but there are still some points that are not well understood and remain to be elucidated. The diagnosis is based mainly on clinical, biochemical and imaging data. The majority of patients display multiple hormone deficiencies that may recover or persist for a prolonged period of time with corticotroph deficiency usually being permanent. Immune-related hypopituitarism is treated with replacement of deficient hormones while in severe forms of hypophysitis treatment with high-dose glucocorticoids may be required. Proper evaluation and registration of patients in clinical trials and further investigation are needed to precisely clarify the pathophysiology of the ICI-related hypophysitis, define predictive factors and ameliorate the management and outcome of the disease.

Immune checkpoint inhibitors and adrenal insufficiency: a large-sample case series study

“…Three hundred and twenty-five, 728, 616, and 80 articles were retrieved from the PubMed/Medline, Embase, Web of Science and Cochrane Library databases, respectively, and 8 additional articles were identified from the reference lists of the retrieved articles (7)(8)(9)(10)(11)(12)(13)(14). Ultimately, a total of 114 articles (comprising 206 patients with ICI-induced AI) were included in the study (see Figure 1).…”

Case Report: A Variety of Immune-Related Adverse Events Triggered by Immune Checkpoint Inhibitors in a Subject With Malignant Melanoma: Destructive Thyroiditis, Aseptic Meningitis and Isolated ACTH Deficiency

“…A systematic review reported that the incidences of pituitary disorders induced by anti-CTLA-4, anti-PD-1, and the combination of anti-CTLA4/anti-PD-1 antibodies were 3.2%, 0.4%, and 6.4%, respectively ( 3 ). It is also known that ipilimumab causes multiple anterior pituitary hormone disorders due to hypophysitis ( 9 ). In addition, while both nivolumab and ipilimumab can induce isolated ACTH deficiency ( 8 ), nivolumab more often causes isolated ACTH deficiency ( 10 , 11 ).…”

Immunotherapy-Induced Anterior Hypophysitis

“…Characteristic findings seen on the MRI brain are hypo-enhancing lesions in the anterior lobe of the pituitary gland suggesting fibrosis of the gland [ 10 ]. Depending on the severity of the patient's symptoms, the management includes initiation of corticosteroid therapy, hormone replacement therapy to prevent patients from going into adrenal crisis, and sometimes even discontinuation of the offending agent either temporarily or permanently [ 11 ].…”