Isolated adrenocorticotropic hormone deficiency following immune checkpoint inhibitors treatment often occurred in polyglandular endocrinopathies

Abstract

Background: With the increasing application of immune checkpoint inhibitors (ICI) in tumor therapy, the occurrence of isolated adrenocorticotropic hormone deficiency (IAD), as one of its adverse effects, is on the rise. Nevertheless, there are only a few studies regarding IAD induced by ICI. This study aimed at investigating the characteristics of IAD induced by ICI and its relationship with other endocrine adverse events. Methods: A retrospective study was conducted in patients with ICI-induced endocrinopathies in Endocrinology Department from January 2019 to August 2022. Clinical features, laboratory findings and therapy information were collected. All patients underwent 3-6-month follow-up. Results: 28 patients with IAD were enrolled. All of them were treated with anti-PD-1/ PD-L1. The median occurrence time of IAD was 24 weeks after starting ICI treatment.Over half of patients (53.5%) also had primary hypothyroidism or fulminant type 1 diabetes mellitus (FT1DM). Other types of endocrinopathy were not found. The interval between two gland damages was 4-21 weeks or at the same time. In the 28patients, primary hypothyroidism (46.4%) was more common than FT1DM (7.1%). Fatigue and nausea were the chief manifestation. Hyponatremia was also easily to be detected. All patients continued oral cortisol during follow-up. Conclusions: IAD induced by ICI could occur independently, and more often in combination with hypothyroidism or FT1DM. This damage could happen at any stage of ICI treatment. Given that IAD can be life-threatening, it is critical to evaluate pituitary function dynamically in patients undergoing immunotherapy.