Adrenal insufficiency (AI) is one of the immune-related adverse events (irAEs) associated with immune checkpoint inhibitors (ICIs). Although the incidence of ICI-induced AI is low, delayed diagnosis of AI could lead to serious outcomes such as adrenal crisis. Few studies have described the detailed clinical features of this rare, but potentially life-threatening irAE.
We retrospectively reviewed 145 patients (pts) who developed AI during treatment with ICIs from October 2015 to March 2021 at the multicenter. The pts’ clinical characteristics and laboratory and radiologic findings were collected.
The characteristics were as follows: median age, 68 years (range, 30-85); male/female, 104/41; treatment anti-PD-1/anti-PD-L1/anti-PD-1 plus anti-CTLA-4, 109/6/26. The median time of clinical diagnosis was 4.7 months (range, 0.5-34.7), and the median number of ICI administrations before onset was 6 times (range, 1-60).Enlarged pituitary gland on MRI were noted in 11 pts (7.6%). Among these, 8 pts were under treatment with anti-PD-1 plus anti-CTLA-4 and 3 pts were under treatment with anti-PD-1. Symptoms at the onset of AI included anorexia in 84 pts (58%), and fatigue in 78 pts (54%). As laboratory findings, hyponatremia was observed in 59 pts (41%), and eosinophilia was seen in 56 pts (39%). The median serum cortisol and plasma ACTH levels at diagnosis were 1.40 μg/dL (range, 0.05-30.90) and 3.70 pg/mL (range, 0.5-177.0), respectively. Among 138 pts in which both ACTH and cortisol levels were available, 136 pts (99%) had secondary AI, while only 2 pts (1%) had primary AI. Other endocrinopathies seen in these cases included type 1 diabetes mellitus in 5 pts (3.4%), thyroid dysfunction in 30 pts (21%).
In this study, almost all of the ICI-induced AI cases were secondary to ACTH deficiency. Affected patients showed similar symptoms and findings to those of general AI, but those were not always present. In most cases, AI occurred within the 6 months and the diagnosis was made before the onset of overt symptoms by regular measurement of ACTH and cortisol levels. So, it is important that we should measure ACTH and cortisol levels regularly at least during the first 6 months for early detection.
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