Objective  To investigate the clinical characteristics of patients with isolated adrenocorticotropic hormone deficiency (IAD) caused by immune checkpoint inhibitors (ICIs) and provide a theoretical basis for the early detection of endocrine immune-related adverse events caused by ICIs.

  Methods  Clinical data reported till July 2022 were obtained from the Wanfang, VIP, CNKI, PubMed, Web of Science, Embase, and Cochrane Library databases, with 54 studies for a total of 70 IAD patients (51 males and 19 females) analyzed. The age of these patients ranged between 34–87 years, with an average age of (64.17±11.33) years. The clinical data of these patients with IAD due to ICIs were statistically analyzed.

  Results  We found that the tumor type most closely associated with IAD is non-small cell lung cancer 35.7% (25/70), followed by malignant melanoma 24.3% (17/70). Furthermore, the ICI most frequently causing IAD was PD-1 inhibitor 87.1% (61/70). The median diagnostic time of PD-1, PD-L1, and PD-1 combined with CTLA-4 inhibitor was 180.0, 364.0, and 87.5 days, respectively. Moreover, the most common abnormal laboratory indicators in IAD patients were hyponatremia and eosinophilia. The clinical symptoms of these patients improved following glucocorticoid replacement therapy.

  Conclusions  In this study, we established that PD-1 combined with CTLA-4 inhibitor is associated with the shortest time of IAD onset. This indicates that the cortisol and adrenocorticotropic hormone levels of patients should be monitored during and after ICI treatment. Notably, for those patients treated with ICIs, particularly males, hyponatremia and eosinophilia occurring can cause IAD, and thus such patients should be closely monitored.