Immune Checkpoint Inhibitors Pose ACTH Deficiency Risk

Miriam E. Tucker

March 20, 2023

Researchers published the study covered in this summary on Research Square as a preprint that has not yet been peer reviewed.

Key Takeaways

  • Immune checkpoint inhibitor (ICI)–induced isolated adrenocorticotropic hormone deficiency (IAD) can occur independently or in combination with other endocrinopathies such as hypothyroidism and type 1 diabetes, based on a single-center review of 28 cases.

  • No biomarkers are proven to reliably predict incident IAD.

  • All patients receiving ICI treatment need dynamic monitoring of cortisol and adrenocorticotropic hormone (ACTH), with monitoring that continues long term after treatment ends.

Why This Matters

  • ICIs are powerful anti-tumor treatments that can cause unpredictable immune-related adverse events including endocrinopathies.

  • The incidence of IAD has been growing because of increasing ICI use.

  • Some endocrine damage, such as ACTH deficiency, can be fatal and recovery is often impossible.

  • It may be difficult to recognize IAD as its symptoms overlap those of cancer therapy — such as fatigue, and appetite and weight loss — and hence incident IAD may be overlooked when pituitary hormones aren’t routinely measured.

  • This is the first study to provide a comprehensive overview of IAD in patients receiving ICI treatment.

Study Design

  • The study was a retrospective review of 28 patients with ICI-induced IAD seen in the endocrinology department of Zhongshan Hospital of Fudan University in Shanghai, China from January 2019 to August 2022.

Key Results

  • Of the 28 patients diagnosed with IAD, 13 had IAD alone, 13 had IAD plus hypothyroidism, and two had IAD and type 1 diabetes.

  • All but one of these patients had received an anti-programmed cell death receptor-1 (PD-1) or anti-PD-ligand1 (PD-L1). The single exception received a bispecific antibody, AK104, that targets both PD-1 and CTLA4.

  • The median time to develop IAD was 24 weeks into ICI therapy, and the earliest was 4 weeks (after 2 cycles).

  • Fatigue occurred in in all affected patients, nausea occurred in 20 (71%), and hyponatremia occurred in 19 (68%).

  • All patients continued an oral hydrocortisone regimen for 3-6 months.

  • One patient died of tumor metastasis, while the rest continued to receive other treatments.


  • This was a retrospective, observational study with a relatively small sample size.

  • The study only included patients admitted to the endocrinology department, which skewed the study cohort toward a more severely affected population.

  • The study had a short follow-up, which prevented assessment of immune-related adverse effects and treatment effects.

  • Several of the ICIs that the patients received are unavailable outside China, limiting generalizability.


  • The study received no commercial funding.

  • The authors report no relevant financial relationships.

This is a summary of a preprint research study "Isolated adrenocorticotropic hormone deficiency following immune checkpoint inhibitors treatment often occurred in polyglandular endocrinopathies," by researchers from Fudan University, Shanghai, China. The study has not yet been peer-reviewed. The full text of the study can be found on


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