Risk assessment, diagnosis, and treatment of cancer treatment-related adrenal insufficiency

ABSTRACT

Introduction

Adrenal insufficiency (AI) is an easily treatable, potentially life-threatening condition, which is increasingly recognized in malignancy. The recent introduction of immune checkpoint inhibitors, in particular, and increasing use of tyrosine kinase inhibitors have increased the frequency of AI in patients with malignancy. A review is therefore warranted to summarize current knowledge on the topic and guide safe clinical practices.

Areas Covered

Malignancy may directly impact the hypothalamic-pituitary-adrenal axis and cause AI, or their treatment including surgery, radiotherapy and medication. In this narrative review, we discuss new causes of AI, recognition of suggestive clinical features, diagnosis and subsequent treatment, aiming to avoid potentially fatal adrenal crisis (AC). Standard literature searching and authors assessment of clinical applicability were used.

Expert Opinion

Adrenal insufficiency can be easily treated once identified but life threatening if unrecognized. While use of new agents such as immune checkpoint inhibitors (ICIs) is increasing, greater understanding of the mechanism of AI is needed to target prediction tools and enhance risk stratification.

KEYWORDS:

• Adrenal insufficiency
• malignancy
• immune checkpoint inhibitor
• adrenal crisis
• hypocortisolism
• cancer
• hypophysitis

Article highlights

• Adrenal insufficiency (AI) is increasingly prevalent in malignancy, largely due to the introduction of immune checkpoint inhibitors (ICI).

• AI risk is determined several interlinking factors including underlying type and extent of disease and cumulative dose of concurrent therapy such as ICIs but difficult to stratify.

• Diagnosis should be suspected with symptoms of fatigue, anorexia, nausea, vomiting, weakness, postural dizziness and weight loss or unexplained hyponatremia.

• Confirmatory tests required include a morning cortisol and cosyntropin (ACTH 1–24) stimulation testing.

• Treatment is lifesaving and requires ongoing glucocorticoid replacement, which should be given at higher doses when under metabolic stress.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The authors have no funding to report.