Abstract
Simple SummaryPrimary adrenal insufficiency (PAI) induced by anticancer drugs is a rare occurrence. However, with the expanding use of immune checkpoint inhibitors (ICIs), an increasing number of patients affected by ICI-induced PAI are expected. As a result, oncologists should be aware of the risk of PAI in patients on ICIs (and other anticancer agents) and the related clinical presentations to diagnose this condition early, provide the appropriate treatment, and timely involve endocrinologists in the management of those patients. In parallel, patients on these medications, together with their caregivers and relatives, should receive detailed information about PAI risk and be trained to act appropriately at the onset of alarm symptoms. Large collaborative trials are needed to develop appropriate tests to assess the personal risk of drug induced PAI better and improve its early diagnosis in cancer patients and patients affected by other forms of PAI.Immune checkpoint inhibitors (ICIs) have improved survival in patients affected by several solid tumours at the cost of new autoimmune adverse events. Endocrine toxicity is frequently reported in patients treated with these agents, mainly as thyroid dysfunction and hypophysitis. Primary adrenal insufficiency is reported in 1–2% of patients receiving a single ICI, but its rate is approximately 5% in patients treated with a combination of two ICIs. The clinical presentation of adrenal insufficiency may be insidious due to symptoms that are not specific. The same symptoms in cancer patients are frequently multifactorial, rendering the early diagnosis of adrenal insufficiency challenging in this group of patients. As adrenal insufficiency can be fatal if not rapidly diagnosed and treated, oncologists should be aware of its clinical presentations to timely involve endocrinologists to offer patients the appropriate management. In parallel, it is essential to educate patients, their caregivers, and relatives, providing them with detailed information about the risk of adrenal insufficiency and how to manage alarming symptoms at their onset. Finally, large collaborative trials are needed to develop appropriate tests to assess better the personal risk of drug-induced adrenal insufficiency and its early diagnosis and treatment, not only in cancer patients.
Highlights
The adrenal gland comprises two distinct anatomical and functional parts: the cortex and the medulla
We focused on Primary adrenal insufficiency (PAI) induced by anticancer drugs
With the expanding use of Immune checkpoint inhibitors (ICIs), an increasing number of patients affected by ICI-induced PAI are expected
Summary
The adrenal gland comprises two distinct anatomical and functional parts: the cortex and the medulla. The cortex produces glucocorticoids (primarily cortisol), mineralocorticoids (primarily aldosterone), and androgens (primarily dehydroepiandrosterone and androstenedione). Adrenal insufficiency (AI) derives from decreased glucocorticoids and/or mineralocorticoids and adrenal androgens production. Primary adrenal insufficiency (PAI), named Addison disease, originates from an injury inherent in the adrenal gland itself. Secondary adrenal insufficiency (SAI) results from damage to the pituitary gland, leading to a decreased secretion of adrenocorticotrophin hormone (ACTH), while tertiary adrenal insufficiency (TAI) arises from a reduced release of corticotrophin-releasing hormone (CRH). Many conditions may trigger PAI (Table 1), including drugs [1,2]. Anti-phospholipid syndrome, anticoagulant therapy, disseminated intravascular coagulation. Congenital adrenal hyperplasia, congenital lipoid adrenal hyperplasia, adrenoleukodystrophy (X- linked), adrenal hypoplasia congenita, autoimmune polyglandular syndrome type 1. Enzyme inhibition (ketoconazole, fluconazole, itraconazole, etomidate, aminoglutethimide, metyrapone, rifampicin, phenytoin, phenobarbital, trilostane, osilodrostat etomidate, suramine, mifepristone, tramadol, abiraterone acetate)
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