TY - JOUR
T1 - Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle
AU - Barnabei, Agnese
AU - Corsello, Andrea
AU - Paragliola, Rosa Maria
AU - Iannantuono, Giovanni Maria
AU - Falzone, Luca
AU - Corsello, Salvatore Maria
AU - Torino, Francesco
PY - 2022
Y1 - 2022
N2 - Immune checkpoint inhibitors (ICI) prolong the survival in an increasing number of patients affected by several malignancies, but at the cost of new toxicities related to their mechanisms of action, autoimmunity. Endocrine toxicity frequently occurs in patients on ICI, but endocrine dysfunctions differ based on the ICI-subclass, as follows: agents targeting the CTLA4-receptor often induce hypophysitis and rarely thyroid dysfunction, which is the opposite for agents targeting the PD-1/PD-L1 axis. Recently, few cases of central diabetes insipidus have been reported as an adverse event induced by both ICI-subclasses, either in the context of anterior hypophysitis or as selective damage to the posterior pituitary or in the context of hypothalamitis. These new occurrences demonstrate, for the first time, that ICI-induced autoimmunity may involve any tract of the hypothalamic–pituitary axis. However, the related pathogenic mechanisms remain to be fully elucidated. Similarly, the data explaining the endocrine system susceptibility to primary and ICI-induced autoimmunity are still scarce. Since ICI clinical indications are expected to expand in the near future, ICI-induced autoimmunity to the hypothalamic–pituitary axis presents as a unique in vivo model that could help to clarify the pathogenic mechanisms underlying both the dysfunction induced by ICI to the hypothalamus–pituitary axis and primary autoimmune diseases affecting the same axis.
AB - Immune checkpoint inhibitors (ICI) prolong the survival in an increasing number of patients affected by several malignancies, but at the cost of new toxicities related to their mechanisms of action, autoimmunity. Endocrine toxicity frequently occurs in patients on ICI, but endocrine dysfunctions differ based on the ICI-subclass, as follows: agents targeting the CTLA4-receptor often induce hypophysitis and rarely thyroid dysfunction, which is the opposite for agents targeting the PD-1/PD-L1 axis. Recently, few cases of central diabetes insipidus have been reported as an adverse event induced by both ICI-subclasses, either in the context of anterior hypophysitis or as selective damage to the posterior pituitary or in the context of hypothalamitis. These new occurrences demonstrate, for the first time, that ICI-induced autoimmunity may involve any tract of the hypothalamic–pituitary axis. However, the related pathogenic mechanisms remain to be fully elucidated. Similarly, the data explaining the endocrine system susceptibility to primary and ICI-induced autoimmunity are still scarce. Since ICI clinical indications are expected to expand in the near future, ICI-induced autoimmunity to the hypothalamic–pituitary axis presents as a unique in vivo model that could help to clarify the pathogenic mechanisms underlying both the dysfunction induced by ICI to the hypothalamus–pituitary axis and primary autoimmune diseases affecting the same axis.
KW - Central diabetes insipidus
KW - Endocrinopathy
KW - Hypophysitis
KW - Hypothalamitis
KW - Immune checkpoint inhibitors
KW - Posterior pituitary
KW - Central diabetes insipidus
KW - Endocrinopathy
KW - Hypophysitis
KW - Hypothalamitis
KW - Immune checkpoint inhibitors
KW - Posterior pituitary
UR - http://hdl.handle.net/10807/197346
U2 - 10.3390/cancers14041057
DO - 10.3390/cancers14041057
M3 - Article
SN - 2072-6694
VL - 14
SP - 1057-N/A
JO - Cancers
JF - Cancers
ER -