Immune check point inhibitors represent newly introduced drugs used in the treatment of cancer. These agents are antibody-based therapies targeting cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). These agents, despite their high selectivity, are characterized by new typical endocrine side-effects in particular on autoimmunity.
The spectrum of endocrine diseases experienced by patients treated with these drugs includes most commonly hypophysitis, more rarely thyroid diseases or abnormalities in thyroid function tests, and occasionally primary adrenal insufficiency.
Hypophysitis represents a distinctive side effect of CTLA4-blocking antibodies and is a new form of autoimmune pituitary disease. In initial trials, the incidence of hypophysitis induced by anti-CTLA4-mAbs (ipilimumab and tremelimumab) varied considerably and seemed to be dose-dependent. Higher rate of hypophysitis has been reported with the administration of ipilimumab in combination with bevacizumab.
Presenting symptoms of mAbs-induced hypophysitis are not specific, including headache, fatigue, weakness, while visual impairment may occur, but less frequently compared with classic lymphocytic hypophysitis. At MRI a pituitary swelling can appear sometimes with thickening of the stalk. As in patients with classic lymphocytic hypophysitis, high-dose glucocorticoids are used to treat anti-CTLA4- hypophysitis, but pituitary hormone deficits may be prolonged or even lifelong, despite the prompt initiation of glucocorticoid therapy.
No cases of pituitary dysfunction were reported with lambrolizumab, a mAb against PD1.
About thyroid function, immune checkpoint inhibitors may induce secondary hypothyroidism resulting from hypophysitis as well as these drugs are responsible for a relatively low incidence of thyroiditis. Hypoadrenalism occurs only in a few cases.
In conclusion, immune check point inhibitors can alter endocrine glands in particular acting on autoimmunity. However, the precise mechanism of injury to the endocrine system triggered by these drugs is yet to be fully elucidated.
Disclosure of Interest None declared