Endocrine Abstracts

Pituitary dysfunctions, reported as ‘hypopituitarism’ or ‘hypophysitis’, are relatively common side-effects induced by monoclonal antibodies (mAbs) inhibiting specific immune checkpoints. In particular, 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 (0–17%) and seemed to be dose-dependent. Higher rate of hypophysitis (14%) is associated with the administration of ipilimumab in combination with bevacizumab, while, on the other hand, hypophysitis was not reported in patients treated with ipilimumab and pretreated with chemotherapy or radiotherapy, suggesting that the immune cell depletion induced by cytotoxic chemotherapy and radiotherapy may prevent mAbs induced pituitary dysfunctions. Tremelimumab has been reported to induce hypophysitis in 0–2.5% of patients.

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 (LH). At MRI a pituitary swelling can appear sometimes with thickening of the stalk. As in patients with classic LH, 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.

Moreover, cases of hypopituitarism have been attributed also to interferons (with or without ribavidin) in patients affected by hepatitis C. No cases of pituitary dysfunction were reported with lambrolizumab, a mAb against PD1.

In conclusion, hypophysitis and hypopituitarism represent possible side effects of anticancer drugs. This is a real recent knowledge, because until the advent of anti-CTLA4-mAbs, hypophysitis was never described in association with anticancer drugs. The precise mechanism of injury to the endocrine system triggered by these drugs is still to be fully elucidated but these conditions must be promptly recognized because they may be life-threatening.