Clinical characteristics of programmed cell death-1 inhibitor-associated hypophysitis

Abstract

Objective: To explore the clinical features of programmed cell death-1 (PD-1) inhibitor-associated hypophysitis and improve the understanding of the disease. Methods: For the present retrospective case series study, the clinical data of patients with PD-1 inhibitor-associated hypophysitis who were treated at the Affiliated Hospital of Hebei University and the 3rd Hospital of Hebei Medical University from January 2020 to May 2023 were collected for analysis of clinical manifestations and prognosis. Results: Fifteen cases of PD-1 inhibitor-induced hypophysitis were included, with 13 males and 2 females. The mean age of onset was (62.1±7.5) years, and the median time of onset was 6.5 (4.7, 11.6) cycles of PD-1 inhibitor. At diagnosis, 14 patients complained of gastrointestinal symptoms, and 12 patients complained of fatigue. There were 12, 1, 1, 5, and 1 cases of hyponatremia, hypokalemia, hypoglycemia, hypotension, and fever, respectively. Secondary adrenocortical insufficiency occurred in all cases. Moreover, four patients had secondary hypothyroidism, and two patients had secondary hypogonadism. Posterior pituitary hypofunction was not found. Pituitary MRI showed one case each of vacuolar sella turcica, pituitary cystic lesion, pituitary stalk slightly shifted to the left, high metabolism in the sella turcica, and pituitary abnormal signal, while no abnormalities were found in 11 cases. The follow-up time was (47.66±11.93) weeks. At the last follow-up, one patient's serum levels of adrenocorticotropic hormone and cortisol returned to normal. Conclusions: Hypophysitis associated with PD-1 inhibitors occurs later, and gastrointestinal symptoms and fatigue are the most common clinical manifestations. PD-1 inhibitor-associated hypophysitis mainly manifests as adrenocortical hypofunction, and some cases manifest as hypothyroidism and hypogonadism. In addition, patients with PD-1 inhibitor-associated hypophysitis show no obvious imaging changes in the pituitary gland.