Endocrine Abstracts

Introduction: The indications for anti-PD1 agents have expanded considerably in recent years, particularly for the treatment of melanoma, lung cancer and kidney cancer.

Hypophysitis is a rare complication of anti-PD1 agents (< 1%) often with an atypical presentation, characterized by a later onset and a less symptomatic presentation.

Case report: A 60-year-old woman was diagnosed with a clear cell renal carcinoma, treated with left nephrectomy in 2018. Two years later, peritoneal, ovarian and hepatic secondary lesions of the cancer have been identified. Checkpoint inhibitors immunotherapy was initiated using NIVOLUMAB (anti-PD1) and IPILIMUMAB (anti-CTLA4). Pre-therapeutic thyroid and pituitary workup did not reveal any abnormality. Between the 2nd and 3rd cure the patient developed a thyroiditis with initial hyperthyroidism followed by hypothyroidism. Anti-TSH receptor and anti-thyroperoxydase antibodies were negative. Replacement therapy with LEVOTHYROXINE was introduced. IPILIMUMAB was interrupted and NIVILUMAB was majorated by the oncologist. Unfortunately, no systematic monitoring of the pituitary hormone workup was completed between the different treatment cures. During the following months, the patient complained of severe fatigue and nausea with a tendency to lose weight but with otherwise a normal clinical examination. Hormonal assessment confirmed an isolated corticotropic insufficiency with extremely low cortisol level and undetectable ACTH. The rest of the pituitary hormones were in the normal range, with elevated FSH in relation with menopause and normal prolactin. Pituitary MRI showed no abnormalities. HYDROCORTISONE substitutive treatment rapidly resumed all symptoms.

Conclusion: Hypophysitis induced by anti-PD1 seems to be a different nosological entity. Corticotropic insufficiency is often isolated and the symptoms are not very pronounced, apart from fatigue and weight loss which can be attributed to the cancer and/or the treatment regimen used. Through this case, we want to emphasize the importance of hormonal screening before initiating immunotherapy but also regularly during the treatment in order not to miss the diagnosis of a potentially life-threatening pathology.