Background: Immune checkpoint inhibitors (ICIs), approved in the UK for the treatment of increasingly numerous malignancies, are commonly associated with endocrine sequelae, some of which may be life threatening. Society for Endocrinology guidelines detail management protocols for acute endocrinopathies, however widely accepted standards for their routine detection are lacking. Hypophysitis, clinically and radiologically silent in many, is seen in up to 15% of patients on ICIs and may result in potentially serious hormonal or mass-related complications. Prolactin is an easily measurable, inexpensive, glucocorticoid-independent anterior pituitary hormone which can be abnormal in early pituitary dysfunction.
Hypothesis: Low prolactin in patients on ICIs may predict incipient hypophysitis.
Methods: Retrospective review of all patients referred to joint endocrinology/oncology ICI clinic between January 2018 and May 2019. Prolactin nadir in patients on ICI therapy with subsequent, unequivocal secondary adrenal insufficiency (n=16) compared against control group of prolactin nadir in patients on ICI therapy without hypophysitis (n=32).
Results: Using a cut off of <115 mu/l, a low prolactin had a 93.75% specificity (95% confidence intervals 79.299.2%) and 50% sensitivity (95% confidence intervals 24.775.3%) for predicting hypophysitis in patients on ICIs. The MannWhitney U test demonstrated that the median prolactin was significantly lower in those patients who went on to develop hypophysitis than their matched controls (P = 0.0027).
Conclusions: A nadir prolactin of <115 mu/l is a highly specific but poorly sensitive marker for emergent hypophysitis. Given its low cost and widespread availability, serial measurements could be easily included in patients oncological surveillance blood tests. Those patients with prolactin levels below our proposed cut off should be identified for more intensive monitoring and investigation, with a high degree of suspicion for early hypophysitis. Such measures could prevent emergency hospital admissions when consequent cortisol deficiency becomes acutely manifest.