SAT-414 A Single Center Retrospective Analysis and Review of Endocrinopathies from Immune Checkpoint Inhibitors Between 2007 and 2017

Immune checkpoint inhibitors (ICI) specifically target and dysregulate immune tolerance. As a result of this immune activation, immune related adverse events (irAEs) are common. These can include endocrinopathies like immune hypophysitis (IH), primary adrenal insufficiency (PAI), autoimmune thyroid disease, Graves disease and type 1 Diabetes Mellitus (T1DM)[1]. The aim of this retrospective review was to describe the prevalence, timing, and clinical characteristics of ICI-related endocrinopathies at our institution. Methods: A retrospective chart review was conducted for all patients between January 01, 2007 and February 01, 2017 who met predefined clinical, biochemical and imaging criteria for endocrinopathies including IH, T1DM, autoimmune thyroid disease, Graves disease and PAI. Results: Among 690 patients who received ICPI during the study period, 91 unique patients with complete data developed endocrinopathies, for an overall prevalence of 13%. The study included 50 (55%) men and 41 (45%) women with a median age of 64 years (range 20-96 years). Grade 2 endocrinopathies were reported more commonly (n=49, 54%); grade 3/4 events were rare (15%). Among the ICIs, Nivolumab was the most common ICI noted for study patients (n=51, 56%). Autoimmune thyroid disease was the most common irAE in our study (n= 63, 9.1% overall prevalence). We also report 25 cases of IH (3.6%), 2 cases of PAI (0.3%) and 1 case of Graves disease (0.1%). Most patients with autoimmune thyroid disease developed subclinical hypothyroidism (n=26, 3.8%) and overt hyperthyroidism (n=21, 3.0%). We note a high median TSH of 67.3 µIU/mL; range- 20.6-111.0 in overt hypothyroidism compared to subclinical hypothyroidism (14.0 µIU/mL; range- 5.6-100 µIU/mL). Overall, median time to developing any endocrinopathy after initiating ICI was 13.7 weeks; range- 0.7-351.5 weeks. Among the subjects who developed IH, the median TSH was 0.37 µIU/mL (0.01 - 62.39 µIU/mL) with a free T4 of 0.74 ng/dL (0.25-1.86 ng/dL) and the median cortisol was 0.80 µg/dL (0.25-24.5 µg/dL). Amongst the IH group, 17 patients developed isolated secondary adrenal insufficiency and 8 patients developed combination of other hormone deficiencies with secondary AI including 6 with secondary hypothyroidism, 1 patient with hypogonadotropic hypogonadism and 1 with hypothyroidism and hypogonadism in addition to secondary AI. Despite development of irAEs, ICI therapy was continued in 59 pts (65%) who developed an endocrine irAE. Conclusions: In summary, this is one of the largest single institution retrospective studies on ICI related endocrinopathies. The majority of endocrinopathies were low grade, and most patients continued ICI treatment. Reference: Barroso-Sousa, Romualdo. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA, Sept 2017