Endocrine Abstracts

Context: The immune checkpoint inhibitor (ICI) therapy is frequently used to treat advanced cancers. Autoimmune adverse events have been reported, such as endocrine side effects including frequent thyroid disorders and more rarely hypophysitis. The aim of this study was to describe retrospectively the association thyroiditis-hypophysitis.

Patients and method: From 99 patients with endocrine side effects of the ImmuCare cohort, 18 patients with hypophysitis were included from 2014: eight patients with hypophysitis alone (H group) and ten patients with association thyroiditis-hypophysitis (ATH group). The median age was 59 years, sex ratio M/F was 14/4. Thirteen patients received anti PD1, four patients anti CTLA4 and one patient a combination of both.

Results: Hypophysitis occurred after a median of five courses and 120 days (72 to 323 days). Ten cases were grade ≤2 and eight cases were grade 3. The discovery was clinical in 14 cases (77%). MRI was available in 17 cases and showed pituitary enlargement in two cases (11%). ACTH deficiency was present in 100% of cases and eight patients (44%) had another associated deficiency (4 gonadotropic deficiency, 3 somatotropic deficiency, 3 thyrotropic deficiency). After a median time of 13 months follow-up, ACTH recovery was observed in one case (5%) at 2 months. Thyroiditis occurred after a median of three courses and 42 days (20 to 180 days). All cases were low grade. The thyroid dysfunction was new-onset hypothyroidism for five patients (50%), sub clinical transient hyperthyroidism for one patient (10%) and hyperthyroidism progressing to hypothyroidism for four patients (40%). Antithyroid peroxidase and antithyroglobulin antibodies were positive for three patients. Levothyroxine therapy was introduced and continued after a median time of 20 months follow-up in 70% of cases. Hypophysitis occurred after the primary thyroid dysfunction in 70% of cases, within a median time of 65 days. In two cases the discovery was simultaneous and in one case hypophysitis occurred 80 days before thyroid dysfunction. Hypophysitis occurred earlier in the ATH group (108 vs. 143 days). The use of anti CTLA4 or combination was more frequent in the ATH group (40% vs 12.5%). In addition to the ACTH deficiency, four patients had another deficiency in the ATH group (40%, vs 50% in the H group). The sex ratio, median age and clinical presentation were not different between groups.

Conclusion: In our cohort, hypophysitis was frequently preceded by a primary thyroid dysfunction. Hypophysitis occurred earlier when it was associated with thyroiditis.