Endocrine Abstracts

Ipilimumab (an anti-CTLA-4 antibody) treatment has been associated with Immune Related Adverse Events (iRAEs) of the endocrine system. However the frequency of iRAEs in programmed cell death (PD-1) receptor agent use is incompletely characterised, though initial studies report an incidence of 0.5%. We present a case of Pembrolizumab-induced hypophysitis in a 47 yo. male with melanoma. Presenting in 2007 with an initial diagnosis of melanoma, with lymph node recurrence in 2013. He entered adjuvant clinical trial of Vemurafenib versus placebo (patient unblined to placebo arm). In 2015 he presented with oligometastatic M1a disease and received 4 courses of Ipilimumab. During this Ipilimumab treatment he had a sarcoidosis-type reaction and erythema nodosum. Pembrolizumab therapy was introduced due to progression of melanoma. While asymptomatic his TSH fell from 0.988 pre-treatment to 0.1 mIU/ml after third course of therapy with fT4 13.43 pmol/l pre vs 15.33 pmol/l post. MRI pituitary was normal. Synacthen test (post stimulation cortisol 570 nmol/l) was normal with a normal GCT for cortisol + Growth hormone. Thyroid USS and uptake scan were normal, TPO and TRAb negative. TSH recovered over 5 days reaching 2.92 mIU/ml. A diagnosis of Grade 2 hypophysitis was made and patient was discharged well. He re-presented 10 days later with severe headache and TSH was 0.045. He received pulse iv steroids then oral steroids as per protocol for Grade 3 hypophysitis. While he demonstrated deficiencies in thyroid and sex hormones requiring temporary supplementation he ultimately had a full recovery in regard to his pituitary function and steroids were tapered to discontinue in full. At 28 months Cortisol was 247 nmol/l (1 pm), TSH 0.557 mIU/l, FT4 13.8 pmol/l, Testosterone 18.8 nmol/l, FSH 2.41, LH 2.03, Prolactin 127 mIU/l. He subsequently commenced immunotherapy with Vemurafenib and Cobimetanib developing transient inflammatory like arthritis which responded to anti-inflammatory therapy and dose reduction in Venurafenib. While hypothyroidism is noted commonly in patients receiving Pembrolizumab, hypophysitis is rare. The recognition and management of hypopituitarism and particularly potential associated adrenal insufficiency is increasingly important in the endocrine management of oncology patients. Our case exemplifies that hormone replacement may not be required longterm in such patients. This case demonstrates the potential to be hormone replacement free post pembrolizumab indused hypophysititis at long term follow up. As these agents are used increasingly in the future this case report may help to direct endocrine management of iRAEs.