PEMBROLIZUMAB-INDUCED HYPOPHISITIS IN A PATIENT WITH UNDERLYING HYPOTHYROIDISM PRESENTING AS ADRENAL CRISIS

A CASE REPORT

Abstract

INTRODUCTION/BACKGROUND
Pembrolizumab is a checkpoint inhibitor recently used to treat various types of malignancies. It is an analogue of programme-cell-death-1 (PD1) protein analogue involving immune T-cells and has been shown to cause immunerelated adverse events including endocrinopathies. Most reports related to pembrolizumab were on thyroiditis. We report a case of a patient presenting with adrenal crisis due to hypophisitis after after he was started on treatment with pembrolizumab.

CASE
A 73-year-old female with underlying hypothyroidism and hepatitis-B was diagnosed in 2019 with hepatocellular carcinoma stage C (T2N1M0). Post-lobectomy with lymphnode clearance, she was started on pembrolizumab and planned for 28 cycles. She presented to casualty department after the fourth cycle of chemotherapy with vomiting, diarrhoea, abdominal discomfort and reduced oral intake. There was no hypotension or hypoglycaemia but she had hyponatraemia (Na:125 mmol/l) with normokalaemia. She was treated with intravenous fluid and discharged after 2 days. However, she presented 5 days later with hypotension, hypoglycaemia and severe hyponatraemia (Na: 117 mmol/l) and hyperkalaemia (K 5.8 mmol/l). She was diagnosed with an adrenal crisis and treated with intravenous hydrocortisone. Further hormonal workout revealed low serum cortisol (15 nmol/l) and undetectable ACTH due to hypophisitis. She made remarkable recovery and parenteral hydrocortisone was tapered and shifted to tablet.

CONCLUSION
High index of suspicion for hypophysitis and hormonal deficiencies in patients treated with pembrolizumab is vital to prevent delay in diagnosis of endocrine emergencies such as adrenal crisis. Furthermore, patients not previously diagnosed should be screened and periodically followedup to detect hormonal deficiencies from treatment with immune checkpoint inhibitors.