Endocrine Abstracts

Introduction: Immunotherapy has transformed the outcomes of various cancers. Monoclonal antibodies against cytotoxic T lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD1) and its ligand, PDL1 target mainly T cells, unleashing the immune system against tumour cells. Immune checkpoint inhibitor therapy results in a variety of immune related adverse events, including various endocrinopathies. Thyroid disorders, pituitary disorders are relatively more common compared to primary adrenal insufficiency and diabetes mellitus. Immune therapy related primary adrenal insufficiency is rare and can present acutely. Its incidence ranges from 1 to 2 % with monotherapy to 5 to 8 % with combination regimens. Presenting symptoms are usually like secondary adrenal insufficiency or can be completely nonspecific. We present a rare case of primary adrenal insufficiency caused by combination immunotherapy.

Case Presentation: A 72-year-old male with a history of hypertension, Type 2 Diabetes and Atrial fibrillation was treated with combination ipilimumab and nivolumab for metastatic melanoma. Following the second cycle, he developed immune-checkpoint inhibitor (ICPi) induced dermatitis which was treated with high dose glucocorticoids (which were subsequently weaned off) and ICPi treatment was held for 2 months. Following cycle 3, the patient developed acute kidney injury which improved with oral glucocorticoid but there was persistent hyperkalaemia which was disproportionate to the creatinine. The patient’s cortisol was unremarkable [444 nmol/l] and due to the ongoing hyperkalaemia, he was commenced on mycophenolate mofetil. He was also treated with sodium zirconium and sodium bicarbonate for the ongoing hyperkalaemia. As an investigative screen renin 19.5 nmol/l(0.3-2.2), aldosterone <50 pmol/l(0-630), sodium (130 mmol/l) and potassium (7.1 mmol/l) were in keeping with hyper-reninaemic hypoaldosteronism. His urea (10 mmol/l), creatinine (117 umol/l) were disproportionate to the electrolyte imbalance, but he maintained satisfactory random cortisol readings of 314 nmol/l. Treated with fludrocortisone which resulted in normalisation of the potassium. Two months later he had further screening bloods and his cortisol was undetectable. He was referred to endocrinology where hydrocortisone was added to his therapy. His ACTH was markedly raised at a value of 1009 ng/l (0-46) in keeping with ICPi-induced adrenalitis and Adrenal antibodies were negative. In retrospect, it was felt that his mineralocorticoid deficiency preceded the glucocorticoid deficiency by at least 2 months representing an earlier presentation of adrenalitis. Clinicians should be aware of the possibility of ICPi-induced adrenalitis in patients who present with refractory hyperkalaemia and hyponatraemia, even in the setting of a normal cortisol measurement.