SUN-412 A Unique Case of Isolated ACTH Deficiency Caused by Pembrolizumab

Abstract

Background: The anti-programmed-death-receptor-1 (PD-1) antibody, pembrolizumab, is one of the key immunomodulators for different types of refractory cancers. It is known to cause a variety of endocrinopathies including hypothyroidism, hyperthyroidism, diabetes mellitus, hypophysitis and primary adrenal insufficiency. However, to our knowledge, there are no reports of isolated ACTH deficiency caused by pembrolizumab. Clinical Case: A 61 yo man with a history of Stage IVA (T3, N3, M1b) poorly differentiated pleomorphic NSCLC presented to hospital with 2 weeks of worsening weakness and lightheadedness. Biopsy results revealed >95% PD-L1 expression and he was started on pembrolizumab 200 mg (4.5 mg/kg) every 3 weeks, along with palliative radiation to the right upper chest. Approximately 1 week after the patient’s 6th dose of pembrolizumab, he became weak and lightheaded and was admitted for further management. BP was 95/58 mmHg and biochemical studies demonstrated hyponatremia with a Na 119 mEq/L and K 4.3 mEq/L. . Due to a high suspicion for adrenal insufficiency, an AM cortisol was checked and was undetectable (<1 mcg/dl). Radiologic images were reviewed and the adrenal glands normal in appearance, ruling out metastatic involvement. Subsequent studies demonstrated an undetectable ACTH but FSH, LH, PRL, TSH, free T4 and IGF-1 were all within normal limits. Aldosterone was also normal (13 ng/dL). A Cortrosyn stimulation test demonstrated a flat response (0 min: cortisol <1 microg/dL ; 60 min: cortisol 1.6 microg/dL), consistent with adrenal atrophy. Adrenal antibodies were absent. The patient was started on hydrocortisone, 10 mg in AM and 5 mg at PM. Sodium improved to 133 mEq/L on discharge and remained at 134 mEq/L on follow up with K of 4.0 mEq/L.. Conclusion: Although multiple endocrinopathies have been observed with pembrolizumab, isolated ACTH deficiency has not been previously reported. As immune checkpoint inhibitors are used widely for the treatment of multiple refractory cancers, one should have a heighted awareness for the development of autoimmune endocrine disorders that may include primary or secondary adrenal insufficiency.