Abstract
Introduction Pembrolizumab, a humanized anti-programmed death -1 antibody has been used in the treatment of several malignancies with improved prognosis, but it has been associated with several immune related adverse effects, particularly endocrinopathy. We report a case of pembrolizumab induced isolated ACTH deficiency and resultant adrenal insufficiency in a 77-year-old woman who received immunotherapy for adenocarcinoma of the lung. Case report A 77-year-old woman presented to the hospital with fatigue and worsening shortness of breath. She had a history of stage IV non-small cell carcinoma lung for which she received pembrolizumab for a year, last dose 1 month prior to admission. She denied any long-term exposure to steroids except for a steroid cream which she used for 2 or 3 weeks several weeks before presentation. Her blood pressure was 130/70, pulse 80/min, rest of the physical examination was unremarkable. Labs were significant for Na 127mmol/L, K 4.2 mmol/L, blood glucose of 89 mg/dL, cortisol <0.5 µgm/dL. Cosyntropin stimulation test was performed. After 250 mcg of cosyntropin, her cortisol went to 4.2 µgm/dL and 5.4 µgm/dL at 30 and 60 minutes respectively and ACTH was <5 pg/mL. Aldosterone went from 1 ng/dL to 2 ng/dL but renin was low at 0.14 ng/mL. TSH 0.681 µIU/mL, FT4 1.54 ng/dL, FSH 68.8 mIU/mL and LH 37.5 mIU/mL. Adrenal insufficiency was presumed to be secondary in nature, given the undetectable ACTH and lack of clinical features consistent with primary adrenal insufficiency such as electrolyte imbalance and hypotension and low renin activity. However, her other pituitary hormones like FSH and LH were normal suggesting isolated ACTH deficiency. Pituitary MRI did not show any evidence of hypophysitis and CT abdomen revealed small adrenal glands possibly secondary to atrophy due to prolonged ACTH deficiency. She was started on stress dose steroids initially which was switched on 20 mg hydrocortisone in the am and 10 mg mid-day following clinical improvement. She is doing well on follow up. Conclusion This case highlights a unique presentation of isolated ACTH deficiency in a patient with non-small cell carcinoma lung treated with Pembrolizumab. Advances in immuno-oncology have led to the development of newer immune response modifying agents and many of these are commonly associated with IRAEs. Clinicians should be aware that isolated ACTH-mediated adrenal insufficiency could be the first or only manifestation of hypophysitis or pituitary disease in pembrolizumab treated patients. Therefore, it is important to consider isolated ACTH deficiency as a potentially severe immune-related adverse event of Pembrolizumab, even when MRI pituitary does not show any abnormality.