Endocrine Abstracts

We present a 60-year-old man who was referred to endocrine clinic with fatigue and a random cortisol of 136nmol/l . He had clear renal cell carcinoma and had right radical nephrectomy 7 years ago. Surveillance scans revealed involvement of mediastinal lymph nodes, pancreas and small bowel and he has pancreatic and small bowel resection in four years ago. He had recurrence a year ago and received Ipilimumab and Nivolumab. Biochemistry revealed low fT4 and inappropriately normal TSH, undetectable prolactin but normal gonadal and growth hormone axes. A clinical diagnosis of immune check point inhibitor hypophysitis was made. He was commenced on replacement hydrocortisone followed by Levothyroxine. MRI pituitary was unremarkable. Low basal cortisol, undetectable ACTH and no significant rise after synacthen administration confirmed loss of pituitary adrenal axis. Patient was taught steroid ‘sick day rules’ and doing well two years after initial diagnosis. Immune check point inhibitors are a novel immunotherapy for several cancers. Endocrine adverse effects include hypophysitis, thyroid dysfunction, primary adrenal insufficiency and rarely autoimmune diabetes mellitus. Immune checkpoint inhibitors associated hypophysitis can cause irreversible hypopituitarism, requiring long-term hormone replacement. As in our case, a normal pituitary MRI does not rule out hypophysitis. Pituitary biopsy is gold standard for diagnosis but is not usually required nor is it practical. Also, ACTH/TSH/ADH deficiency is more common in hypophysitis in contrast to neoplastic or structural lesions where GH/LH/FSH deficiency is more common. Clinicians must be mindful of possibility of hypophysitis or primary adrenal insufficiency and have a low threshold of investigations in patients receiving immune check point inhibitors who present with non-specific symptoms.