Endocrine Abstracts

Background: Endocrine-related adverse effects of immune check-point inhibitors (ICIs) have been identified in growing number of cancer patients.

Case presentation: A 49-year-old male with laryngeal cancer applied to ouroutpatient clinic with weakness, loss of appetite, weight loss, nausea and vomiting for the last three weeks. He was diagnosed with T3N1M0 laryngeal squamous cell cancer seven months before this admission and was given concurrent cisplatin and radiotherapy, and he had just received 10th cycle of his pembrolizumab (200 mg every 3 weeks) treatment. He was not given glucocorticoids alongside of pembrolizumab. Physical examination was normal except low blood pressure (90/70 mmHg). Laboratory exam revealed normal serum sodium, potassium and plasma glucose levels. Morning serum cortisol (0.47 mcg/dl) and ACTH(10.1 pg/ml) levels were low. TSH, fT4 and fT3 levels were 6.3 uIU/ml, 11.8 pmol/l and 4.7 pmol/L respectively, showing an increase in TSH from pre-treatment level of 1.6 uIU/ml. Thyroid autoantibodies were negative, and thyroid parenchyma was normal on ultrasound, displaying an incidental nodule with benign ultrasonographic characteristics. Other hormonal axes of anterior pituitary were intact. Pituitary MRI revealed enlarged pituitary gland without infundibular thickening, and loss of posterior pituitary bright spot. He had no symptoms or laboratory signs indicative of diabetes insipidus. Accordingly, a diagnosis of hypophysitis with isolated ACTH deficiency (IAD) secondary to pembrolizumab was made. Oral prednisone in a dose of 10 mg/day was started and tapered down to 5 mg/day in three days which improved symptoms dramatically. Levothyroxine was not started since thyroid function tests turned back to normal during follow up. However, the patient was admitted to our hospital one month later due to severe epigastric pain, nausea, vomiting, and elevated serum amylase, lipase and liver function tests. CT displayed oedematous pancreatic enlargement with increased density, without necrosis. Acute cholecystitis and pancreatitis due to bile duct stones were ruled out. The patient was diagnosed with autoimmune pancreatitis and started on 48 mg/day methylprednisolone which improved symptoms and laboratory signs. Pituitary MRI findings were stable 3 and 6 months after the diagnosis of hypophysitis, however local relapse of laryngeal cancer emerged 6 months following the cessation of pembrolizumab.

Conclusions: The risk of IAD has been reported to be higher in patients using ipilimumab or combined ICI therapies, but few cases were defined who were receiving pembrolizumab treatment only. Our patient also had autoimmune pancreatitis, which is reported to occur less than 1% of pembrolizumab treated patients.