Endocrine Abstracts

Introduction: Pembrolizumab is a programmed death receptor-1(PD-1)-blocking antibody, used in a variety of advanced malignant tumors with promising results, although adverse events are not rare.

Case report: We present the case of an adult female, with negative personal and family history of autoimmune diseases, who developed malignant superficial melanoma of right wrist 6 years ago. She was initially treated with surgical resection (lesion and ipsilateral axillary lymphadenectomy) and high dose interferon treatment and re-operated due to multiple regional right in transit and left axillary lymph node metastases. Melanoma was positive for B-Raf mutation and the patient received Vemurafenib for 3.5 years and then Ipilimumab for four months (lung metastasis). During that period she developed subclinical hypothyroidism, treated with thyroxin. She finally received treatment with Pembrolizumab (multiple mediastinal and right axillary lymph node metastases) with gradual tumor recession within 4 months. She developed acute pancreatitis, without diabetes mellitus, treated conservatively. Two months after full melanoma recession she developed fatigue, anorexia and diplopia for a few days without significant findings in brain MRI. A 5-month period followed with exacerbations and remissions of somnolence, cognitive dysfunction, anorexia, and weight loss and finally developed hypotension and hypoglycemia. After a low morning cortisol (4 μg/dl) measurement, she received full hydrocortisone replacement therapy with complete symptoms remission. Thyroxin dose was increased and vitiligo was developed during that period. There were no significant findings in hypophysis MRI and melanoma restaging showed complete disease remission. Hormonal profile (2nd menstrual cycle day) showed: PRL 12 ng/ml (1.9–25), LH 1.2 mIU/ml (1.1–11.6), FSH 2.6 mIU/ml (0.7–11.1), E2 461 pg/ml (13–166), SHBG 103 nmol/l (18–114), GH 0.93 ng/ml (0.06–5), IGF-1 195 ng/ml (94–252), ACTH 1 pg/ml (7–50) while SST for cortisol was 1, 3 and 3 μg/dl at 0, 30, 60 min respectively.

Conclusion: Pembrolizumab completely controlled metastatic melanoma in our patient through immune stimulation. Hypophysitis with isolated corticotroph cell destruction was developed as an adverse event. If confirmed in other cases Pembrolizumab could be used in treatment of refractory Cushing’s disease.