Endocrine Abstracts

Introduction

In recent years, we have observed significant progress in cancer treatment associated with the development of immunotherapy. Nivolumab, an anti-PD-1 antibody, blocks the interaction between PD-1 and its ligands and inhibits the signaling pathway by preventing the tumor-derived PD-L1 from blocking T lymphocytes. In patients with metastatic melanoma, it is used either in monotherapy or in combination with other drugs. Immunotherapy is associated with the possibility of immune-related adverse effects (irAE) including endocrinopathies (3–23%). Thyroid disorders are the most common. Hypophysitis, adrenal insufficiency and diabetes are possible complications which require immediate treatment. We report the case of a patient with metastatic melanoma following Nivolumab therapy who developed adrenal insufficiency and primary hypothyroidism.

Case report

63-year-old male with personal history of melanoma metastatic to lymph nodes, liver and spleen has received treatment with nivolumab every 15 days for 5 months. He was referred to our department for fatigue, appetite loss and weight loss of 10 kg in the last 2 months and relative hypotension. Laboratory data revealed elevated thyroid-stimulating hormone and low free thyroxine and positive TPO antibodies; low morning cortisol without correspondence increase of ACTH. Other pituitary hormones were normal. No enlargement of the pituitary gland was apparent by magnetic resonance imaging. The patient was diagnosed with nivolumab induced secondary adrenal insufficiency and primary hypothyroidism. Hormone replacement with levothyroxine (100 mg/day) and oral hydrocortisone (20 mg/day) was started. Nivolumab was discontinued, resulting in amelioration of his symptoms and hydrocortisone was successfully tapered. Nowadays, the patient is on treatment with levothyroxine replacement and has restarted nivolumab every 15 days, metastatic lesions gradually have decreased in size without any additional treatment. During follow-up, the patient presented normal cortisol response to the Short Synacthen Test.

Conclusions

In the management of patients receiving immunotherapy, awareness of the possibility of irAE is crucial. Many of the irAE are linked to the endocrine system. Before anti-PD-1 treatment introduction, an evaluation of the patient for autoimmune diseases should be performed. Thyroid antibodies and type 1 diabetes-related antibodies are considered risk factors and therefore—when detected—organ-specific immune complications should be expected. We suggest routine monitoring of fasting blood-glucose, blood pressure and serum sodium and thyroid function during nivolumab and other cancer immunotherapies. When unexpected fatigue, hypoglycemia, hypotension or hyponatremia appeared, adrenal deficiency should be taken into consideration.