SECONDARY ADRENAL INSUFFICIENCY AFTER SARS-COV-2 INFECTION IN A PATIENT RECEIVING ANTI-PD-1 IMMUNE CHECKPOINT INHIBITOR NIVOLUMAB: A CASE REPORT

Abstract

Background SARS-COV-2 infection outbreak represented a major burden on the continuum of care of patients receiving active cancer treatment, including immunotherapy. In these patients, infection-related symptoms can mimic treatment-related adverse events, thus generating confounding clinical pictures. We report a case of isolated ACTH de ciency which has become clinically apparent during SARS-CoV-2 infection in a patient who had been receiving for more than nine months adjuvant treatment with anti-PD-1 immune checkpoint inhibitor Nivolumab, for a resected stage III melanoma. Main Body After having received the nineteenth dose of adjuvant treatment with Nivolumab, a 65-year-old woman contracted SARS-Cov-2 infection. Her nasopharyngeal swab turned negative four weeks later, with complete resolution of infection-related symptoms except for severe asthenia, apathy and anorexia, which persisted. Patient was then hospitalized to investigate these unexplained symptoms. Radiological studies excluded cancer recurrence. Patient had a known history of nivolumab-induced hypotiroidism and a history of late-onset insulin-dependent diabetes mellitus. Her blood glucose pre-meal values leaned towards hypoglycemia despite her insulin requirements had been signi cantly reduced in the previous weeks. These elements addressed diagnosis towards an endocrinological issue, and a nivolumab-induced adrenal or pituitary de ciency was suspected. Serum ACTH and cortisol (at 8 a.m. and 3 p.m.) levels, which had resulted within normal limits before the start of nivolumab treatment, were both undetectable. Basal levels of other anterior pituitary hormones (GH with IGF1, prolactin, FSH, LH, TSH) were within the limits, leading to an isolated ACTH de ciency diagnosis. Head-MRI did not reveal signs of hypophysitis. A replacement treatment with hydrocortisone 10 mg per day was then started, with rapid clinical bene t. Conclusion Temporal correlation between endocrinopathy and viral infection made etiology de nition challenging and intriguing. An immune-related adverse event had to be considered in our patients who had a history of autoimmune endocrinopathy and a previous nivolumab-induced endocrinopathy. A pathogenic role and a possible synergism of viral infection can be presumed but cannot be demonstrated.

Keywords

• anti pd-1 immune checkpoint-inhibitors
• isolated acth deficit (iad)
• immune-related adverse event
• sars-cov-2 infection