Immunotherapy-induced autoimmune hypophysitis

Abstract

Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

Keywords

Immunotherapy autoimmune hypophysitis nivolumab ipilimumab adverse events

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References

Naidoo

Page

et al.

Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol 2016; 26: 2375–2391.

Valecha

Vennepureddy

Ibrahim

et al.

Anti-PD-1/PD-L1 antibodies in non-small cell lung cancer: the era of immunotherapy. Expert Rev Anticancer Ther 2016; 17: 47–59.

González-Rodríguez

. Rodríguez-Abreu D (GETICA) SGfCI-B. Immune Checkpoint Inhibitors: review and Management of endocrine adverse events. Oncologist 2016; 21: 804–816.

Dillard

Yedinak

Alumkal

et al.

Anti-CTLA-4 antibody therapy associated autoimmune hypophysitis: serious immune related adverse events across a spectrum of cancer subtypes. Pituitary 2010; 13: 29–38.

Robert

Ribas

Wolchok

et al.

Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial. Lancet 2014; 384: 1109–1117.

Topalian

Sznol

McDermott

et al.

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32: 1020–1030.

Wolchok

Kluger

Callahan

et al.

Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med 2013; 369: 122–133.

Blansfield

Beck

Tran

et al.

Cytotoxic T-lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer. J Immunother 2005; 28: 593–598.

Juszczak

Gupta

Karavitaki

et al.

Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. Eur J Endocrinol 2012; 167: 1–5.

10.

Marlier

Cocquyt

Brochez

et al.

Ipilimumab, not just another anti-cancer therapy: hypophysitis as side effect illustrated by four case-reports. Endocrine 2014; 47: 878–883.

11.

Joshi

Whitelaw

Palomar

et al.

Immune checkpoint inhibitor-related hypophysitis and endocrine dysfunction: clinical review. Clin Endocrinol 2016; 85: 331–339.

12.

Albarel

Gaudy

Castinetti

et al.

Long-term follow-up of ipilimumab-induced hypophysitis, a common adverse event of the anti-CTLA-4 antibody in melanoma. Eur J Endocrinol 2015; 172: 195–204.