Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic–pituitary–adrenal axis abnormalities: a clinical case

Abstract

Short synacthen tests (SST) are frequently used for assessing adrenocorticotropin hormone (ACTH) deficiency. In this study, we present the case of a 53-year-old man receiving immunotherapy for metastatic melanoma, who subsequently developed immune checkpoint inhibitor (ICI)-induced hypothyroidism and was investigated for the presence of ICI-induced hypocortisolaemia on different occasions. Despite two reassuring SSTs, he subsequently developed clinical and biochemical evidence of ACTH deficiency. The ACTH on local measurement was not conclusive in keeping with ICI-related ACTH deficiency but when repeated using an alternative assay confirmed the diagnosis. The case illustrates the evolution of ACTH deficiency and exposes the potential pitfalls of screening strategies. Two important lessons may be gleaned from this case: (i) SSTs can be normal in early cases of secondary adrenal insufficiency, for example, hypophysitis due to adrenal reserve and (ii) when there is mismatch between the clinical and biochemical presentation, the ACTH should be repeated using a different assay.

Keywords

• short synacthen test
• sst
• hypophysitis
• immunotherapy
• acth deficiency
• cortisol
• immune checkpoint inhibitor
• assay