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. 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 conclusively 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 e.g. hypophysitis due to adrenal reserve. ii) When there is mismatch between the clinical and biochemical presentation, the ACTH should be repeated using a different assay.

Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic–pituitary–adrenal axis suppression

“…As part of our work, in a hospital whose oncology service is the Irish national referral centre for several malignancies, we manage ever increasing numbers of immunotherapy-related hypophysitis and would like to share some further observations. The authors state that the Society for Endocrinology and French Endocrine Society guideline recommend performing a short synacthen test (SST) 'if an early morning cortisol is between 138-500 nmol/L, to diagnose "latent" adrenal insufficiency' (Bi et al, 2022). It is important to clarify that the guideline's recommendation refers solely to cases of adrenalitis and not hypophysitis .…”

“…We thank Bi and colleagues for their recent case report ‘Potential pitfalls in diagnosis of immunotherapy-induced hypothalamic–pituitary–adrenal axis abnormalities: a clinical case’ ( Bi et al 2022 ). It provides important lessons on the investigation and management of immunotherapy-related hypophysitis, which is an evolving area within endocrinology and oncology.…”

“…The authors state that the Society for Endocrinology and French Endocrine Society guideline recommend performing a short synacthen test (SST) “if an early morning cortisol is between 138 and 500 nmol/L, to diagnose ‘latent’ adrenal insufficiency” ( Bi et al 2022 ). It is important to clarify that the guideline’s recommendation refers solely to cases of adrenalitis and not hypophysitis ( Castinetti et al 2019 ).…”