# Elevated Adrenocorticotropic Hormone After Adrenalectomy or Adrenal Ablation and Immune Checkpoint Inhibitors: Adrenal Insufficiency Is Not Always the Culprit

## TL;DR

This paper discusses a new diagnostic challenge where elevated ACTH levels in patients who had adrenal surgery or ablation and are on immunotherapy may not indicate adrenal insufficiency.

## Contribution

The study introduces a novel observation of compensatory ACTH elevation without adrenal insufficiency in patients undergoing adrenal procedures and immunotherapy.

## Key findings

- Four patients showed elevated ACTH without symptoms or biochemical signs of adrenal insufficiency.
- This pattern suggests a compensatory ACTH increase rather than adrenal insufficiency in some cases.
- The findings highlight the need for careful monitoring and investigation in such patients.

## Abstract

Adrenal insufficiency is a known complication of both immune checkpoint inhibitors (ICIs) and resection or ablation of the adrenal glands. In the modern era of immunotherapy, more frequent assessment of the adrenal hormonal axis is performed after initiation of ICIs in order to monitor for such complications. The interpretation of these laboratory tests, such as elevated adrenocorticotropic hormone (ACTH), in patients who receive ICIs and undergo adrenalectomy or adrenal ablation provides an additional set of diagnostic challenges that are not well described. We present a case series of four patients who had elevated ACTH without clinical (symptoms) or biochemical (decreased cortisol) evidence of adrenal insufficiency, a pattern suggesting a compensatory increase in ACTH. This highlights an emerging phenomenon and diagnostic challenge in the monitoring of the adrenal axis in patients undergoing adrenalectomy or ablation alongside ICI therapy, emphasizing the need for close follow-up and thorough investigation to rule out adrenal insufficiency in such patients.