Evidence map›Paper›PMID 40874801›Full record

Observational studyClinical endocrinology2026

Adrenal Insufficiency During Treatment With Immune-Checkpoint Inhibitors: How to Simplify the Diagnostic Pathway?

Alice Nervo, Giovanni Gruosso, Marta Marino, Enrica Migliore, Matteo Rubiolo, Elisa Vaccaro, Emanuela Arvat

Abstract readObservational Study
In one paragraph

Observational study in Clinical endocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Alice NervoOncological Endocrinology Unit, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy.ORCID 0000-0002-9227-2075
Giovanni GruossoOncological Endocrinology Unit, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy.ORCID 0009-0005-5014-8219
Marta MarinoDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
Enrica MiglioreCancer Epidemiology Unit, University of Turin, Turin, Italy.
Matteo RubioloOncological Endocrinology Unit, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy.
Elisa VaccaroOncological Endocrinology Unit, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy.
Emanuela ArvatOncological Endocrinology Unit, AOU Città della Salute e della Scienza, University of Turin, Turin, Italy.

Funding

The authors received no specific funding for this work.
6 · The paper itself

Abstract

OBJECTIVE AND

backgroundEarly identification of adrenal insufficiency (AI) during immune-checkpoint inhibitors (ICIs) is crucial to prevent life-threatening consequences; however, the diagnosis is challenging. DESIGN, PATIENTS AND MEASUREMENT: In this prospective observational study, ICI-treated cancer patients with morning serum cortisol (SC) within the grey zone (83-414 nmol/L) were enroled. A low-dose adrenocorticotropic hormone (ACTH) stimulation test was performed to assess peak stimulated SC, preceded by re-evaluation of morning SC. The analysis aimed to refine morning SC cut-offs to minimize the diagnostic grey zone reducing the need for ACTH stimulation. To interpret the results of ACTH test, it was employed both the threshold for peak stimulated SC provided by the Endocrine Society guidelines (500 nmol/L) and an assay-specific cut-off for the Abbott platform recently proposed in literature (414 nmol/L). Moreover, the utility of salivary cortisol and cortisone upon awakening was explored.

resultsIn 30 ICI-treated patients, a good positive correlation between morning and peak stimulated SC was confirmed (r = 0.72, p < 0.001); peak stimulated SC ≤ 500 nmol/L and ≤ 414 nmol/L was detected in 36.7% and 20% of subjects, respectively; all cases were secondary AI. ROC curve analysis identified optimal morning SC thresholds for AI prediction and exclusion (> 196 nmol/L and ≤ 397 nmol/L in case of pathological peak stimulated SC ≤ 500 nmol/L; > 163 nmol/L and ≤ 251 nmol/L in case of pathological peak stimulated SC ≤ 414 nmol/L). Salivary cortisol and cortisone upon awakening positively correlated with peak stimulated SC (r = 0.49 and r = 0.56, respectively, p < 0.01).

conclusionsMorning SC is a reliable tool for the screening of ICI-related AI; the need for dynamic stimulation would be reduced by the application of assay-specific cut-offs. Salivary hormone analysis of cortisol and cortisone upon awakening may represent a viable alternative in selected cases.

Indexed as

Adrenal InsufficiencyImmune Checkpoint InhibitorsAdrenocorticotropic HormoneAdultAgedCortisoneFemaleHumansHydrocortisoneMaleMiddle AgedNeoplasmsProspective StudiesSalivaAdrenocorticotropic HormoneCortisoneHydrocortisoneImmune Checkpoint Inhibitorshypothalamic–pituitary–adrenal axisimmunotherapyisolated ACTH deficiencysalivary cortisolsalivary cortisoneserum cortisol

Identifiers

PMID40874801
PMCPMC12669809

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.