Prognostic significance of early ACTH levels on neurological recovery in patients with aneurysmal subarachnoid hemorrhage: a prospective cohort study.

Abstract

Background/objectives: Aneurysmal subarachnoid hemorrhage (aSAH) triggers a marked systemic stress response and may be accompanied by hypothalamic-pituitary-adrenal (HPA) axis dysregulation. Adrenocorticotropic hormone (ACTH) may reflect the acute neuroendocrine response to injury and could be associated with early functional status. This study aimed to describe the frequency of acute-phase ACTH abnormalities and evaluate the association between early ACTH levels and functional outcomes at hospital discharge in patients with aSAH.

Methods: In this prospective cohort study, 20 consecutive aSAH patients admitted within 48 hours of symptom onset were enrolled. Plasma ACTH levels were obtained at random time points within the first 48 hours of admission (predefined cutoff ≤7 days; no patient exceeded 48 hours), prior to definitive aneurysm treatment. Blood samples were obtained within 24 hours of admission and prior to surgical intervention. Sampling was targeted between 08:00 and 10:00 to minimize circadian variation; however, minor deviations were unavoidable in the acute neurocritical care setting. Functional outcomes were assessed at discharge using the Glasgow Outcome Score (GOS) and Modified Rankin Scale (MRS). Associations were evaluated using Spearman correlation, non-parametric group comparisons, and exploratory multivariable regression analyses adjusting for key severity variables.

Results: Using institutional laboratory reference ranges, 12/20 patients (60%) had ACTH values below the reference range, 7/20 (35%) were within range, and 1/20 (5%) had elevated ACTH. ACTH levels were significantly associated with discharge outcomes (mRS: ρ = +0.67, p = 0.0014; GOS: ρ = -0.59, p = 0.0063). ACTH distributions differed between favourable (mRS ≤ 2) and unfavourable (mRS > 2) outcome groups (p = 0.014). In exploratory multivariable analysis, ACTH showed a consistent association with outcome but did not remain statistically significant after adjustment.

Conclusions: Early ACTH levels obtained during the acute hospitalization were associated with short-term functional outcomes at discharge after aSAH. Given the random sampling design, the stress-sensitive nature of ACTH, and the absence of paired cortisol measurements, these findings should be interpreted as reflecting ACTH dysregulation rather than definitive endocrine deficiency. Larger studies with standardized sampling and longer-term follow-up are warranted.