Inflammation-based scores in a large cohort of adrenocortical carcinoma and adrenocortical adenoma: role of the hormonal secretion pattern

Abstract

Background: Serum inflammation-based scores can predict clinical outcome in several cancer types, including adrenocortical carcinoma (ACC). It is unclear whether the extent of inflammation-based scores alterations in ACC reflects malignancy, steroid excess, or both.

Methods: We investigated a large retrospective cohort of adrenocortical adenomas (ACA, n = 429) and ACC (n = 61) with available baseline full blood count and hormonal evaluation. We examined the relationship between different inflammation-based scores [neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI)] and both malignancy and steroid secretion patterns.

Results: All inflammation-based scores differed between ACC and ACA: patients with ACC had higher NLR, PLR, SII and lower LMR and PNI levels compared to ACA (all p values < 0.001). NLR showed a positive correlation with cortisol levels after overnight 1 mg-dexamethasone suppression test (1 mg-DST), both in ACC and ACA (p < 0.01). The ROC curve analysis determined NLR > 2.6 as the best cut-off to discriminate ACC from ACA [AUC = 0.846, p < 0.01]. At multivariable analysis, NLR > 2.6 was independently associated with ACC, 1 mg-DST cortisol levels and age, but not with tumour size. Considering the ACC, NLR and SII were higher and PNI was lower in patients with cortisol excess compared to those without cortisol excess (p = 0.002, p = 0.007, and p = 0.044 respectively). Finally, LMR and NLR differed between inactive-ACC (n = 10) and inactive-ACA (n = 215) (p = 0.040 and p = 0.031, respectively).

Conclusion: Inflammation-based scores are related to steroid secretion both in ACC and ACA. ACCs present a higher grade of inflammation regardless of their hormonal secretion, likely as a feature of malignancy itself.

Keywords: Adrenal cancer; Adrenocortical tumors; Cushing’s syndrome; Inflammation scores; Neutrophil–lymphocyte-ratio.

Fig. 1

A Correlation between cortisol levels after 1-mg overnight dexamethasone-suppression test and neutrophil/lymphocyte ratio (NLR). p-values were determined with Spearman’s correlation coefficient. Gray dots represent patients with adrenocortical carcinoma (ACC, n = 61), black dots represent patient with adrenocortical adenoma (ACA, n = 429). B Area under the curve (AUC) of the neutrophil/lymphocyte ratio (NLR) for distinguishing adrenocortical adenomas (ACA) from adrenocortical carcinomas (ACC)

Fig. 2

Neutrophil/lymphocyte ratio (NLR) in patients with adrenocortical adenomas (ACA) and adrenocortical carcinomas (ACC). 1-mg DST = 1-mg overnight dexamethasone-suppression test. Data are shown as median and interquartile range, the upper and the lower whiskers represent respectively the 90 and the 10 percentiles

Fig. 3

Neutrophil-to-lymphocyte ratio (NLR, A and lymphocyte-to-monocyte ratio (LMR, B for distinguishing inactive adrenocortical adenomas (ACA) from inactive adrenocortical carcinomas (ACC)