Subtype-specific pattern of white blood cell differential in endogenous hypercortisolism

Abstract

Objective: Endogenous hypercortisolism predisposes to impaired immune function and infections. To date, however, it is unknown whether there is a subtype-specific pattern in white blood cell (WBC) and WBC differential (WBCD) count. Methods: Retrospective monocentric cohort study in patients with overt endogenous Cushing’s syndrome (CS) or adrenal incidentalomas and autonomous cortisol secretion (ACS), with WBC/WBCD analysis at initial diagnosis and after biochemical remission. Cut-offs were obtained by receiver operating characteristics analysis. Results: 253 patients were analyzed (Cushing´s disease (CD); n=88; ectopic CS (ECS), n=31; cortisol-producing adrenal adenomas (CPA), n=40; ACS, n=45; adrenocortical carcinomas (ACC), n=49). Total leukocytes and neutrophils correlated positively with serum cortisol after 1-mg dexamethasone (r=0.314 and r=0.428), while a negative correlation was observed for lymphocytes and eosinophils (r= -0.374 and r= -0.380) (each p<0.0001). Similar observations were made for 24h-urinary free cortisol. CD and ECS differed in numbers of neutrophils and lymphocytes (p<0.0001) and were well differentiated at a cut-off of 6.1 for the neutrophil/lymphocyte ratio (NLR; sensitivity 90.0%, specificity 89.4%, AUC 0.918). For adrenocorticotropic hormone (ACTH)-independent CS, the best diagnostic outcome was obtained for the discrimination of CPA and ACC at a cut-off of 187.9 for the platelet/lymphocyte ratio (sensitivity 59.6%, specificity 80.6%, AUC 0.713). For ECS, CPA, and CD, neutrophils decreased (delta -47.0%, -29.7%, and -26.2%) and lymphocytes increased (+123.2%, +78.1%, and +17.7%) already 3 months after remission. Conclusion. Most immune cells correlate with the degree of hypercortisolism and differ among CS subtypes. WBCD changes are already identified three months after remission from endogenous hypercortisolism.

Inflammation-based scores as predictors of treatment response in advanced adrenocortical carcinoma

“…Patients with advanced cancer usually experience a change in peripheral blood cell composition characterized by an expansion of the myeloid components and a reduction of the lymphoid components (Capone et al, 2018). Previous studies evaluating immune parameters in adrenal tumours reported significantly higher NLR in ACC than in non-malignant cases (Mochizuki et al, 2017;Gaitanidis et al, 2019;Sisman et al, 2020;Detomas et al, 2022). Moreover, studies of preoperative inflammation scores in patients with ACC who underwent resection of the primary tumour demonstrated a prognostic role of both NLR and PLR, although the cut-offs utilized and the results slightly differed between studies (Bagante et al, 2015;de Jong et al, 2021;Solak et al, 2021).…”

“…Further interest in inflammatory parameters in ACC derives from the impact of endogenous hormonal secretion and/or exogenous steroid replacement therapy. Cortisol excess can affect white blood cell count and especially NLR and dNLR, due to its effect in increasing the neutrophils ( Detomas et al 2022 ). We assessed the presence of cortisol hypersecretion at treatment initiation, which was associated with worse survival, yet this was not confirmed at multivariable regression.…”

“…ethnical differences) ( Azab et al 2014 , Dolan et al 2017 ), and there is high heterogeneity in the thresholds used ( Dupré & Malik 2018 ). Since most ACCs are associated with autonomous cortisol secretion and immune cell count correlates with the degree of hypercortisolism ( Detomas et al 2022 ), an inflammation-based score may play an even more relevant role in the prognostic stratification of this aggressive cancer. Previous studies have evaluated the prognostic significance of pre-operative inflammation-based scores in patients with ACC undergoing surgery, showing promising results in predicting the diagnosis of primary adrenal malignancies and clinical outcomes, although in small cohorts ( Bagante et al 2015 , Mochizuki et al 2017 , Gaitanidis et al 2019 , Sisman et al 2020 , de Jong et al 2021 , Solak et al 2021 , Detomas et al 2022 ).…”

“…Since most ACCs are associated with autonomous cortisol secretion and immune cell count correlates with the degree of hypercortisolism ( Detomas et al 2022 ), an inflammation-based score may play an even more relevant role in the prognostic stratification of this aggressive cancer. Previous studies have evaluated the prognostic significance of pre-operative inflammation-based scores in patients with ACC undergoing surgery, showing promising results in predicting the diagnosis of primary adrenal malignancies and clinical outcomes, although in small cohorts ( Bagante et al 2015 , Mochizuki et al 2017 , Gaitanidis et al 2019 , Sisman et al 2020 , de Jong et al 2021 , Solak et al 2021 , Detomas et al 2022 ). Recently, Grisanti et al also showed the role of these biomarkers as predictive factors of response to gemcitabine plus capecitabine chemotherapy, currently regarded as a second-line scheme in progressive ACC ( Grisanti et al 2021 ).…”

The promising role of risk scoring system for Cushing syndrome: Time to reconsider current screening recommendations

“…To reduce unnecessary screening and shorten the time of diagnosis, numerous attempts have been made including clinical scores ( 16 – 18 ), automated face recognition ( 19 – 21 ), radiological or clinical assessments of skin thickness ( 22 , 23 ), the quantification of facial plethora with near-infrared imaging ( 24 ), and, more recently, changes in white blood cell count ( 25 , 26 ). This mini-review focuses on the latest progress in clinical risk scoring system for CS.…”