INDICI INFIAMMATORI SISTEMICI: UN UTILE STRUMENTO PER LA DIAGNOSI DIFFERENZIALE DEI TUMORI IPOFISARI

Abstract

Introduzione:Gli indici infiammatori sistemici hanno un ruolo prognostico in numerose neoplasie e sono utili nell’identificare l’ipercortisolismo di eziologia surrenalica. Obiettivo:Valutare la modulazione degli indici infiammatori sistemici nei diversi istotipi di tumori ipofisari (PitNETs). Metodo: Studio multicentrico retrospettivo in pazienti sottoposti a chirurgia per PitNET. Partendo dai parametri emocromocitometrici preoperatori abbiamo calcolato: rapporto neutrofili-linfociti (NLR), piastrine-linfociti (PLR), linfociti-monociti (LMR) e l’indice infiammatorio sistemico (SII, prodotto di piastrine x NLR). Su base istologica, abbiamo suddiviso i pazienti in: PitNETs non funzionanti (NF-PitNET), corticotropinomi (ACTH-PitNET), corticotropinomi silenti (sACTH-PitNET), somatotropinomi (GH-PitNET) e prolattinomi (PRL-PitNET). Risultati:Abbiamo incluso 328 pazienti, 173 maschi (53%); età mediana all’intervento 57 anni. La maggior parte dei tumori erano NF-PitNETs (59%), seguiti da GH-PitNETs (15%), ACTH-PitNETs (14%), PRL-PitNETs (8%) e sACTH-PitNETs (4%). I pazienti con ACTH-PitNETs avevano NLR e SII significativamente più elevati e LMR inferiore rispetto agli altri istotipi (p<0.05, eccetto vs sACTH-PitNETs). Il PLR risultava più elevato nel gruppo ACTH-PitNETs rispetto a NF-PitNETs e GH-PitNETs (p<0.05). I valori di cortisolo libero urinario (CLUxULN) correlavano positivamente con NLR, SII e PLR (p<0.05). All’analisi ROC, l’SII è risultato il parametro più efficace nel discriminare gli ACTH-PitNETs dagli altri istotipi (AUC 0.847, cut-off 538.3; sensibilità 88%, specificità 76% e accuratezza 79%), simile al CLUxULN (AUC 0.787), ma inferiore rispetto alla valutazione del cortisolo plasmatico dopo test di soppressione con desametasone 1mg (AUC 0.932). Conclusione:I PitNETs ACTH-secernenti presentano un’importante modulazione degli indici infiammatori sistemici. L’SII emerge come parametro semplice ed accurato per differenziare gli ACTH-PitNETs dagli altri PitNETs.

Introduction: Systemic inflammatory biomarkers have been shown to have prognostic value in various cancers and to be able to discriminate patients with hypercortisolism among patients with adrenal lesion. Objective: To investigate the modulation of systemic inflammatory indices across different pituitary tumors (PitNET) histotypes. Method: Retrospective, two-centre study, including patients that underwent surgery for PitNETs. Based on pre-operative blood count we calculated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII: platelet x NLR). According to the pathology report patients were stratified as: non-functioning PitNETs: NF-group; ACTH-secreting PitNETs: ACTH-group; silent corticotropinomas: sACTH-group; GH-secreting PitNETs: GH-group; PRL-secreting PitNETs: PRL-group. Results: We included 328 patients, 173 males (53%), median age at surgery 57 years. The majority of tumors were in the NF-group (59%), followed by GH-group (15%), ACTH-group (14%), PRL-group (8%) and sACTH-group (4%). NLR and SII were significantly higher in the ACTH-group compared to others (p<0.001), except sACTH-group. LMR was significantly lower in the ACTH-group compared to the others (p<0.05), except sACTH-group. PLR was significantly higher in the ACTH-group compared to NF-group and GH-group (p<0.001). Urinary free cortisol levels normalized for the upper limit of normality (UFC×ULN) were positively correlated with NLR, SII, and PLR (p<0.05). ROC curve analysis showed that SII was able to discriminate the ACTH-group from all other groups with high accuracy (AUC 0.847; cut-off 538.3, accuracy 79%), comparable to that of UFC×ULN (AUC 0.787), but lower than serum cortisol post-dexamethasone test 1 mg (AUC 0.932). Conclusions: We observed a dysregulation of systemic inflammatory biomarkers in patients with ACTH-PitNETs. SII is a simple-to-use index to identify patients with ACTH-PitNETs.