Adrenal insufficiency (AI) has been reported in cirrhotic patients both during stable clinical phases, and during critical illness. Several aspects of this condition remain unclear, in particular its pathogenesis. Among the proposed mechanisms there are a lack of substrates for adrenal steroidogenesis, an impairment of hypothalamic pituitary axis (HPA), a structural damage and tissue steroid resistance. We first evaluated a lack of substrates as a potential pathogenic mechanism. A total of 81 cirrhotic patients and 30 normal healthy volunteers were enrolled. Lipoprotein levels were evaluated and adrenal function was assessed by LDSST. Our data showed that lipoproteins were reduced in cirrhosis, HDL and Apo-AI were predictive parameters of AI. In a second study we tested the hypothesis of impairment of HPA axis as a pathogenic mechanism of AI in stable cirrhosis. 121 cirrhotic patients were enrolled, adrenal function was assessed by LDSST, in case of AI a prolonged ACTH stimulation was performed by LST. 55% of the AI patients showed a delayed response after prolonged ACTH stimulation suggesting that the mechanism of AI could be related to HPA axis impaiment. Two parallel studies are on going to test the third hypothesis of AI, such as tissue steroid resistance including both stable and ACLF cirrhotic patients.
Ad oggi è ampiamente nota la prevalenza e la rilevanza clinica dell insufficienza surrenalica nel paziente cirrotico, rimangono tuttavia da chiarire i meccanismi patogenetici responsabili dell insorgenza della sindrome. Numerose teorie patogenetiche sono stata avanzate per spiegare l insorgenza dell insufficienza surrenalica nel paziente epatopatico tra le quali la carenza di substrati per la steroidogenesi, la disfunzione dell asse ipotalamo-ipofisi surrene, il danno strutturale della ghiandola e la resistenza tissutale ai glucocorticoidi. Abbiamo condotto un primo studio con lo scopo di indagare la carenza di substrati quale meccanismo patogenetico dell insufficienza surrenalica del cirrotico. Sono stati arruolati 81 pazienti con cirrosi e 30 sani di controllo, tutte le frazioni lipoproteiche sono state misurate e la funzionalità surrenalica (LDSST) è stata valutata in tutti i soggetti epatopatici. I pazienti cirrotici come noto, mostravano più bassi livelli di lipoproteine circolanti, tuttavia i livelli di HDL e Apo-AI risultavano parametri predittori di insufficienza surrenalica nei pazienti cirrotici stabili. In un secondo lavoro abbiamo invece testato l ipotesi del danno dell asse ipotalamo ipofisi surrene (HPA) come meccanismo patogenetico sottostante la disfunzione del surrene. 121 pazienti cirrotici sono stati consecutivamente arruolati e sottoposti dapprima al LDSST per lo studio della funzione del surrene, in caso di alterata risposta i pazienti sono stati sottoposti al LST, ossia ad una stimolazione prolungata con ACTH per valutare la risposta dell asse HPA. Il 55% dei pazienti con alterata risposta al LDSST mostravano una mancata produzione di cortisolo al LST suggerendo la presenza di un alterazione dell HPA in questi pazienti. Con lo scopo di testare la terza ipotesi patogenetica dell insufficienza surrenalica ossia la resistenza tissutale ai glucocorticoidi stiamo ad oggi conducendo due studi in parallelo su popolazione cirrotica stabile e ACLF.
Studio dei meccanismi patogenetici dell'insufficienza surrenalica nella cirrosi epatica / Privitera, Graziella. - (2017 Nov 21).
Studio dei meccanismi patogenetici dell'insufficienza surrenalica nella cirrosi epatica
PRIVITERA, GRAZIELLA
2017-11-21
Abstract
Adrenal insufficiency (AI) has been reported in cirrhotic patients both during stable clinical phases, and during critical illness. Several aspects of this condition remain unclear, in particular its pathogenesis. Among the proposed mechanisms there are a lack of substrates for adrenal steroidogenesis, an impairment of hypothalamic pituitary axis (HPA), a structural damage and tissue steroid resistance. We first evaluated a lack of substrates as a potential pathogenic mechanism. A total of 81 cirrhotic patients and 30 normal healthy volunteers were enrolled. Lipoprotein levels were evaluated and adrenal function was assessed by LDSST. Our data showed that lipoproteins were reduced in cirrhosis, HDL and Apo-AI were predictive parameters of AI. In a second study we tested the hypothesis of impairment of HPA axis as a pathogenic mechanism of AI in stable cirrhosis. 121 cirrhotic patients were enrolled, adrenal function was assessed by LDSST, in case of AI a prolonged ACTH stimulation was performed by LST. 55% of the AI patients showed a delayed response after prolonged ACTH stimulation suggesting that the mechanism of AI could be related to HPA axis impaiment. Two parallel studies are on going to test the third hypothesis of AI, such as tissue steroid resistance including both stable and ACLF cirrhotic patients.File | Dimensione | Formato | |
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