Dysfunction of the Hypothalamic-pituitary-glandular Axes and Relation to Child-Pugh Classification in Male Patients with Alcoholic and Virus-related Cirrhosis

Objective: To investigate anterior pituitary function (adrenal, somatotropic, thyroid and gonadal axes, and prolactin) in relation to the Child-Pugh score in male patients with alcoholic and virus-related liver cirrhosis.

Method: Anterior pituitary function was evaluated in 52 male cirrhotics (26 Child-Pugh class A (CPA), 16 Child-Pugh class B (CPB) and 10 Child-Pugh class C (CPC)) by a combined pituitary stimulation test, and was compared with 50 age-matched controls.

Results: A normal cortisol response to corticotropin-releasing hormone (CRH) stimulation was demonstrated in 57.6% of CPA patients, 31.1% of CPB patients and 20% of CPC patients, while basal levels of adrenocorticotropic hormone (ACTH) and cortisol in cirrhotics were comparable to those in controls. Levels of basal growth hormone (P < 0.001) and stimulated growth hormone (P < 0.01) were significantly higher in cirrhotics compared with controls, while levels of insulin-like growth factor 1 (IGF-1) were significantly lower (P < 0.001). Basal prolactin levels were elevated significantly in CPC patients (P < 0.01), while stimulated prolactin as well as basal and stimulated thyroid-stimulating hormone (TSH) levels were comparable. Basal luteinizing hormone levels were significantly higher in CPA (P < 0.001) and CPB (P < 0.001) patients, and stimulated luteinizing hormone levels were significantly lower in CPC patients than in controls (P < 0.005). Basal and stimulated follicle-stimulating hormone (FSH) levels were comparable in all groups. Child-Pugh score was correlated positively to prolactin and was correlated negatively to IGF-1, stimulated luteinizing hormone and free testosterone.

Conclusions: In cirrhotics, the hypothalamic-pituitary-adrenal and -gonadal axes and prolactin secretion are impaired. Growth hormone response to growth hormone-releasing hormone (GHRH) is accelerated in cirrhotics. Thus, elevated basal and stimulated levels of growth hormone probably reflect compensation for low levels of IGF-1, which are associated with deteriorating liver function. The aetiology of cirrhosis was found to have no influence on the degree of alteration of the hypothalamic-pituitary-glandular axes.