Guntram Lock

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.

Hepatic encephalopathy is a common problem in cirrhosis. The pathogenesis of this complication of advanced liver disease still remains unclear. Magnetic resonance spectroscopy was used to assess prospectively cerebral metabolism in 51 patients with histologically proven cirrhosis (Child–Pugh classes A, B, and C, 18, 18, and 15, respectively) and 36 healthy volunteers. According to the results of psychometric tests, overt hepatic encephalopathy, subclinical encephalopathy, and no encephalopathy were found in 14, 21, and 16 patients, respectively. Myoinositol/creatine ratios in gray (.36 ± .17) and white (.35 ± .22) matter voxel were reduced significantly ( P &lt; .0001) in cirrhotic patients compared with healthy volunteers (gray matter, .51 ± .11; white matter, .64 ± .16). In addition, patients showed a significant reduction ( P = .024) in white matter choline/creatine ratio (.77 ± .27) compared with controls (.92 ± .25), and glutamine/glutamate level was elevated in cirrhotic patients compared with controls (gray matter, P &lt; .0001; white matter, P = .036). Changes in cerebral myoinositol and glutamine/glutamate levels correlated significantly with the severity of hepatic encephalopathy ( P &lt; .0001). However, these metabolic alterations were also detected in patients without hepatic encephalopathy (normal psychometric test results). N –acetyl aspartate/creatine ratios did not differ between patients and controls. Magnetic resonance imaging detected bright basal ganglia in 37 patients, which correlated significantly with portal–systemic shunting and elevation of glutamine/glutamate, but not with the degree of hepatic encephalopathy. In conclusion, magnetic resonance imaging and spectroscopy showed that alterations of cerebral metabolism are common in patients with cirrhosis, even without evidence of clinical or subclinical hepatic encephalopathy.