A study of the endocrine manifestations of hepatic cirrhosis

Abstract

The clinical features and hormonal abnormalities were surveyed in 117 men with cirrhosis of the liver. Compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates, plasma production rates and total and free levels of testosterone, reduced testosterone responses to human chorionic gonadotrophin stimulation, higher oestradiol, luteinizing hormone and follicle stimulating hormone levels and higher binding capacities of sex steroid binding globulin. The peripheral conversion of testosterone to oestradiol was also found to be significantly increased. However, the metabolic clearance and plasma production rates of oestradiol were not significantly different from those of healthy men. Patients who were severely ill with liver failure and one with haemochromatosis had low levels of luteinizing hormone and follicle stimulating hormone and sub-normal responses to clomiphene and luteinizing hormone-releasing hormone. Higher plasma oestradiol levels were found in patients with gynaecomastia and spider naevi than in those without these signs. However, the clinical features of androgen deficiency--that is, testicular atrophy, impotence and loss of secondary sex hair--were only poorly related to the low testosterone levels, and production rates and longtitudinal studies indicated that the hormonal levels, endocrine features and severity of the liver disease could change independently. It is concluded that the clearance of oestradiol from plasma is not limited by liver disease in all patients, and that reduced degradation of oestrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. While gonadotrophin deficiency occurs with liver failure and in some patients with haemochromatosis, the more usual findings are of elevated gonadotrophin levels and a poor Leydig cell response to chorionic gonadotrophin. These suggest that the hypogonadism is primary in most patients with cirrhosis. The causes of the high oestradiol levels were not discovered. Increased peripheral conversion of precursors to oestradiol or increased testicular secretion of oestradiol are possibilities. The high binding capacities of sex steroid binding globulin were not significantly correlated with either the low testosterone or high oestradiol level and the cause of this abnormality remains uncertain. The low metabolic clearance rates of testosterone appeared to result from the increased plasma protein binding of testosterone. The discrepancies in the expected relationships between the hormone and clinical changes suggest that factors other than those studied are also involved in the genesis of the endocrine features of hepatic cirrhosis.

PIP: Blood levels of estradiol, testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex steroid binding globulin (SSBG), and free steroids were surveyed in 117 men to define the pattern of hormonal abnormalities and to examine the relationships between the hormone levels and the development of the endocrine features of cirrhosis. When compared with healthy men of similar ages, the patients had significantly lower metabolic clearance rates (p .001), testosterone production rates (p .001), total and free levels of testosterone (p .001), reduced testosterone responses to human chorionic gonadotropin (HCG) stimulation, higher estradiol, LH, and FSH levels, and higher binding capacities of SSBG. The metabolic clearance and plasma production rates of estradiol were not markedly different from those of controls. Severely ill patients with liver failure of hemochromatosis had low levels of LH and FSH respones to clomiphene and LH-releasing hormone. Patients with gynecomastia and spider naevi had higher estradiol levels than in those without these signs. Longitudinal studies indicated that the hormonal levels, endocrine features, and severity of the liver disease could change independently. It is concluded that the clearance of estradiol from plasma is normal in most patients with liver disease and that reduced degradation of estrogens is not the initial event in the sequence leading to the hormonal abnormalities of cirrhosis. Usual findings of liver failure are elevated gonadotropin levels and a poor Leydig cell response to HCG which suggest that the hypogonadism is primary in most patients with cirrhosis. Discrepancies in the expected relationships between the hormone and clinical changes suggest that other factors than those studied are also involved in the genesis of hepatic cirrhosis.