Hyperglucagonaemia in cirrhosis. Relationship to hepatocellular damage.

Plasma glucagon and growth hormone concentrations were measured fasting and after oral glucose in 19 patients with portal vein block with extensive portal-systemic shunting but minimal liver cell damage, 11 cirrhotic patients and 12 matched control subjects. Portal vein block patients and controls had similar fasting glucose and glucagon levels (glucose 3.8 +/- 0.1 mmol/l VS control 3.4 +/- 0.1 mmol/l (mean +/- SEM); glucagon 57.5 +/- 9.1 pg/ml VS control 51.3 +/- 7.8 pg/ml). Cirrhotic patients were hyperglycaemic (cirrhosis 4.3 +/- 0.2 mmol/l VS control 3.4 +/- 0.1 mmol/l, p < 0.01) with significantly elevated glucagon levels (167.3 +/- 61.1 pg/ml VS control 51.3 +/- 7.8 pg/ml, p < 0.05), which suppressed towards control values after oral glucose. There was no correlation between fasting plasma glucagon levels and the degree of portal-systemic shunting in cirrhotic patients. There was a strong correlation between fasting plasma glucagon concentrations and aspartate transaminase levels (r = 0.68; p < 0.01) in cirrhotic and portal vein block patients. Significant elevations of growth hormone were seen only in cirrhotic patients. It is concluded that hyperglucagonaemia is a feature of hepatocellular damage rather than portal-systemic shunting but the relationship between elevated glucagon and growth hormone concentrations and carbohydrate intolerance in cirrhosis remains unclear.

Amenorrhoea, body weight and serum hormone concentrations, with particular reference to prolactin and thyroid hormones in anorexia nervosa.

Twenty women with anorexia nervosa were investigated at varying stages during weight gain. Basal prolactin and TSH and prolactin responses to TRH were normal and unrelated to body weight. LH, FSH and 17 beta oestradiol were low in emaciated patients and rose with weight gain. There was no correlation between serum gonadotrophin and prolactin concentrations. T3 and T4 concentrations were low but T3 rose with weight gain during refeeding over 4-6 weeks, whereas T4 remained low. A positive correlation was found between the TSH response to TRH and body weight. The abnormalities in the hypothalamic-pituitary-thyroid axis were similar to those seen in a variety of chronic illnesses and appear to be unrelated to the amenorrhoea. The failure of restoration of normal function at least after short-term refeeding requires further investigation. It was concluded that the amenorrhoea in anorexia nervosa is not associated with changes in prolactin secretion but is determined primarily by changes in the hypothalamic-pituitary-gonadal axis. These changes are induced largely by nutritional factors but psychological factors may also be involved.

Serum prolactin in liver disease and its relationship to gynaecomastia.

Serum immunoreactive prolactin was measured in 150 patients with liver disease of varying aetiology and severity and in 45 control subjects. The upper limit of the reference range for serum prolactin was 331 mU/l. Eighteen patients with liver disease (12%) had unexplained hyperprolactinaemia. No relationship existed between the prolactin value and the sex of the patient, the aetiology of the liver disease, the severity of the liver disease, or the presence of gynaecomastia. The cause of the hyperprolactinaemia in patients with liver disease and its clinical implications need further investigation.

Comparison of maternal serum and urinary oestrogen determinations as indicators of fetal well-being.

Serum oestrogen concentration and urinary oestrogen excretion were measured in 134 women in the last trimester of pregnancy. An automated fluorimetric method was used for urinary oestrogens and a radioimmunoassay which measures both free and conjugated oestrogens, with the exception of sulphates, was employed for serum. Pregnancies were classified into a 'normal' or 'abnormal' group according to the clinical state of the baby at birth. The range of values for both serum and urinary oestrogens was wide at each stage of gestation and the mean values in the two groups were not significantly different. It was concluded that for a valid indication of fetal well-being serial determinations were essential, and that serum and urinary oestrogens were of comparable predictive value. Expressing the urinary results in terms of creatinine excretion did not improve their predictive value.

Use of clomiphene and luteinizing hormone/follicle stimulating hormone-releasing hormone in investigation of ovulatory failure.

A luteinizing hormone/follicle-stimulating hormone-releasing hormone (LH/FSH-RH) test was performed in 70 women with amenorrhoea or anovulatory infertility, or both, and a clomiphene stimulation test was also performed in 24 of these patients. Most patients responded to LH/FSH-RH with significant increases in LH and FSH. In women with gonadal dysgenesis or premature ovarian failure exaggerated responses were observed after LH/FSH-RH and there was no change in high basal LH levels after clomiphene. Patients with absent or impaired responses to LH/FSH-RH failed to respond to clomiphene. All patients with anovulatory menstrual cycles responded to both LH/FSH-RH and clomiphene, while seven out of 13 amenorrhoeic patients with a normal LH/FSH-RH response showed an early LH rise during clomiphene treatment and six were unresponsive. These results suggest a difference between the two groups at hypothalamic level with consequent therapeutic implications.