The effect of alcohol on the hepatic metabolism of hormones

Alcoholism may be associated with a wide range of metabolic and endocrine complications. These include a hypermetabolic state, similar in some respects to thyrotoxicosis; hypoglycaemia; diabetesmellitus; ketoacidosis, lactic acidosis; hyperuricaemia; isolated ACTH deficiency ; glucocorticoid excess; disturbed water and electrolyte metabolism; hypocalcaemia and magnesium depletion; and androgen deficiency and feminization [ 1,2] . These complications may arise from actions of ethanol on the liver and/or the endocrine glands, from nutritional deficiencies associated with alcoholism or from liver damage (alcoholic fatty liver, hepatitis or cirrhosis). It has often proved difficult or impossible to disentangle the pathogenesis of these endocrine complications and much work remains to be done. The direct role of ethanol itself at hepatic or peripheral sites has not always been completely defined. For example, in the sex hormone disorder in alcoholic men, the endocrine syndrome results from a combination of the direct effects of alcohol on liver or endocrine glands, and less specific effects due to varying degrees of liver damage. Ethanol is principally metabolized via alcohol dehydrogenase, a cytoplasmic enzyme, to acetaldehyde, and then via aldehyde dehydrogenase, a mitochondrial enzyme, to acetate [3, 41. Its metabolism leads to the generation of excess reducing equivalents (NADH) in cytoplasm, and (with the operation of shuttle mechanisms) in mitochondria. The altered redox state of the liver leads to hypoglycaemia in the fasting state principally by inhibiting pyruvate carboxylase (a key enzyme in gluconeogenesis) when glycogen stores are low and maintenance of the blood glucose concentration requires gluconeogenesis. In alcohol-induced fasting hypoglycaemia this is the principle mechanism of lowered blood glucose. Insulin levels are often inappropriately high, which may in part result from &cell stimulation by markedly elevated glucagon levels which occur in ineffectual response to the fall in blood sugar. In addition alcohol apparently potentiates insulin secretion stimulated by glucose, arginine and tolbutamide [S] . It has recently been recognized that this can lead to reactive hypoglycaemia after alcohol and a glucose load are ingested together [ S ] . Although the liver is the major site of insulin uptake and degradation, it is doubtful whether impairment of this mechanism has any part to play in this syndrome. Generation of excess reducing equivalents may also lead to lactic acidaemia and keto-