Studies on the Metabolic Clearance Rate, Apparent Distribution Space and Plasma Half-Disappearance Time of Unlabelled Human Growth Hormone in Normal Subjects and in Patients with Liver Disease, Renal Disease, Thyroid Disease and Diabetes Mellitus

Abstract. The metabolic clearance rate (MCR), half-disappearance time (T½ and apparent distribution space (DS) of unlabelled human growth hormone (HGH) have been studied using the priming dose – constant infusion technique. In 11 normal subjects MCR averaged 2.99 ml/kg/min., T½ 19.0 min. and DS 79.3 ml/kg. There were no differences between males and females and MCR was constant at HGH levels ranging from 5 to 50 ng/ml. In 10 out of 17 patients with chronic liver disease of varying severity MCR/kg was reduced below the lower limit of normal. TV₂ was prolonged in 15 of these patients. There was a very close correlation between MCR/kg and DS/kg in liver disease (r = 0.8219). Increased DS/kg accounted for the normal MCR/kg seen in some patients with severe hepatocellular failure. MCR/kg was markedly reduced in three patients'with chronic renal failure. T7₂ and DS/kg were both significantly increased in this group (48.0 min. and 117.0 ml/kg, respectively). MCR/kg and T7₂ were normal in one patient with the nephrotic syndrome but normal glomerular filtration rate. MCR/kg was not significantly different from normal in patients with thyrotoxicosis, myxoedema and uncontrolled diabetes mellitus, despite the fact that T½ shorter than normal in thyrotoxicosis and longer than normal in myxoedema. It is suggested that HGH does not normally diffuse freely from the vascular to extravascular extracellular fluid, and that normally a substantial concentration gradient exists between the vascular and extravascular compartments; under these circumstances, the liver and kidneys are the major sites of HGH metabolism. In hepatic and renal failure, this gradient is reduced and extravascular degradation sites may assume more importance in the metabolism of growth hormone. Acute fluctuations in the peripheral blood concentrations of growth hormone indicate alterations in secretion rate and not alterations in metabolism.