A B S T R A C T The metabolic clearance rate (MCR) of human growth hormone (HGH) was determined by the constant infusion to equilibrium technique utilizing HGH-5I. 22 control subjects had a MCR of 229 ±52 ml/min (mean ±sD). No difference was evident between sexes, or between various age groups. Patients with acromegaly demonstrated normal MCR's. Moreover, acute elevations of plasma growth hormone concentrations in normal subjects did not alter the MCR of HGH. The MCR was relatively constant from day to day and within the day when subjects were evaluated in the supine position. In contrast, the assumption of the upright position was associated with a mean 24% decrease in the MCR.These results were contrasted with the MCR of HGH observed in a small number of patients with altered thyroid function or diabetes mellitus. In six patients with hypothyroidism the MCR (131 ±36 ml/min) was significantly decreased (P < 0.001); whereas the MCR in eight patients with hyperthyroidism (240 ±57 ml/min) did not differ from control subjects. The MCR in eight patients with insulin-independent diabetes mellitus (IID) (185 ±41 ml/min) and in eight patients with insulin-dependent diabetes mellitus (IDD) (136 ±31 ml/min) were significantly different from control subjects (P = < 0.05 and P = < 0.001, respectively).These data were interpreted to indicate that the plasma HGH-removing mechanism(s) is not saturated at physiologic plasma HGH of clearance from the plasma, and that the estimation of the MCR of HGH may help clarify the mechanism of abnormal plasma HGH responses to various stimuli.Production rates of HGH (PR) in control subjects (347 ±173 mug/min) were contrasted with hyperthyroid patients (529 ±242 mitg/min, P < 0.05), hypothyroid patients (160 ±69 m/g/min, P < 0.02), lID (245 ±100 m/g/min, NS), and IDD (363 ±153 mug/min, NS). Considerable variability in the determination of the concentrations of immunoprecipitable HGH-l`I and endogenous plasma HGH concentrations was encountered at apparent equilibrium conditions. Since both factors are necessary for the PR calculations, the wide 95% confidence limits of the PR's did not permit a clear interpretation of the significance of these observations. INTRODUCTION Investigators examining the physiologic regulation of plasma human growth hormone (HGH) have been aware that diverse stimuli (1-9) elicit changes in plasma HGH concentrations. Such changes in plasma levels alone, moreover, do not distinguish between the separate contributions of pituitary HGH release and HGH clearance from the plasma, both of which are responsible for a change in plasma concentration.The plasma disappearance of single intravenous injections of radioisotopically labeled HGH has been analyzed to define the distribution and turnover of HGH in humans (10-12). The fractional turnover and production rates of HGH in these studies were derived from calculations which assume first order kinetics and steadystate conditions. Some of the radioisotopic plasma disappearance curves in the literature (10, 11), however, do ...

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