Metabolic clearance and production rates of human growth hormone

Abstract

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 ...

Growth Hormone: Metabolic Clearance Rates, Integrated Concentrations, and Production Rates in Normal Adults and the Effect of Prednisone

“…Previous investigators (19)(20)(21) have documented that increased GH levels result when estrogen is given before arginine or insulin stimulation. However, Taylor et al (4) and MacGillivray et al (5) found no difference between males and females when using multiple single samples to calculate production rates. Frasier, Hilburn, and Smith (22) suggested that there was no significant difference between adolescent males and females in their GH response to insulininduced hypoglycemia.…”

“…Urinary methods, as used for many steroids, are not applicable for growth hormone (GH) production studies because of the insignificant amount of GH excreted in urine (1). Although the constant intravenous infusion method of Tait (2) has been utilized to determine the metabolic clearance rate of GH (3)(4)(5), a truly accurate production rate cannot be calculated from the data obtained because plasma GH concentrations may fluctuate rapidly. Therefore, the mean GH concentration obtained from multiple samples collected over only a 3.5-4 hr period by Taylor, Finster, and Mintz (4) and used to determine production rate does not necessarily represent the mean GH concentration that is present in serum over a 24 hr period.…”

“…Although the constant intravenous infusion method of Tait (2) has been utilized to determine the metabolic clearance rate of GH (3)(4)(5), a truly accurate production rate cannot be calculated from the data obtained because plasma GH concentrations may fluctuate rapidly. Therefore, the mean GH concentration obtained from multiple samples collected over only a 3.5-4 hr period by Taylor, Finster, and Mintz (4) and used to determine production rate does not necessarily represent the mean GH concentration that is present in serum over a 24 hr period. The same criticism applies to the studies of MacGillivray, Frohman, and Doe (5), who drew serum samples from fasting and resting individuals every 20 min during a 6-7 hr period and utilized a mean of these samples to calculate GH production rates.…”

Metabolic clearance of recombinant human growth hormone in health and chronic renal failure.

“…In previous studies the metabolic clearance rate (MCR) of exogenous GH in healthy human subjects ranged from 143 to 329 ml/min (6)(7)(8)(9)(10)(11)(12), and plasma half-life ranged from 15 to 51 min (7,(12)(13)(14)(15). In patients with reduced renal function, reduced MCR (12,16) and normal (17) or prolonged (12) plasma half-lives of GH have been reported.…”

Relationship between Thyroid Functions and Urinary Growth Hormone Secretion in Patients with Hyper- and Hypothyroidism.

“…The discrepancy between serum and urinary GH responses to GRH in the hyperthyroid patients raises the possibility that urinary clearance of GH may be increased in hyperthyroid states, as previously reported in cortisol [21]. However, previous studies were not able to demonstrate an accelerated metabolic clearance rate for GH in patients with thyrotoxicosis [22,23]. Further studies are required to elucidate the metabolic clearance of GH in hypo-and hyperthyroid states.…”