Disappearance Rate of Endogenous and Exogenous Human Growth Hormone in Man

Following hypophysectomy the t1/2 of endogenous HGH in an acromegalic giant (R.C.) was 50 min. HGH fell from a preoperative level of 100 ng/ml to <1 ng/ml 5 days later. In the same patient, the half-times of exogenous Raben HGH administered as a single bolus (275 and 200 μg) were 25.7 and 26.9 min (2 and 9 months post hypophysectomy) and were similar to values reported by others. The t1/2 of HGH in 2 patients with long-standing panhypopituitarism were 15.3 and 14.4 min. In view of the discrepancy observed between the t1/2 of endogenous and exogenous HGH, R.C. was given a 90-min infusion of HGH (4 μg/min), following which the t1/2 was 51.4 min. The distribution space of HGH ranged from 5.2 to 11.2% body wt, and in patient R.C. was similar when estimated from the single bolus or continuous infusion technique (5.2 and 5.7% body wt, respectively). The metabolic clearance rate was 80 ml/min, which approximates that of human placental lactogen obtained by the same technique. It was concluded that (a) the single bolus technique may not be valid for estimating t1/2 of polypeptide hormones that turn over rapidly; (b) the turnover rate of HGH may be slower than previously suggested; (c) exogenous and endogenous HGH have identical half-times when time is allowed for the former to equilibrate; (d) the slow clearance rate of HGH in the acromegalic patient raises the possibility that alterations in the degradation process in pathological conditions may influence the concentration of the hormone in plasma; (e) in the absence of knowledge of the clearance rate, caution must always be used in accepting a serum concentration as being indicative of a secretion rate.