Plasma integrated concentration of growth hormone after recombinant human growth hormone injection. Implications for determining an optimal dose.
OBJECTIVE
To evaluate the effect of a standard dose of injected recombinant growth hormone on the integrated concentrations of growth hormone and insulin.


METHODS
Integrated concentrations were studied in patients receiving growth hormone therapy before and on the day of injection.


METHODS
Pediatric endocrine clinic and diagnostic unit.


METHODS
Twelve growth hormone-deficient patients with poor linear growth and deficient growth hormone response to provocative stimulation and/or 24-hour integrated concentration.


METHODS
Patients received subcutaneous injections of 0.06 mg/kg of growth hormone three times a week in the evenings at approximately 8 PM. Integrated concentrations were measured again approximately 6 months after the start of therapy at the time of a growth hormone injection.


RESULTS
Mean growth hormone dose administered was 2.0 +/- 0.5 mg. Integrated concentration of growth hormone was 2.2 +/- 0.9 micrograms/L before therapy. The integrated concentration of growth hormone after treatment (14.6 +/- 4.2 micrograms/L) was significantly higher than that before treatment and that of normally growing children (P < .001). After injection, peak growth hormone level was 53.7 +/- 24.1 micrograms/L; time to peak growth hormone level, 4.8 +/- 1.2 hours; constant of elimination, 0.24 +/- 0.06 per hour; half life, 3.0 +/- 0.7 hours; area under the curve, 328 +/- 85 (microgram.h)/L; clearance rate, 107.6 +/- 34.3 mL/min (3.2 +/- 0.8 mL/min per kilogram based on weight, 95.2 +/- 24.2 mL/min per meter squared based on surface area). There was no relationship between integrated concentration of growth hormone or pharmacokinetic variables after treatment and the growth response to 6 months' therapy. Integrated concentration of insulin before treatment was 19.0 +/- 10.9 mU/L, which was significantly lower than that after injection of growth hormone (33.4 +/- 9.5 mU/L; n = 9, P < .0008).


CONCLUSIONS
Integrated concentrations of growth hormone after an injection of 0.06 mg/kg of growth hormone are considerably higher than spontaneous integrated concentrations of growth hormone observed in normally growing children, and associated with a rise in insulin secretion. These changes may be pertinent in patients with underlying insulin resistance or when higher doses of growth hormone are used for therapy.
Chalew
S A
SA
Division of Pediatric Endocrinology, University of Maryland School of Medicine, Baltimore 21201.
Phillip
M
M
Kowarski
A A
AA
D000293:Adolescent; D000365:Age Determination by Skeleton; D001827:Body Height; D001830:Body Surface Area; D001835:Body Weight; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D013006:Growth Hormone / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D008657:Metabolic Clearance Rate; D011627:Puberty; D011863:Radioimmunoassay; D013997:Time Factors
D007328:Insulin; D013006:Growth Hormone