Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters.
OBJECTIVE
We examined the effects of different doses of GH on insulin-like growth factor I (IGF-I), IGF binding protein 3 (IGFBP-3), body composition, energy expenditure, and various metabolites in GH deficient adults, in order to approach a metabolically appropriate GH dosage in young GH deficient adults.


METHODS
Ten GH deficient patients (age 21-43) were studied after 4 weeks without GH followed by three consecutive 4-week periods, where the patients received in a fixed order GH 1, 2 and 4 IU/m2 s.c. per day. At the end of each period the patients were hospitalized for a 24-hour examination.


RESULTS
Mean 24-hour levels of GH (mIU/l) were 2.7 +/- 0.3 (0 GH), 7.2 +/- 0.9 (1), 10.8 +/- 1.5 (2) and 18.9 +/- 2.7 (4 IU/m2) (mean +/- SEM) (P < 0.01). Likewise, IGF-I levels increased dose dependently from 61 +/- 21 to 206 +/- 65, 260 +/- 70 and 468 +/- 171 micrograms/l (P < 0.05); serum IGF-I in an age and sex matched control group was 248 +/- 25 micrograms/l. Corresponding serum IGFBP-3 levels also increased from 1860 +/- 239 to 3261 +/- 379, 3762 +/- 434 and 4384 +/- 652 micrograms/l (P = 0.01) respectively. Significant increases in diurnal serum insulin levels after 4 IU/m2 were recorded, whereas plasma glucose levels remained unchanged. Lipid intermediates increased dose independently during GH administration. GH caused a significant increase in resting energy expenditure, whereas the respiratory exchange ratio was unaltered. Fat mass was increased without GH therapy and decreased during the study. Four patients made complaints during 4 IU/m2 GH administration, probably related to GH induced fluid retention.


CONCLUSIONS
Based primarily on IGF-I and IGFBP-3 levels our data suggest that a GH replacement dose in young GH deficient adults in the order of 1-2 IU/m2 per day is adequate. This is a relatively low dose as compared to dose regimens in children and adolescents.
Møller
J
J
Medical Department M (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark.
Jørgensen
J O
JO
Lauersen
T
T
Frystyk
J
J
Naeraa
R W
RW
Orskov
H
H
Christiansen
J S
JS
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency* / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000187:drug effects* / Q000378:metabolism; D008297:Male
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone