Effects of short-term administration of low-dose rhGH on IGF-I levels in obesity and Cushing's syndrome: indirect evaluation of sensitivity to GH.
OBJECTIVE
To verify the hypothesis of an increased sensitivity to GH in obesity (OB) and Cushing's syndrome (CS).


METHODS
We studied the effects of short-term administration of low-dose rhGH on circulating IGF-I levels in patients with simple OB or CS and in normal subjects (NS).


METHODS
Nineteen women with abdominal OB aged (mean +/- s.e.m.) 38.2+/-3.1 years, body mass index 40.7+/-2.5 kg/m(2), waist to hip ratio 0.86+/-0.02, ten with CS (50.4+/-4.2 years, 29.7 +/- 3.3 kg/m(2)) and 11 NS (35.0+/-3.6 years, 20.5+/-0.5 kg/m(2)) underwent s.c. administration of 5 microg/kg per day rhGH at 2200 h for four days. Serum IGF-I, IGF-binding protein-3 (IGFBP-3), GH-binding protein (GHBP), insulin and glucose levels were determined at baseline and 12 h after the first and the last rhGH administration.


RESULTS
Basal IGF-I levels in NS (239.3+/-22.9 microg/l) were similar to those in OB (181.5+/-13.7 microg/l) and CS (229.0+/-29.1 microg/l). Basal IGFBP-3, GHBP and glucose levels in NS, OB and CS were similar while insulin levels in NS were lower (P<0.01) than those in OB and CS. In NS, the low rhGH dose induced a sustained rise of IGF-I levels (279.0+/-19.5 microg/l, P<0.001), a non-significant IGFBP-3 increase and no change in GHBP, insulin and glucose levels. In OB and CS, the IGF-I response to rhGH showed progressive increase (246.2+/-17.2 and 311.0+/-30.4 microg/l respectively, P<0.01 vs baseline). Adjusting by ANCOVA for basal values, rhGH-induced IGF-I levels in CS (299.4 microg/l) were higher than in OB (279.1 microg/l, P<0.01), which, in turn, were higher (P<0.05) than in NS (257.7 microg/l). In OB, but not in CS, IGFBP-3 and insulin levels showed slight but significant (P<0.05) increases during rhGH treatment, which did not modify glucose levels in any group; thus, in the OB patient group a significant fall in glucose/insulin ratio was observed.


CONCLUSIONS
Short-term treatment with low-dose rhGH has enhanced stimulatory effect on IGF-I levels in OB and, particularly, in hypercortisolemic patients. These findings support the hypothesis that hyperinsulinism and hypercortisolism enhance the sensitivity to GH in humans.
Maccario
M
M
Division of Endocrinology, Department of Internal Medicine, University of Turin, Italy.
Tassone
F
F
Gauna
C
C
Oleandri
S E
SE
Aimaretti
G
G
Procopio
M
M
Grottoli
S
S
Pflaum
C D
CD
Strasburger
C J
CJ
Ghigo
E
E
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D001824:Body Constitution; D015992:Body Mass Index; D002352:Carrier Proteins / Q000097:blood; D003480:Cushing Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007328:Insulin / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D001786:Blood Glucose; D002352:Carrier Proteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein