Effects of morning cortisol replacement on glucose and lipid metabolism in GH-treated subjects.
OBJECTIVE
Insulin resistance is a frequent consequence of GH replacement therapy but patients on GH replacement therapy often also have replacement of other hormone deficiencies which theoretically could modify the metabolic effects of GH. In particular, cortisol replacement if given in supra physiologic doses immediately before the evaluation of insulin sensitivity could influence insulin sensitivity. The aim of this study was thus to evaluate the effect of morning cortisol replacement given prior to a euglycaemic clamp combined with infusion of [3-(3)H]glucose and indirect calorimetry on glucose and lipid metabolism.


METHODS
Ten GH/ACTH-deficient adults received, in a double-blind manner, either cortisol (A) or placebo (B) before the clamp whereas five GH-deficient-ACTH-sufficient adults participated in a control (C) clamp experiment. All subjects received GH replacement therapy.


RESULTS
Serum cortisol levels were significantly higher after cortisol than after placebo (324+/-156 vs 132+/-136 mmol/l; P=0.006) and similar to controls (177+/-104 mmol/l). As a measure of the biological effect of cortisol, eosinophil leukocyte counts in peripheral blood decreased (164+/-91 x 10(9)/l vs 216+/-94 x 10(9)/l; P=0.04). Cortisol replacement had no significant effect on insulin-stimulated glucose uptake (11.8+/-1.8 vs 13.2+/-3.9 micromol/kg min), either on glucose oxidation or on glucose storage. There was also no significant effect of cortisol on fasting endogenous glucose production and no effect was seen on serum free fatty acid concentrations.


CONCLUSIONS
Administration of cortisol in the morning before a clamp cannot explain the insulin resistance seen with GH replacement therapy.
Segerlantz
Mikael
M
Department of Endocrinology, University Hospital MAS, S-20502 Malmo, Sweden. Mikael.Segerlantz@telia.com
Bramnert
Margareta
M
Thomasson
Ronnie
R
Manhem
Per
P
Laurila
Esa
E
Groop
Leif C
LC
D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002153:Calorimetry, Indirect; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D013006:Growth Hormone / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000172:deficiency; D006801:Humans; D006854:Hydrocortisone / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010900:Pituitary Diseases / Q000188:drug therapy / Q000503:physiopathology; D011506:Proteins / Q000378:metabolism; D015203:Reproducibility of Results
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D008055:Lipids; D011506:Proteins; D019382:Human Growth Hormone; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; D006854:Hydrocortisone