Acute and chronic effects of human recombinant GH (hrGH) on adrenal steroidogenesis in children affected with isolated GH deficiency (IGHD).
In a previous study we demonstrated that, in children affected with isolated GH deficiency, an acute high-dose human recombinant GH (hrGH) treatment increases the 11-deoxycortisol and induces an IGF-I responsiveness to ACTH. The aim of the present study was to reevaluate, in the same children, the adrenal and IGF-I responsiveness to ACTH after a chronic replacement-dose GH therapy. Ten children (seven males and three females, mean age 7 years) affected with isolated GH deficiency underwent a synthetic ACTH 1-17 test before and after sc administration of human recombinant GH at a dose of 0.6 UI/kg/week for 3 months. After therapy, the 11-deoxycortisol responsiveness to ACTH significantly decreased compared with that observed after acute treatment (P < 0.001), and so it returned to baseline. No differences were detected in the responsiveness to ACTH of cortisol, dehydroepiandrosterone-sulphate, D4-androstenedione, and 17-hydroxyprogesterone. On the other hand, the chronic treatment induced an IGF-I responsiveness to ACTH (P < 0.001). In conclusion, our study demonstrates that, in isolated GH deficiency, replacement doses of hrGH do not modify the adrenal steroid basal levels or its responsiveness to ACTH, whereas both replacement and high doses of hrGH induce an IGF-I responsiveness to ACTH.
Rossi
E
E
Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Italy.
Merola
B
B
Longobardi
S
S
Esposito
V
V
Tommaselli
A P
AP
Colao
A
A
Lombardi
G
G
D015068:17-Ketosteroids / Q000652:urine; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D001827:Body Height; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy* / Q000503:physiopathology; D013006:Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012016:Reference Values
D015068:17-Ketosteroids; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D000324:Adrenocorticotropic Hormone; D013006:Growth Hormone; C028238:ACTH (1-17)