Effect of growth hormone deficiency and recombinant hGH (rhGH) replacement on the hypothalamic-pituitary-adrenal axis in children with idiopathic isolated GH deficiency.
OBJECTIVE
Recombinant hGH (rhGH) therapy may unmask central hypoadrenalism in adults with organic GH deficiency (GHD), likely by normalizing 11beta-hydroxysteroid dehydrogenase type 1 isoenzyme (11betaHSD1) activity and reducing cortisone to cortisol conversion. The aim of the present study was to evaluate the hypothalamic-pituitary-adrenal (HPA) axis in children with idiopathic isolated GHD and normal pituitary magnetic resonance imaging (MRI) both before and during rhGH therapy.


METHODS
This was a single-centre study of 10 consecutive children [five males and five females, mean age: 12.2 +/- 1.0 year]. Evaluation was performed at baseline and on rhGH (mean duration: 10.9 +/- 2.9 months, mean dose: 0.030 +/- 0.002 mg/kg bw/day).


METHODS
HPA function was assessed by serum cortisol levels before and after appropriate provocative stimuli, that is, 1 microg ACTH test (N = 5 patients) or insulin tolerance test (ITT, N = 5 patients), evaluating all children with the same stimulation test both before and during rhGH therapy. Central hypoadrenalism was excluded by the presence of either a peak of > 500 nmol/l or a rise in cortisol levels of > 200 nmol/l, after both tests.


RESULTS
On rhGH therapy, serum IGF-I levels normalized, while serum cortisol and ACTH levels did not significantly differ from those recorded at baseline. The mean serum cortisol peak after both provocative tests was not significantly different on rhGH therapy and at baseline (498 +/- 41 vs. 580 +/- 35 nmol/l, respectively, P = 0.06), the mean cortisol rise being 280 +/- 45 and 270 +/- 36 nmol/l on rhGH and at baseline, respectively.


CONCLUSIONS
According to the diagnostic criteria, no child became hypoadrenal on rhGH, contrary to what observed in patients with organic GHD, further supporting the view that only in patients with organic multiple pituitary hormone deficiency GHD masks the presence of a hidden central hypoadrenalism.
Giavoli
Claudia
C
Endocrine Unit, Department of Medical Sciences, University of Milan, Milan, Italy.
Bergamaschi
Silvia
S
Ferrante
Emanuele
E
Ronchi
Cristina L
CL
Lania
Andrea G
AG
Rusconi
Roberto
R
Spada
Anna
A
Beck-Peccoz
Paolo
P
D000293:Adolescent; D002648:Child; D004393:Dwarfism, Pituitary / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism*; D011863:Radioimmunoassay
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone