Consequences of lifetime isolated growth hormone (GH) deficiency and effects of short-term GH treatment on bone in adults with a mutation in the GHRH-receptor gene.
OBJECTIVE
Growth hormone (GH) influences bone mass maintenance. However, the consequences of lifetime isolated GH deficiency (IGHD) on bone are not well established. We assessed the bone status and the effect of 6 months of GH replacement in GH-naive adults with IGHD due to a homozygous mutation of the GH-releasing hormone (GHRH)-receptor gene (GHRHR).


METHODS
We studied 20 individuals (10 men) with IGHD at baseline, after 6 months of depot GH treatment, and 6 and 12 months after discontinuation of GH. Quantitative ultrasound (QUS) of the heel was performed and serum osteocalcin (OC) and C-terminal cross-linking telopeptide of type I collagen (ICTP) were measured. QUS was also performed at baseline and 12 months later in a group of 20 normal control individuals (CO), who did not receive GH treatment.


RESULTS
At baseline, the IGHD group had a lower T-score on QUS than CO (-1.15 +/- 0.9 vs.-0.07 +/- 0.9, P < 0.001). GH treatment improved this parameter, with improvement persisting for 12 months post-treatment (T-score for IGHD = -0.59 +/- 0.9, P < 0.05). GH also caused an increase in serum OC (baseline vs. pGH, P < 0.001) and ICTP (baseline vs. pGH, P < 0.01). The increase in OC was more marked during treatment and its reduction was slower after GH discontinuation than in ICTP.


CONCLUSIONS
These data suggest that lifetime severe IGHD is associated with significant reduction in QUS parameters, which are partially reversed by short-term depot GH treatment. The treatment induces a biochemical pattern of bone anabolism that persists for at least 6 months after treatment discontinuation.
de Paula
Francisco J A
FJ
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Brazil.
Góis-Júnior
Miburge B
MB
Aguiar-Oliveira
Manuel H
MH
Pereira
Francisco de A
Fde A
Oliveira
Carla R P
CR
Pereira
Rossana M C
RM
Farias
Catarine T
CT
Vicente
Tábita A R
TA
Salvatori
Roberto
R
D000328:Adult; D002111:Calcaneus / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D024042:Collagen Type I; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides; D011347:Procollagen / Q000097:blood; D018013:Receptors, Neuropeptide / Q000235:genetics*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics*; D014463:Ultrasonography
D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D019382:Human Growth Hormone; C048250:somatotropin releasing hormone receptor