Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children.
BACKGROUND
We recently showed that, in IGF-based GH therapy, the IGF-I target chosen affects GH dose requirements, and higher IGF-I targets are associated with more robust growth parameters.


OBJECTIVE
The objective of the study was to compare the response of GH-deficient (GHD) vs. idiopathic short-stature (ISS) children to IGF-based GH therapy.


METHODS
This was a 2-yr, open-label, randomized trial.


METHODS
The setting was multicenter and outpatient.


METHODS
Prepubertal short children [height sd score (SDS) < -2] with low IGF-I levels (<or=-1 SDS), subclassified based on the peak stimulated serum GH concentration at baseline, into two subgroups: GHD (n = 63, GH < 7 ng/ml) and ISS (n = 102, GH >or= 7 ng/ml).


METHODS
Patients were randomized 2:2:1 to three treatment groups: IGF-I target of 0 SDS (IGF0T), 2 SDS (IGF2T), or a conventional weight-based GH dosing of 40 microg/kg x d (Conv).


METHODS
Change in (Delta) height SDS, IGF-I SDS, and GH dose was measured.


RESULTS
ISS subjects required higher GH doses than GHD patients in the IGF2T (but not IGF0T) arm (medians 119 and 65 microg/kg x d, respectively), indicating that ISS represents a partial GH-insensitive state that manifests during treatment with higher doses of GH. GHD children grew more than those with ISS in both IGF-targeted dosage groups despite similar IGF-I levels (suggesting a degree of IGF insensitivity in ISS subjects): Delta height SDS of 2.04 +/- 0.17 for GHD and 1.33 +/- 0.09 for ISS groups in IGF2T, 1.41 +/- 0.13 for children with GHD, and 0.84 +/- 0.07 for those with ISS in IGF0T.


CONCLUSIONS
IGF-based GH dosing is clinically feasible in both GHD and ISS patients, although GH dose requirements and auxological outcomes are distinct between these groups. This suggests a degree of both GH and IGF insensitivity in subjects with ISS that requires specific management strategies to optimize growth during GH therapy.
Cohen
Pinchas
P
Pediatric Endocrinology, Mattel Children's Hospital at University of California, Los Angeles, 10833 Le Conte Avenue, MDCC 22-315, Los Angeles, California 90095, USA. hassy@mednet.ucla.edu
Germak
John
J
Rogol
Alan D
AD
Weng
Wayne
W
Kappelgaard
Anne-Marie
AM
Rosenfeld
Ron G
RG
D001827:Body Height / Q000187:drug effects; D015992:Body Mass Index; D001940:Breast / Q000033:anatomy & histology; D002648:Child; D002675:Child, Preschool; D004393:Dwarfism, Pituitary / Q000188:drug therapy*; D005260:Female; D006128:Growth / Q000187:drug effects / Q000502:physiology*; D013006:Growth Hormone / Q000097:blood / Q000627:therapeutic use; D019382:Human Growth Hormone / Q000097:blood* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D013002:Somatomedins / Q000494:pharmacology / Q000627:therapeutic use*; D013737:Testis / Q000033:anatomy & histology
D013002:Somatomedins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone