Can auxology, IGF-I and IGFBP-3 measurements followed by MRI and genetic tests replace GH stimulation tests in the diagnosis of GH deficiency in children?
OBJECTIVE
GH levels < 10 ng/ml in response to two different GH stimulation tests (GHSTs) are traditionally used to identify children with GH deficiency (GHD). Since GHSTs are imprecise, other diagnostic tools have been proposed. We assessed whether auxology, IGF-I and IGFBP-3 measurements followed by brain MRI and genetic analysis can replace the current diagnostic approach.


METHODS
Fifty-three children diagnosed with GHD by two different GHSTs. GH-1 gene was sequenced.


RESULTS
At presentation, 17% of patients were with height above -1.5 SD and 28% above -2.0 SD; 50% had IGF-1 concentration above -1.5 SD and 58% above -2.0 SD; 59% had pituitary anomalies demonstrated by MRI. Fourteen patients harbored the heterozygous R183H mutation, one patient had the N47D mutation and one had a novel F25Y mutation in GH-1. Using cut-off levels of -1.5 SD for height, IGF-I and IGFBP-3 excluded the diagnosis of GHD in 17, 68 and 79% of the children, respectively; a cut-off of -2 SD excluded 28, 88 and 96%, respectively. Further brain MRI and genetic tests excluded 81-96% and 96-100%, respectively, of children currently diagnosed with GH.


CONCLUSIONS
Use of the tested approach, which avoids carrying out two GHSTs, would exclude most children currently diagnosed with GHD. Until better tools become available, we recommend identifying GHD in children by an integrated approach combining phenotype, auxological parameters, hormonal measurements and two separate GHSTs, with MRI and genetic tests to support the diagnosis.
Tenenbaum-Rakover
Yardena
Y
Pediatric Endocrine Unit, Ha 'Emek Medical Center, Afula, Israel. rakover_y@clalit.org.il
Hujeirat
Yasir
Y
Admoni
Osnat
O
Khayat
Morad
M
Allon-Shalev
Stavit
S
Hess
Ora
O
D001827:Body Height; D002648:Child; D002675:Child, Preschool; D005260:Female; D005820:Genetic Testing; D006130:Growth Disorders / Q000097:blood / Q000175:diagnosis*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007223:Infant; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male
D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I