Partial growth hormone insensitivity in childhood.
There appears to be a continuum of GH-responsiveness, ranging from complete GH-resistance in Laron syndrome to normal GH-sensitivity. Partial GHI is suggested by findings at both ends of this spectrum; some patients with Laron-type dwarfism are less severely affected by their GHI than others (Savage et al, 1993; for a review, see Savage et al, 1995) and some short, non-GH-deficient, children have reduced responsiveness to GH. Among children with ISS, we have identified a subgroup where defects at the level of the GH receptor lead to a partial-GHI syndrome (Carlsson et al, 1994; Attie et al, 1995; Goddard et al, 1995). Partial-GHI may explain the growth failure in some children who do not meet the criteria for GHD. So far, the clinical evaluation of short children has been focused on the exclusion or demonstration of GHD. The diagnosis of GHD at present requires that stimulated or spontaneous GH concentrations should fail to reach a certain, arbitrarily determined level. This assumes that GH-sensitivity is equal in all subjects, with the exception of rare cases with Laron syndrome. The diagnosis of GHD is in itself controversial, and it has been suggested that GH testing should be supplemented by other measures such as auxological evaluation and measurement of other components of the GH/IGF-I axis (Rosenfeld et al, 1995). However, the fact that some short children have partial-GHI suggests that both GH secretion and GH responsiveness should be taken into consideration when investigating the cause of short stature (Figure 5). Many short children do not have GHD per se, but may be short due to inadequate GH stimulation because of reduced GH-sensitivity.
Carlsson
L M
LM
Department of Research, Metabolic Unit, Kantonsspital, Basel, Switzerland.
D000367:Age Factors; D001323:Autoantibodies / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood / Q000378:metabolism; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000209:etiology* / Q000503:physiopathology; D019382:Human Growth Hormone / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D009154:Mutation; D011986:Receptors, Somatotropin / Q000097:blood / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D014424:Turner Syndrome / Q000097:blood
D001323:Autoantibodies; D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein