Clinical diagnoses of children with extremely short stature and their response to growth hormone.

This study was undertaken to determine the prevalence of clinical diagnoses in a group of children with extremely short stature (standard deviation score for height, < -2.5) and to determine whether the classification might help in predicting response to human growth hormone (hGH) treatment. We classified 49 children referred consecutively to our outpatient clinic for evaluation of short stature with heights < -2.5 standard deviation score and bone ages < 9 years for girls or < 10 years for boys (to avoid an effect of puberty on the response to hGH). The diagnostic categories were growth hormone (GH) deficiency, constitutional delay, familial short stature, and primordial short stature. After referral, Turner syndrome was diagnosed in two children. The remaining 47 children were classified according to primary criteria, considered essential for the diagnosis, and secondary criteria, considered necessary but of lesser importance. There were five children, four children, no children, and one child classified, respectively, with GH deficiency, constitutional delay, familial short stature, and primordial short stature by using the most rigorous definitions of the diagnoses. There was significant overlap in the diagnoses other than GH deficiency. Growth hormone deficiency defined by the primary criterion of peak stimulated GH values < 5 micrograms/L was the most definitive. Of the 47 children, 7 were classified as GH deficient by this criterion and 5 were classified as GH deficient by the primary and secondary criteria. The mean pretreatment growth rate (3.1 +/- 1.9 cm/yr) of the group with stimulated GH values < 5 micrograms/L was significantly less than that in the other groups (4.2 +/- 1.5 cm/yr). The mean growth rate of the children with GH deficiency during treatment with hGH was greater than that in the other groups and was 3.4 times greater than the pretreatment growth rate. The mean growth rate of children in the other groups during hGH treatment was twofold greater than the pretreatment growth rate. We conclude that except for GH deficiency, children with an extreme degree of short stature are not easily classified by standard diagnostic criteria, and that most short children have a positive response to hGH therapy regardless of the diagnosis; therefore a specific clinical diagnosis should not be used to exclude children from hGH therapy.