ESPE Abstracts

The diagnosis of growth hormone deficiency (GHD) is primarily clinical and usually includes: short stature but virtually always growth failure, perhaps some physical findings that accompany syndromic causes, and alterations in body composition and in the regional distribution of body fat. Laboratory testing, whether static or dynamic, and medical imaging are mostly confirmatory to the clinical diagnosis. Biochemical laboratory testing for GH insufficiency is fraught with many uncertainties: non-physiologic, poorly reproducible and thus the results may contain little useful information especially concerning response to rhGH therapy, rely on arbitrary definitions which are assay, age and puberty stage dependent and may be expensive and uncomfortable. Perhaps most importantly, they (easily) identify the child with severe GHD, but are of limited value in discriminating between normal short children and those with partial GHD. Added to this murky mix is that the role of sex hormone priming is unclear. Since sex steroids cause the increase in GH secretion and circulating IGF-I levels at puberty, one assumes that exposing prepubertal children to sex steroid priming facilitates GH release and may make retesting unnecessary or avoid mis-classification of the condition. Not all agree that sex hormone priming is required, for a concern is that of spontaneous GH release in prepubertal children, who do not have circulating endogenous sex steroids. The ‘primed’ test would then force an un-physiologic state for a prepubertal child. Certainly the lower bound of normal GH release would be higher than the ‘usual’ one. Historically, the primed test was useful when only severely children with GHD could be treated because of the inadequate supply of pituitary GH. With the present supply of rhGH available to children with idiopathic short stature, some of whom may have partial GHD, it becomes less of an issue. Perhaps a compromise would be that sex hormone priming is not required routinely but perhaps useful in the small group of peri-adolescent age children with significantly delayed puberty because children of this age ‘should’ have greater concentrations of circulating sex steroid hormones. The conundrum is not making a diagnosis of GHD, but of determining who is GH responsive. Testing itself is expensive and not always definitive. It may very well be prudent to do a clinical trial of rhGH treatment for 6 to 12 months, for it is the early growth response that predicts, perhaps best, the long term growth response to therapy with rhGH.