Endocrine Abstracts

The investigation of growth failure can be fraught with difficulties at all ages, but never more so than in the peri-pubertal period. The differential diagnosis at this period of life includes constitutional delay of growth and puberty (CDGP), hypogonadotrophic hypogonadism (HH), GH insufficiency (GHD/GHI) and a physiological peri-pubertal reduction in growth velocity in addition to other organic causes of growth failure. Careful auxology and pubertal staging with assessment of growth velocity over a period of at least 6–12 months is usually required before making a decision to investigate a child. A decision is made to investigate a child if the height is more than 2 S.D.s below the mean, or if the child is more than 1.4 S.D.s below the mid-parental height, in conjunction with a poor growth velocity. The NICE guidelines recommend the performance of at least two tests of GH secretion, once other causes of growth failure have been excluded. Physiological tests lack reproducibility and are poorly validated; hence provocative testing remains the most widely used and accepted method of diagnosing GHD. A large number of provocative tests are available for use, and there is little or no consensus as to the most reliable tests. Lack of reproducibility, lack of normative data leading to the use of arbitrary ‘cut-off’ values, GH assay variability, and possible hazardous complications add to the controversy surrounding the tests and their interpretation. Obesity is associated with a reduction in GH secretion, often resulting in false positive results. Additionally, there is no consensus with respect to the use of sex steroid priming. The use of the GH-dependent growth factors IGF1 and IGFBP3 in isolation lacks sensitivity and specificity, but in combination with provocative tests of GH secretion, can be associated with acceptable sensitivity and specificity. More recently, the use of MRI to visualise the hypothalamo-pituitary axis has helped as an adjunct to the diagnosis of GHD; the presence of an ectopic posterior pituitary is highly predictive of GHD. The use of the GnRH test in combination with HCG stimulation may help in confirming a diagnosis of HH in isolation or combined with GHD. Finally, recent advances in molecular genetics may help in clarifying the diagnosis, with the identification of a number of genes implicated in the aetiology of GHD or HH. To conclude, the assessment of growth failure in the peri-pubertal period is associated with considerable diagnostic uncertainty, and likely requires a combination of GH provocation, measurement of IGF1 and IGFBP3 concentrations, neuroimaging and molecular genetics in order to achieve an acceptable sensitivity and specificity.