Disorders of Growth Hormone in Childhood

The diagnosis of growth hormone deficiency is made by combining information from auxology, biochemistry and neuroimaging. GH signal transduction is not induced by GHR dimerisation but by a conformational change in the predimerised GHR leading to repositioning of the BOX1 motifs. In addition to GH defieincy and Laron syndrome there are now additional disorders of the GH-IGF-I axis – Stat5b deficiency, ALS deficiency, haploinsufficiency and mutations in IGF1R and mutations in the IGF-I gene. There is an expanding number of genes where mutations lead to a disturbance of pituitary gland formation and pituitary hormone deficiency, however in the majority of patients with congenital hypopituitarism the genetic aetiology remains unknown. Consider genetic screening in patients where there are multiple affected individuals in the family and in children where they have associated eye abnormalities. Response to growth hormone therapy is generally very good in patients with congenital GH defieincy where a final adult height within parental target range should be expected. In contrast in patients with radiation induced GH defiency, GH treatment is less effective and acts mainly to prevent further height loss. Recombinant human IGF-I is available for treating children with GH insensitivity. While first year height velocity often improves significantly the long term effects on height are less effective than in children with congential GH defiency treated with growth hormone. GH excess is an extremely rare disorder in childhood. All childhood patients with a GH secreting adenoma should be screened for mutations in AIP and MEN1 and management should be shared with an adult endocrinologist. Consult our FREE web-book WWW.ENDOTEXT.ORG for complete coverage on this and related topics.