Evaluation for suspected growth hormone insensitivity in a child

GH: growth hormone; IGF-1: insulin-like growth factor 1; IGFBP-3: insulin-like growth factor-binding protein 3; GHBP: growth hormone-binding protein.
* Refer to UpToDate topic reviews on the diagnostic approach to short stature and diagnosis of GH deficiency in children.
¶ Trials of GH or IGF-1 should be performed only if the epiphyses are open. An adequate growth response is an increase in height velocity by at least 2.5 cm/year. Children whose epiphyses are nearly closed may not achieve this degree of growth response, even if they have GH deficiency or insensitivity.
Δ In a patient with suspected GH insensitivity, the possibility of Laron syndrome can be assessed by molecular testing for pathogenic homozygous or compound heterozygous mutations in the GH receptor gene. Laron syndrome is the most common form of severe GH insensitivity. Alternatively, the possibility of GH insensivity can be supported by measuring basal GH levels and GHBP or performing an IGF-1 generation test (IGF-1 response to a brief trial of recombinant GH). The results of the IGF-1 generation test are not always useful, because the protocols for performing this test have not been standardized and the levels of IGF-1 achieved are quite variable.
◊ In patients with clinical characteristics of severe GH insensitivity and a normal or elevated circulating GH level, a low level of GHBP strongly supports a diagnosis of Laron syndrome, but normal levels are uninformative. This is because patients with Laron syndrome have low GHBP levels only if the GH receptor mutation affects the extracellular binding domain, whereas GHBP levels are normal or high if the GH receptor mutation affects the transmembrane or cytoplasmic domain of the GH receptor.
§ Adequate growth response to GH confirms GH deficiency. If the growth response is inadequate, consider the possibility of an IGF-1 receptor mutation.