There are few issues in pediatric endocrinology which have generated as much controversy as that of GH treatment of ISS. The genesis of this debate is totally understandable, given that ISS is not a disease, but, rather, a heterogeneous collection of conditions that are defined auxologically as a height below −2 S.D., without evidence of an underlying systemic, nutritional, endocrine or chromosomal disorder. One can quite rightfully state that no matter how many children might be treated, 5% will always be below the 5th percentile. Despite this caveat, it seems unreasonable to deny therapy to a patient who may experience benefit. And yet, we continue to treat many ISS patients. Some of the justifications are listed below: 1. Treatment of short stature related to a wide variety of other non GH deficient states, such as Turner syndrome, SGA, Noonan syndrome, SHOX deficiency, and Prader Willi Syndrome, is widely approved. 2. Recognition that ISS constitutes a heterogeneous group of disorders, many of which may have demonstrable etiologies, such as unsuspected defects of SHOX, NPR2, FGFR3 and dominant negative mutations affecting the GH-IGF axis. Indeed, all short stature that is not due to environment or systemic disease will ultimately prove to have a molecular basis. As such, it becomes extremely challenging to determine where the boundary lies between pathology and normal variation. 3. Difficulties in the diagnosis of GHD, with estimates that at least 70% of children labeled and treated as GHD are actually ISS patients. 4. Heterogeneity in the growth response to GH of patients labeled as GHD and ISS, so that considerable overlap exists between these two groups of patients.
Failure to identify an agency-approved indication for GH should not necessarily exclude a patient from potential beneficial therapy. A trial of GH treatment seems reasonable in such cases.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology