Controversies in the Definition and Treatment of Idiopathic Short Stature (ISS)

The term idiopathic short stature (ISS) refers to short children with no identifiable disorder of the growth hormone (GH)/insulin like growth factor (IGF) axis and no other endocrine, genetic or organ system disorder.This heterogeneous group of short children without GH deficiency (GHD) includes children with constitutional delay of growth and puberty, familial short stature, or both, as well as those with subtle cartilage and bone dysplasias.In rare cases, ISS is due to IGF molecular abnormalities.In this review we tackle the major challenges in the definition and treatment of ISS. Conflict of interest: None declared DEFINITIONA heterogeneous population Idiopathic short stature (ISS) is defined as a condition characterized by a height more than 2 standard deviations below the corresponding average height for a given age, sex and population, without findings of disease.(1,2, 3) According to this definition, it is estimated that approximately 80% of all children referred for short stature, at the end of the diagnostic work-up, will be labeled as ISS.(4)The concept behind this definition is that ISS can be considered as part of the continuum extending from complete growth hormone deficiency (GHD) to normality and covering different degrees of GH secretion and responsiveness.To better define this population, ISS has recently been subdivided into two major groups: a) familial short stature (FSS), when the child is short compared with the reference population, but remains within the range of target height; b) non-familial short stature (NFSS), when the child is short both in comparison with the reference population and the target height.This latter subgroup inevitably includes short children with constitutional delay of growth and puberty (CDGP).(1)The need of a sub-categorization stems from the classical distinction between the "normal variants" of growth (namely FSS and CDGP), characterized by the achievement of an adult height within the range of target height, and the "real" ISS children, whose growth pattern and natural history are different from FSS and CDGP and are thought to have a different etiology. More about the distinction between ISS and normal variants of growthClassically, FSS children present with stature within the target height range, no bone age delay and normal growth rate