• Their Prophet said to them: 'Allah has raised Saul to
be your king. ' But they replied: 'Should he be given
the kingship over us, when we are more deserving of
it than he and he has not been given abundant
wealth? ' He said: 'Allah has chosen him over you
and increased him with amplitude in knowledge and
body. Allah gives His kingship to whom He will. Allah
is the Embracer, the Knower.
• 12 year old boy healthy
• his height is far below 3ed centile
• aslo far from mid parentral height.
• No FH of constitutional delay.
• GV 4 cm/year , on exam : non dysmorphic
• bone age 1yaer delay .
• GH stimulation test normal. IGF-1, IGFBP3
• It is common condition.
• The term has been in use since at
• It is a clinical description rather than a
Idiopathic short stature
• Definition: stature that is 2 standard
deviations (SD) or more below the
mean for age (approximately the 2nd
percentile) and for whom no
endocrine, metabolic, or other
diagnosis can be made .
• Children with ISS fall into two main
• Familial short stature (in which bone age
is not delayed and the child is growing
within the parental target range)
• Constitutional delay of growth (in which
bone age is delayed)
• Also combination of these two condition.
• usually Children with ISS have
normal growth velocity
• no biochemical or other evidence for
a specific growth-retarding condition.
• normal growth hormone (GH)
responses to pharmacologic agents
• some children with ISS may have low
serum concentrations of IGF-I
• Several studies have demonstrated
that growth hormone therapy
generally increases height velocity
acutely and may increase adult
height in children with ISS.
• was approved by the United States Food
and Drug Administration (FDA) in 2003.
• The indication is for children with current
height below -2.25 SD of the mean, in
whom the epiphyses are not closed, and
whose expected adult height is less than
63 inches (160 cm) for boys and 59
inches (150 cm) for girls
• the use of growth hormone for ISS
• A majority of children with short stature
will experience some catch-up growth
during puberty without GH treatment
• There is little evidence that short stature
has a detrimental effect on an
individual's psychosocial or physical
• The available evidence suggests only
modest efficacy for GH treatment in
children and adolescents with ISS.
• treated individuals remain relatively
short compared with their peers
• The decision to treat children and adolescents
with ISS using growth hormone requires
complex psychosocial considerations
• GH treatment should be considered only if the
short stature represents a disability to the child
and is not amenable to counseling and
• GH treatment could have adverse psychosocial
consequences due to the extreme focus on a
child's stature conferred by GH treatment.
• Most patients with ISS have normal
• Growth hormone treatment at standard
doses appears to have minimal
physiological adverse effects.
• High-dose GH treatment
(71 mcg/kg/day) was reported to
accelerate the onset of puberty and
epiphyseal closure in children with ISS
but lower doses (34 or
53mcg/kg/day) did not
• For children with ISS the optimal
dosing range is well established.
• In prepubertal children with ISS, GH
routinely is used in the range of 25 to
• Higher doses lead to modest
increases in short-term growth
velocity and adult height .
For how long
• continue treatment only if the height
velocity increases by 50 percent or at
least 2.5 cm/year above the baseline
• If the initial growth response is
significant . treatment is continued until
linear growth decreases to less than 2.0
to 2.5 cm (about 1 inch)/year.
• If bone age >14 for girls, >16 for boys.
• evidence supports the idea of
adjusting GH dose based on IGF-I
levels when treating children with
• GH dosing be adjusted to maintain
IGF-I within a normal range.
• IGF-I levels approximately four weeks
after beginning therapy or changing
the GH dose, and approximately
every 6 to 12 months
thereafter, similar to the approach we
use for patients with GH deficiency
Recombinant human IGF-I
• Recombinant IGF-I (rhIGF-I) has
been effectively used for treatment of
children with "severe primary IGF-I
• A preparation of rhIGF-I is approved
by the FDA for this use.
• Patients with ISS may have degrees of
growth hormone insensitivity, with
normal or elevated circulating serum
GH levels but low levels of insulin-like
growth factor-I (IGF-I) and IGF binding
protein 3 (IGFBP-3).
• For these children, direct replacement
of IGF-I may be more effective than GH
Recombinant human IGF-I
• An alternative approach to attempt to
delay pubertal development and
• The range of the effect is limited to
approximately 0 to 4 cm.
• Boys with mild to moderate short
stature whose puberty and bone age
• treatment with testosterone during
adolescence may be helpful to
promote puberty and accelerate
• in adolescent males it will facilitate
growth by delaying epiphyseal closure.
• Preliminary studies suggest that
treatment with aromatase inhibitors, with
or without concomitant growth hormone,
increases predicted adult height.
• long-term safety and efficacy results are
• In girls, aromatase inhibitors would be
expected to slow growth because they
inhibit estrogen production.
• Treatment of children with idiopathic short
stature (ISS) with growth hormone is
• the decision to treat children with ISS
using growth hormone depends on
• Growth hormone treatment is likely to yield
only modest gains in height compared with