EVALUATION AND

MANAGEMENT OF SHORT
STATURE
DEFINITION

● Height 2 standard deviation (SD) or more below the mean height for that
gender and chronological age (CA) in a given population.
● Height >1.5 SD below the midparental height (MPH).
● Fall in growth velocity below the 25th percentile.
STATS - PREVALENCE OF SHORT STATURE IN INDIA

● Within the age group of 5–8 years, short stature was reported at 3.7%
● 7.3% in the age group of 13–16 years, while in children in the age group
of 9–12 years, 8% (135/1684) of short stature was found, which was the
most significant proportion
● Males have more short stature than females in this age group of 9–12
years because males attain late peak height velocity as compared to
female
NORMAL GROWTH

● By definition, approximately 2.3% to 3% of children have short stature.

● By the age of 2 years, the height percentile of a healthy child usually
stabilizes and correlates with parental heights
● Growth velocity varies with age, sex, and race
● After the first 2 years of life, until puberty, the average growth rate for
boys and girls is 6.25 cm per year with a range of 4 to 7.5 cm per year.
NORMAL GROWTH VELOCITY BY AGE
MEASUREMENTS OF GROWTH

● During measurements of growth, the child should stand erect, with the
back of the head, back, buttocks, and heels touching a firm vertical
structure such as the vertical bar of a stadiometer, with shoes off and
interfering hair accessories removed.
● A child younger than 2 years of age should be measured on a firm
horizontal platform that contains an attached yardstick, a fixed headboard,
and a movable footplate
● The growth charts that have been widely used are those published by the
Centers for Disease Control and Prevention’s National Center for Health
Statistics (CDC/NCHS) as well as those published by the World Health
Organization (WHO)
CLINICAL EVALUATION

● Careful historical reviews and systematic physical examinations are

keystones to the evaluation process.
● In most cases, a diagnosis can be made with relative certainty from the
history and physical examination alone.
● Familiarity with the growing process and the physiology of growth, as
well as the clinical features of many diseases and syndromes associated
with short stature, is definitely an asset, and in some cases a spot
diagnosis can be made.
CLINICAL EVALUATION
CLINICAL EVALUATION
CLINICAL EVALUATION
CLINICAL EVALUATION
CLINICAL EVALUATION
CLINICAL EVALUATION

● Careful and precise measurement of height, weight, arm span (distance

between tips of the middle fingers with the arms raised and stretched to a
horizontal position) and upper/lower segment ratio is the most useful
exercise in the physical examination.
● The lower body segment can be determined by measuring the distance
from the symphysis pubis to the floor with the child standing erect against
a wall.
● The upper body segment value can be obtained by subtracting the lower
body segment value from the child’s height.
● The upper-to-lower body segment ratio is then derived by dividing the
upper body segment value by the lower segment value.
CLINICAL EVALUATION

● Children with achondroplasia, hypochondroplasia, rickets, multiple

epiphyseal dysplasia, osteogenesis imperfecta, chondrodysplasia punctata,
metaphyseal chondrodysplasia, thanatophoric dwarfism, Ellis Van
Creveld syndrome, or long-standing hypothyroidism have relatively short
extremities and therefore a higher upper/lower segment ratio.
● On the other hand, children with spondylodysplasia,
mucopolysaccharidosis, severe scoliosis, hemivertebrae, or metatropic
dwarfism have a lower upper/lower segment ratio
● Children with simple obesity are usually tall for age.
CLINICAL EVALUATION
● The recording of vital signs is also important in the evaluation.
● Hypothermia and bradycardia may be signs of hypothyroidism.
● Abnormal blood pressure may be a clue to cardiovascular disease.
● An appraisal of the child’s general health and nutrition status is also very
important.
● The stage of sexual development should also be recorded.
● A thorough physical examination should be performed targeting features of
chronic illnesses and dysmorphic syndromes (Table).
● Chromosomal disorders usually manifest as a multiplicity of congenital
abnormalities.
● Familiarity with the dysmorphic features may allow a spot diagnosis to be
made.
CLINICAL EVALUATION
CLINICAL EVALUATION
FORMULAS FOR CALCULATING MID PARENTAL HEIGHT IN
CHILDREN
 SUGGESTED LABORATORY TESTS FOR
CHILDREN WITH SHORT OR TALL STATURE
INVESTIGATIONS
RADIOLOGICAL INVESTIGATIONS
LABORATORY EVALUATION
● Investigation should be guided by history and physical examination
findings.
● Indiscriminate testing should be avoided.
● The following laboratory tests may be useful in the evaluation of a child
with short stature and a deficient growth rate: complete blood cell count with
differential (anemia, infection, parasitic disease, malignancy); erythrocyte
sedimentation rate or C-reactive protein level (infection, inflammatory
bowel disease, collagen vascular disease, malignancy); urinalysis (urinary
tract infection, renal disease)
LABORATORY EVALUATION
● Stool examination for occult blood (inflammatory bowel disease,
malignancy); serum calcium, phosphorus, and alkaline phosphatase (rickets,
hypophosphatasia); serum thyrotropin, free thyroxine (hypothyroidism);
serum insulin like growth factor 1 (IGF-1), and bone age assessment.
● Bone age determination not only is useful in the differential diagnosis of the
various causes of short stature but also may be used to estimate the probable
adult height of an individual.
● The most commonly used method to assess bone age is the use of the
Greulich and Pyle atlas
LABORATORY EVALUATION
● Screening for mutations of the short stature homeobox gene (SHOX) should
be reserved for short children with any combinations of the following
physical findings: increased sitting height/height ratio, decreased arm
span/height ratio, short or bowed forearm, above-average body mass index,
muscular hypertrophy, Madelung deformity, cubitus valgus, and dislocation
of the ulna at the elbow
● If growth hormone (GH) deficiency is suspected, high-quality contrast-
enhanced magnetic resonance imaging of the hypothalamus and pituitary
gland is an excellent modality for early diagnosis of a lesion in the central
nervous system such as a craniopharyngioma
LABORATORY EVALUATION
● Screening tests for the secretion of GH include post exercise or sleep
sampling; a serum GH level of greater than 10 ng/mL by immunoradiometric
assay rules out GH deficiency
● g. Measurement of serum IGF-1 and IGF-binding protein 3 (IGFBP-3)
should be considered in the evaluation of the GH insulin like growth factor
axis
● Serum IGFBP-3 concentration has greater specificity than serum IGF1
concentration in the diagnosis of GH deficiency
ETIOLOGY
ETIOLOGY
Constitutional Growth Delay

● Constitutional growth delay is the most common cause of short stature.

● Characteristically, children with constitutional growth delay are of normal
length and weight at birth, but during the first few years of life their growth
velocity slows down.
● By the time they enter school, their height and weight measurements
decrease to near or below the third percentile on the standard growth curves.
● This is followed by growth at a low-normal rate, paralleling a lower
percentile curve throughout the prepubertal years.
ETIOLOGY
Constitutional Growth Delay

● The bone age usually is retarded but, in contrast to patients with

hypothyroidism and hypopituitarism, not as retarded as the height age.
● Onset of puberty is delayed: puberty develops when the bone age reaches
about 10½ years in girls and 11 to 11½ years in boys.
● Growth continues until the epiphyses fuse.
● Normally, this occurs around the age of 18 years in boys and 15 years in
girls.
● As such, catch-up growth may continue into the early 20s in males and late
teens in girls.
● There is often a family history of “late bloomers” in one or both parents
ETIOLOGY
Familial Short Stature

● Familial (racial or genetic) short stature, the second most common cause of
short stature, may occur as a genetically determined family trait based on
polygenic inheritance of genes associated with growth.
● At times, familial short stature may result from IGF-1 receptor gene
mutations.
● It is important that parental height be considered when evaluating children
with familial short stature, since their ultimate height is related to the mid-
parental height.
ETIOLOGY
Familial Short Stature

● The mid-parental height can be calculated by averaging the parents’ heights

after first adding 13 cm to the mother’s height if the subject is a boy, or
subtracting 13 cm from the father’s height if the subject is a girl.
● Extrapolation of the child’s anticipated growth along his or her channel
should yield an adult height within plus or minus 5 cm of the derived mid-
parental height.
● If the child’s bone age is advanced or delayed, then the projected height
should be plotted based on the bone age rather than the chronological age
● The ultimate adult height is often below the tenth percentile and usually
within the range predicted by mid-parental height
ETIOLOGY
Intrauterine Growth Retardation

● Etiopathogenetically, both endogenous (ie, chromosomal and genetic)

factors and exogenous factors (eg, maternal illnesses, maternal drug and
alcohol abuse, placental insufficiency) must be considered.
● In all of these disorders, there is probably a defect in cellular proliferation,
and these children are small for age.
● Children who have catch-up growth usually do it in the first 2 years of life.
● Catch-up growth may be delayed in children who are born prematurely.
Approximately 10% to 15% of affected children do not have catch-up
growth and have persistent short stature. Puberty is not delayed and bone age
is normal in children affected by intrauterine growth retardation
ETIOLOGY
Other causes also include:

● GH Deficiency
● Hypothyroidism
● Cushing Syndrome
● Androgen Excess
● Chromosomal and Genetic Disorders
● Psychosocial Dwarfism
● Chronic Malnutrition
● Chronic Systemic Diseases
● Skeletal Dysplasias
● Idiopathic Short Stature
DIFFERENTIAL DIAGNOSIS OF SHORT STATURE
DIFFERENTIAL DIAGNOSIS OF SHORT STATURE
COMPLICATIONS
● Children with short stature may experience bullying, teasing, victimization,
exclusion, and juvenilization.
● Affected children may have low self-esteem. Parents may have concerns and
anxiety.
● The psychosocial stress on the children and parents cannot be
overemphasized.
● The condition may have an adverse effect on the quality of life of the child
and parents.
● Short stature may be a harbinger of an occult underlying chronic disorder.
MANAGEMENT
MANAGEMENT
● Treatment depends on the nature of the underlying disorder.
● When the cause is treatable, it is important to initiate treatment as early as
possible to optimize the final adult height potential.
● Most children with constitutional growth delay and familial short stature do
not require treatment apart from watchful observation.
● If the cause does not require treatment or is untreatable, a frank and thorough
explanation for the short stature should be given to the child and the family.
● Affected children should be encouraged to discuss the implications of the
diagnosis so to minimize the psychological disturbances.
● Psychological stress should not be overlooked, and psychological counseling
may occasionally be necessary.
MANAGEMENT
● The treatment of GH deficiency or bio inactive GH (Kowarski syndrome) is
GH replacement therapy, usually in the form of recombinant DNA-derived
human GH (rhGH) given subcutaneously.
● Somatropin, an rhGH produced by recombinant DNA technology in
Escherichia coli, has been widely used since 1985.
● The recommended dose ranges from 20 to 40 µg/kg once daily based on
serial measures of serum IGF-1 levels
● In 2003, the Food and Drug Administration (FDA) approved the use of GH
for children with idiopathic short stature with a height more than 2.25
standard deviations (1.2nd percentile) below the mean, in whom the
epiphyses are not closed, and whose predicted adult height without
therapeutic intervention is less than 160 cm for males and less than 150 cm
for females
MANAGEMENT
● In spite of FDA approval, the decision about whether to use GH for such
purposes should be made on a case-by-case basis after a thorough discussion
with the family and the child.
● The physical and psychosocial burdens as a result of short stature and the
efficacy, potential adverse effects, and cost of the treatment should be taken
into consideration.
● The recommended dose ranges from 43 to 67 µg/kg once-daily by
subcutaneous injection.
● These doses are substantially higher than those recommended for children
with GH deficiency, presumably because children with idiopathic short
stature have relatively impaired sensitivity to GH.
MANAGEMENT
● Daily administration of GH is superior to less frequent administration.
● Treatment with GH is continued if the height velocity increases by at least
2.5 cm per year above the baseline height velocity when reassessed after 1
year of treatment or until the child grows to a height considered satisfactory
to the family and clinician.
● Although GH therapy does improve final height in patients with idiopathic
short stature, treated individuals remain relatively short when compared with
peers of normal stature.
● In general, GH therapy at standard doses has an acceptable safety profile.
● Adverse events are rare and include diabetes mellitus, benign intracranial
hypertension, increased intraocular pressure, scoliosis, arthralgias, slipped
capital femoral epiphysis, etc.
MANAGEMENT
● Adolescent boys with constitutional growth delay and puberty and moderate
short stature (taller than -2.5 standard deviations) are more appropriately
treated with low-dose testosterone rather than GH.
● Testosterone can be given intramuscularly, orally, or topically (ie, patches or
gels).
● Oxandrolone, a testosterone derivative with fewer androgenic effects than
testosterone and which does not aromatize, is the treatment of choice.
● Aromatase inhibitors such as anastrozole and letrozole may also be used for
such purposes.
● Available data suggest that aromatase inhibitors may improve short-term
growth outcome, but final adult height data are scarce
MANAGEMENT
● In adolescent girls with constitutional growth delay and puberty and
moderate short stature, a short course of estrogen therapy may be
considered.
● The use of aromatase inhibitors is not a treatment option, because aromatase
inhibitors would slow growth by inhibiting estrogen production
● Children with severe short stature from GH insensitivity due to genetic
defects in the GH receptor (eg, Laron syndrome) or postreceptor
mechanisms or from the development of GH-inactivating antibodies may
benefit from IGF-1 therapy.
● Mecasermin, a recombinant human IGF-1 can be used in this regard. The
main concern with recombinant human IGF-1 therapy is the increased risk of
hypoglycemia
 INDICATIONS FOR REFERRAL TO A PEDIATRIC
ENDOCRINOLOGIST IN CHILDREN WITH SHORT STATURE
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