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shortstature.ppt
1. Dr . Sumera Akram
SR Pediatrics
SHORT STATURE IN
CHILDREN
2. Definition of short stature
Height below 3rd centile or less than 2 standard
deviations below the median height for that age
& sex according to the population standard
OR
Even if the height is within the normal
percentiles but growth velocity is consistently
below 25th percentile over 6-12 months of
observation
The term ‘Dwarfism’ is no longer used for
short stature.
Essential Pediatrics, 7th Edition, OP Ghai; Fima Lifschitz- Pediatric Endocrinology
3. What is normal linear growth?
age Height in centimeter Height in inches
At birth 50 20
At 1 year 75 30
2-12 yr [ age(yr)x7] +77 [age(yr)x2.5]+30
4. Short stature in Pakistan
A Pakistani study stated that the prevalence of
short stature was 16.5% among children who
are aged from 6 to12 years
8. Growth hormone/somatotropin
191 amino acid single-chain polypeptide
anterior pituitary of the brain in the acidophilic, somatotrophic cells.
Regulation: complex feedback mechanisms in response to stress, exercise, nutrition, sleep, growth
hormone-releasing hormone (GHRH) produced in the hypothalamus, somatostatin (-)-produced in
various tissues throughout the body, and ghrelin-produced in the gastrointestinal tract.as part of the
hunger response.
pulsatile release.
in general, HGH levels will be increased in childhood, spike to their highest levels during puberty, and
subsequently decrease with increased age.
HGH has two mechanisms of effect:
A) direct effects of HGH on the body are through its action on binding to target cells to stimulate a
response.
B)The indirect effects occur primarily by the action of insulin-like growth factor-1, which hepatocytes
primarily secrete in response to elevated HGH binding to surface receptors.
Once activated, the Janus activating tyrosine kinases (JAKs) 1 and 2 will bind to the latent cytoplasmic
transcriptions factors STAT1, STAT3, and STAT5, and be transported into the nucleus inducing increased
gene transcription and metabolism to produce insulin-like growth factor-1 for release into the circulation.
Insulin-like growth factor-1 then has an impact on the growth and metabolism of peripheral tissues. One
can think of the effects of HGH as a combined effect of both HGH and insulin-like growth factor-1.
9. Effects of growth hormone:
Promotes growth :
HGH induces growth in nearly every tissue and organ in the body. However, it is most notorious
for its growth-promoting effect on cartilage and bone, especially in the adolescent years.
Chondrocytes and osteoblasts receive signals to increase replication and thus allow for growth
in size via HGH’s activation of the mitogen-activated protein (MAP) kinases designated ERKs
(extracellular signal-regulated kinases) 1 and 2 cellular signaling pathways. Activation of this
phosphorylation intracellular signaling cascade results in a cascade of protein activation, which
leads to increased gene transcription of the affected cells and ultimately causes increased
gene replication and cellular growth.
Insulin-like growth factor-1 binds to its receptor, IGF-1R, on the cellular surface and activates a
tyrosine kinase-mediated intracellular signaling pathway that phosphorylates various proteins
intracellularly leading to increased metabolism, anabolism, and cellular replication and
division. Furthermore, it acts to inhibit apoptosis of the cell, thus prolonging the lifespan of
existing cells. The net result is to encourage the growth of tissue and to create a hyperglycemic
environment in the body.
Metabolic Effects
HGH impacts metabolism primarily by up-regulating the production of insulin-like growth factor-1
and its subsequent effect on peripheral cells. The intracellular signaling activation that occurs,
as stated above, also has a significant impact on the basal metabolic functions of organ tissues.
In general, cells enter an anabolic protein state with increased amino acid uptake, protein
synthesis, and decreased catabolism of proteins. Fats are processed and consumed by
stimulating triglyceride breakdown and oxidation in adipocytes. Additionally, HGH suppresses
14. Familial vs constitutional short stature
Feature Familial Short Stature Constitutional Short Stature
1) Sex Both equally affected More common in boys
2) Length at Birth Normal Normal (starts falling <5th
centile in 1st 3yrs of life)
3) Family History Of short stature Of delayed puberty
4) Parents Stature Short (one or both) Average
5) Height Velocity Normal Normal
6) Puberty Normal Delayed
7) Bone Age & Chronological
Age
BA = CA > Height Age CA > BA = Height Age
8) Final Height Short, but normal for target
height
Normal
16. Intra-uterine Growth Restriction
Arrest of fetal growth in early embryonic life causes
reduction in total number of cells, leading to diminished
growth potential in postnatal life
BW <10th centile for gestational age
Most of these babies show catch-up growth by 2yrs of age,
but 20-30% may remain short
Subtle defects in the GH-IGF axis are considered to be
responsible
Growth Velocity is normal
• BA = CA
• Learning disabilities could be present
17. Genetic Syndromes:
A) Chromosomal Disorders
- Turner syndrome ( XO) :
an incidence of 1 in 2000
live births
- should be ruled out even
if typical phenotypic
features are absent
- Other e.g.: Down, Noonan, Prader-Willi,
Silver- Russel, Seckle syndrome
B) Inborn Errors of Metabolism
-eg. Galactosemia, Aminoaciduria
20. Under nutrition:
One of the commonest cause of short stature
Protein Energy Malnutrition, anemia and trace element
deficiency such as Zinc def are common causes
Weight gain is slow and muscles are wasted. Long standing
malnutrition leads to Stunting (Stunting is short, but short is not
necessarily stunting. Stunting is a condition of failure to thrive due to
malnutrition in the first thousand days of a child's life. Stunting is growth
retardation that is not limited to short height but also includes social and
environmental inadequacies that cannot be reversed by providing adequate
nutrition alone (Leroy et al., 2019).
BA < CA
Diagnosis: good dietary history, anthropometric measurements
25. Hypopituitarism
• Genetic
• congenital syndrome
• acquired form
Multiple pituitary
hormone
deficiency:
• Genetic
• acquired
Isolated growth
hormone
deficiency:
• at the level of receptors
• post receptor insentivity
Growth
hormone
insensitivity:
26. 1) Multiple pituitary hormone deficiency:
1 in 4000-1in 10000 live births
Mutation in 7 candidate genes( PROP1, SOX2-3
etc)
Septo-optic dysplasias
(holoprosencephaly,anencephaly)
Acquired pituitary hypoplasia:trauma, infections,
tumours,resection,radiation etc.
All pituitary hormone deficincies
Hypopituitarism
27. 2)Isolated Human growth hormone deficiency:
due to disruption of GH axis
Genetic
acquired(radiotherapy for malignancy,
meningitis, histiocytosis, trauma)
- Normal length & weight at birth
- Growth delay seen >1yr of age,
growth velocity < 4cm/year
- BA < CA by at least 2 yrs
-neonatal emergencies,prolong neonatal cholestatic jaund
Infantile gonadal ice,nystagmus,micropenis, small mid face
Normal intelligence.
Hypopituitarism
28. 3) Growth hormone insensitivity (Laron’s Syndrome)
- Metabolic disorder, AR inheritence,
Laron syndrome is characterized by clinical features of growth hormone (GH)
deficiency and biochemical findings suggestive of GH resistance.
GH levels are typically normal or elevated; levels of insulin-like growth factor-1
and its binding proteins are typically very low.
Hypopituitarism
29. - Short, stocky child; dull looking, puffy face
- Thickened skin & subcutaneous tissue
with myxematous appearance, cold
intolerance
- - Protuberant abdomen with umbilical
hernia
- - Infantile sexual development & delayed
puberty
- - Bone age markedly delayed
- - Diagnosis- Low T4 levels, high TSH
levels
Hypothyroidism
30. Growth retardation(early feature) he secretion of adrenal androgens may
lead to an acceleration of bone age and eventually compromise
growth potential
Other features:
Obesity, plethoric moon facies,
abdominal striae, hypertension,
decreased glucose tolerance
Gonadal disorders:
- Adiposogenital dystrophy ( Frohlich syndrome)
moderate growth retardation, bone age normal
or slightly delayed
- Precocious puberty: early fusion of epiphyseal
centres
Cushing syndrome:
32. Skeletal dysplasias:
Aka chondrodysplasias
Inborn error in formation of
components of skeletal system
causing disturbance of cartilage
& bone
Abnormal skeletal proportions
& severe short stature
Diagnosis-
family history, measurement of
body proportions, examination of limbs & skulls, skeletal survey
35. Clues to etiology from history
History Etiology
History of delay of puberty in parents Constitutional delay of growth
Low Birth Weight SGA
Neonatal hypoglycemia, jaundice,
micropenis
GH deficiency
Dietary intake Under nutrition
Headache, vomiting, visual problem Pituitary/ hypothalamic SOL
Lethargy, constipation, weight gain Hypothyroidism
Polyuria CRF, RTA
Social history Psychosocial dwarfism
Diarrhea, greasy stools Malabsorption
37. Clues to etiology from examination
Examination finding Etiology
Disproportion Skeletal dysplasia, rickets, hypothyroidism
Dysmorphism Congenital syndromes
Hypertension CRF
Goitre, coarse skin Hypothyroidism
Central obesity, striae Cushing syndrome
38. Assessment of a child with short-stature
1) Accurate height measurement
Below 2 yrs- supine length with
infantometer
For older children- Stadiometer
39. 2) Body proportion estimation:
a) Upper segment: Lower segment ratio
(US:LS)
At birth: U/L is about 1.7:1 (trunk longer
than legs.)
U/L then decreases by 0.1 for every year of
age until 10 years of age when it
becomes 1:1 (trunk=legs).
After 10 years, the ratio is <1.3.
high in rickets, Turner, achondroplasia,
hypothyroidism
low in spondyloepiphyseal dysplasia,
vertebral anomalies, Marfan Syndrome
Assessment of a child with short stature
40. b) Arm span and height
At birth, AS is less than length by about 2.5 cm
By 10 years of age, AS is equal to height;
after 10 years in boys and 12 years in girls, AS
exceeds height by up to 5 cm.
If AS is greater than 5 cm, pathologic causes of tall
stature such as Marfan's Syndrome or hypogonadism
should be considered.
Assessment of a child with short stature
41. 3) Assessment of height velocity
Rate of increase in height over a period of time,
expressed as cm/year
If low – pathological cause of short stature
4) Comparison with population norms
Height plotted on appropriate growth charts &
expressed as centile or SD score
Assessment of a child with short stature
42. 5) Comparison with child’s own genetic potential
Mid parental height for boys
= mother's height + father's height /2 + 6.5cm
Mid parental height for girls
= mother's height + father's height /2 – 6.5cm
6) Sexual maturity rating ( SMR):
Also known as Tanners stages
Used in older children
Total 5 stages included in each gender
Assessment of a child with short stature
43. Stage 1
• Preadolescent
Stage 2
• Scanty, long, slightly pigmented, primarily at base of penis
Stage 3
• Darker, coarser, starts to curl, small amount
Stage 4
• Coarse, curly; resembles adult type but covers smaller area
Stage 5
• Adult quantity and distribution, spread to medial surface of thighs
Tanner staging of male:
SMR PUBIC HAIR
44. Stage 1
Preadolescent
Preadolescent
Stage 2
Slight or no
Beginning of
enlargement
Enlargement of testes and scrotum; scrotal skin
reddened, texture altered
Stage 3 Longer Further enlargement of testis and scrotum
Stage 4
Larger in
breadth,
Testes & scrotum nearly adult glans penis
develops
Stage 5 Adult Adult
Tanner staging of male
SMR Penile length Testicular size
45. Stage
1
• Preadolescent
Stage
2
• Sparse, slightly pigmented, straight, at medial border of labia
Stage
3
• Darker, beginning to curl, increased amount
Stage
4
• Coarse, curly, abundant, but amount less than in adult
Stage
5
• Adult feminine triangle, spread to medial surface of thighs
Tanner staging of female
SMR Pubic hair development
46. Stage 1
• Preadolescent; elevation of papilla only
Stage 2
• Breast and papilla elevated as small mound; areola diameter increased
Stage 3
• Breast and areola enlarged with no separation of their contours
Stage 4
• Projection of areola and papilla to form secondary mound above the level of the
breast
Stage 5
• Mature; projection of papilla only, areola has recessed to the general contour of the
breast
Tanner JM. 1962. Growth at Adolescence (2nd ed.). Oxford, England: Blackwell Scientific Publications.
Tanner staging of female
SMR Breast development
48. What is CA-BA-HA ?
Chronological age (CA) which is
calculated using the date of birth of
an individual
Bone age (BA) is an indicator of the
skeletal and biological maturity of an
individual.
Height age (HA) the age that
corresponds to the child's height
when plotted at the 50th percentile
on a growth chart
49. BONE AGE ( BA ):
Bone age assessment should be done in all
children with short stature
Appearance of various epiphyseal centers &
fusion of epiphyses with metaphyses tells about
the skeletal maturity of the child
Conventionally read from Xray of hand & wrist
using Gruelich-Pyle atlas or Tanner-
Whitehouse method
Bone age gives an idea as to what proportion of
adult height has been achieved by the child &
what is remaining potential for height gain
BA is delayed compared to chronological age in
almost all causes of short stature
Exceptions: Familial short stature,
Precocious puberty
56. Level 2:
Serum thyroxine, TSH
Celiac serology ( anti- endomysial or anti- tissue
transglutaminase antibodies)
Karyotype to rule out Turner syndrome in girls
If above investigations are normal and height between -2 to -3
SD Observe height velocity for 6-12 months
If height < 3SD level 3 investigations
Investigation:
57. Level 3:
Duodenal biopsy
GH stimulation test with Clonidine or insulin & serum insulin like GF-1
levels
Due to the pulsatile nature of HGH levels found in the blood, conventional
measurements of serum HGH are almost useless because the values may vary from
undetectable to extremely high depending on environmental stressors and
conditions. If a clinician suspects HGH deficiency, it is best to evaluate insulin-like
growth factor I and insulin-like growth factor binding protein-3 levels and to perform
HGH stimulation tests.
In an HGH stimulation test, the patient fasts overnight, and a pharmacological challenge
is added in the morning with either L-dopa,
clonidine, propranolol, glucagon, arginine, or insulin-induced hypoglycemia. HGH
serum levels are then evaluated hourly for a response to increased hormone levels.
Failure of this test to increase HGH levels, therefore, indicates HGH deficiency.
hGH>10ng/ml excludes hGH deficiency
Investigation:
59. GH s/c injectionsweek , recombinant GH,(stop
when tall enough,growth rate of <1inchyr,bone
age >14 yr in girl and >16 yr in boys)
Indication: GH deficiency, Turner syndrome,
SGA, CRF prior to transplan, prader willi
syndrome, noonan syndrome, SHOX
abnormality, idiopathic short stature)
Side effects: Incresed risk of type 2
diabetes,pseudo tumour cerebri, slipped capital
femoral epipyhsis, gynecomatia, coarsening of
features and worsening of scoliosis, creutzfeldt-
Management:
60. Monitoring with regular & accurate recording of
height is mandatory for a good outcome in any
form of therapy
Management: