Approach to child with

short stature

Name: Dr. Shreya Thapa

PGYII
Moderator: Dr. Archana Nepal
Contents
Growth
Phases of growth
Short stature
Causes of short stature
Assessment
Diagnosis
Investigation
Management
Growth
• Net increase in the size or mass of tissues
• Largely attributes to multiplication of cells and increase in the intracellular
substance
 Growth Physiology

Environment

Genetics Growth Hormones

Growth hormone
Thyroid hormone
Gonadotrophins
Dietary
 Phases of growth

Childhood Adolescent
Fetal
1. Maternal: Nutrition (most
Infantile 1. Hormonal( GH, Hormonal ( sex
thyroxine) steroids, GH)
important), obstetrics complications 1. Nutrition (PEM,
(PIH, multiple pregnancies, chronic anemia, vitamin 2. Nutrition
systemic diseases like CHF, acquired deficiency)
infections like TORCH) 2.Thyroid hormone
2. Placental: size, HPL, CRH, EGF
3. Fetal: IGF 2, insulin

PERMANENT
• Other factors in postnatal phase:
1. Genetic: Chromosomal causes, mutation in single gene
2. LBW
3. Gender: height and weight lesser in girls compared to boys
4. Infections: diarrhea, respiratory tract infections
5. Trauma: to growth plate
6. Medication: androgen
7. Social factors: Low socioeconomic level, poverty, summer, broken family and
orphanage, anxiety, insecurity, lack of emotional support, cultural factors in infant
rearing and feeding, maternal education
1. Infantile phase: Initially there is rapid linear
growth which slows down
2. Childhood phase: there is linear growth with
constant velocity
3. Adolescent phase: growth spurt occurs with
maximum height velocity
 Boys
• Onset: 12 years
• SMR stage 4 for
Girls pubic hair
• Onset: 10 years development
• SMR stage 3 for
breast
development

Q. Why boys tend to be taller?

 Growth spurt in boys occur 2 years
later compared to girls and
amplitude of spurt is greater than
girls
Short stature
• Height 2 SD (standard deviation) or more below the mean height for that gender
and chronological age in a given population OR
• Height more than 1.5 SD below the midparental height (MPH) OR
• Fall in growth velocity below the 25th percentile.

• According to NDHS 2022, prevalence of stunting is 25%

Growth failure
• H/A curve deviates downward across two major height centile curves. Eg. From
above 25th to below 10th OR
• HV as follows :
2-4 years: <5.5 cm/year
4-6 years: <5cm/year
6 years-puberty: <4cm/year for boys and <4.5 cm/year for girls
Causes
SHORT STATURE

PHYSIOLOGICAL
PATHOLOGICAL

CONSTITUITIONAL FAMILIAL PROPORTIONATE DISPROPORTIONATE

Characteristics Familial short stature Constitutional delay in growth and
puberty
Definition Low normal height velocity Childhood short stature with
relatively normal adult height

Bone age Normal Delayed but within 2 years of

chronological age
Puberty Normal Delayed
Parents puberty Usual timing Delayed
Pubertal growth rate Low normal Low
Adult height Short but within MPH target Initially looks short but later
normal
Parents stature Small Normal
 Pathological

Proportionate
Disproportionate

Dysmorphic features Dysmorphic features

present absent US>LS LS>US
Eg. Skeletal dysplasia Eg. Mucopolysaccharidoses
Spondyloepiphyseal dysplasia

Turner syndrome Malnutrition, Chronic

Down syndrome diseases, Endocrine,
Psychosocial deprivation,
Russell silver syndrome Treatment, Others
Prader Willi syndrome
Noonan syndrome
 Endocrine

Malnutrition Treatment

NO DYSMORPHISM PRESENT

Psychosocial Chronic
Deprivation diseases
Others
(Craniopharyngiom
a, bulimia nervosa,
anorexia nervosa,
SGA)
Undernutrition
• Most common cause of poor growth globally
• Deficiencies like zinc, chronic anemia and protein deficiency
• Causes: poverty, self-imposed restriction (due to fear of obesity), underlying
systemic disease that interferes with food intake or absorption or increases
energy needs
• Hallmark is low weight-for-height
• Bone age is delayed
Psychosocial deprivation

• Emotional deprivation or abusive (physical or neglect) environment.

• Characteristic feature: presence of multiple transverse metaphyseal growth arrest
lines in growing long bones, which is not seen in GHD due to other causes
Two types
Type I: <2 years, associated with unhappy home environment and neglected
entirely, child responds to proper nutrition
Type II: older child, rejected by parents eg. Eating food from garbage cans,
associated with ACTH and GH deficiency
• Hormones and growth normalizes only when relocated to better environment
Growth hormone deficiency

• Two types: Isolated or associated with other pituitary

hormone(MPHD)
C/F:
• Normal BW, length
• Doll-like facies, head round with a prominent forehead, protuberant eyes,
depressed nasal bridge and saddle-shaped nose
• Midfacial hypoplasia, delayed dentition, crowded teeth, high pitched voice
• Small hands and feet, slow growth of hair and nails
• Micropenis, hypoplastic labia
• Short, plump child, truncal obesity and normal body proportions
• Bone age delayed, low growth velocity
 Hypothyroidism
C/F
• Normal birth weight and length
• Dry skin, hoarseness, edema, lethargy, feeding problems, constipation, puffy or
coarse facies, macroglossia, umbilical hernia, large fontanels, hypotonia, dry skin,
hypothermia, prolonged jaundice
• Myalgia, paresthesia, arthralgia
• Cognitive dysfunction, intellectual disability, depression
• Fatigue, weakness, dyspnea on exertion, weight gain
• Menorrhagia, pubertal delay
• Low growth velocity and delayed bone age
Cushing syndrome
• Weight gain
• Moon facies, buffalo hump,
truncal obesity, abdominal
striae, thin skin and muscle wasting
• low growth velocity
• Bone age within normal limits
Precocious puberty

Two types:
1. Central precocious puberty, also known as gonadotropin-dependent precocious
puberty, refers to the early occurrence of normal puberty. In girls <8 years and in
boys <9 years
• Advanced bone age
• Pattern of secretion of pituitary gonadotropins and gonadal sex steroids is normal
but early.
2. Peripheral precocious puberty, also known as gonadotropin-independent
• Causes: adrenal or gonadal disorders, human chorionic gonadotropin-producing
tumors, longstanding untreated hypothyroidism, exposure to exogenous sex
steroids
• The clinical manifestations are similar to those of central precocious puberty
except that the sexual maturation may be that of the opposite sex. Eg. androgenic
effects in girls with congenital adrenal hyperplasia
Turner syndrome
• Deletion of X chromosome; XO
• Important in girls with short stature
• Virtually all girls with Turner syndrome
have short stature, with an average
adult height approximately 20 cm
shorter than predicted by the
mid-parental height
• Treatment: GH therapy
Noonan syndrome
• AD
• Also k/a male turner
• Affect both males and
females
• Several genes like
PTPN11, KRAS have
been implicated
• Ptosis, cryptorchidism,
short stature are
characteristics
• Treatment: GH therapy
Achondroplasia
• AD
• Mutation in FGF receptor-3
• US>LS
• Characteristic features:
short arms and legs,
large head, frontal bossing,
small midface, flat nasal bridge,
trident hand and spinal kyphosis
SGA
• Birth weight or length or both less than −2 SD for gestational age
• 70–90% of SGA babies catch up to their genetic potential within the first 2–4
years of life
• Approximately 10 percent fail to experience catch-up growth
Idiopathic short stature
• Diagnosis of exclusion
• The child is short, below the target range
• Normal growth velocity with normal bone age
• No evidence of genetic, systemic or endocrine disorder
• Some consensus classify FSS and CDGP under idiopathic short stature (ISS)
Steps in assessment
1. Accurate height measurement: infantometer for <2 years and stadiometer for
>2 years
2. Comparison with population norms: growth charts
Growth standards Growth references
Prescriptive define how a population of children Descriptive and describe the growth of children at that
should grow given the optimal nutrition and optimal time. They represent how children are growing rather
health than how they should be growing.

Eg. WHO 2006 growth charts for children under 5 Eg. 2007 Indian growth charts by Khadilkar, CDC 2000
years charts

Advantage: children of all countries, races, ethnicity Advantage: they are true representative
can be compared against a single standard of the existing growth pattern of children and allow us
to study the secular trend in terms of height, weight,
and obesity

Disadvantage- over diagnose underweight and Disadvantage- need to be updated at least once in a
stunting in a large number of apparently normal decade
children

Ideally prescriptive charts are preferred

< 5 years: WHO 2006
>5 years: IAP 2015
• Disease-specific growth charts: Turner syndrome, achondroplasia and
Down syndrome
• Preterm babies: Fenton charts, intergrowth 21 charts
3. Height velocity
Change in height
Change in time
Eg. 4 years/male child with height 100cm increase upto 110cm at 7
years
Height velocity is 3.3 cm/year
Normal values

2-4 years: 5.5-9 cm/year

4-6 years: 5-8.5 cm/year
6 years-puberty:
• 4-6 cm/year for boys and
• 4.5-6.5 cm/year for girls
Importance of HV
 Most sensitive in detecting growth abnormalities
 Plotting height at one point give NO idea about the direction of growth
 Diagnose chronic disease in presymptomatic stage eg. Celiac disease may only
present with short stature
4. Comparison with child’s own genetic potential: mid parental height

Girls: (father’s height-13)+mother’s height/2

Boys: (father’s height+(mother’s height +13)/2
• Plot the MPH at 18 years ( as most of the growth is complete) represents 50th
percentile for that family
• Also plot projected height by extrapolating the child's growth along the current
channel to the 18 years
• Projected height must be within +/- 8.5 cm
 Eg. 7years/ male with
height 110cm
• Father’s height: 165cm
Mother’s height: 155cm
MPH: 166.5cm

Range: 158-175 cm

If the child's bone age is

delayed or advanced, then
the projected height should
be plotted based on the
bone age rather than the
chronologic age
5. Body proportion
US/LS, arm span

Age US/LS
Birth 1.7 Age Arm span vs height
3 years 1.3 Birth 2.5 cm shorter than height
6 years 1.1 11 years Equals to height
10 years 1 Thereafter Greater than height
Adults 0.9
6. Sexual maturity rating: tanner staging
7. Bone age
• Radiograph of left hand and wrist and assessing ossification centers
• 4 method
1. Greulich-Pyle method: Simple, most commonly used but not very accurate.
Hand X-ray is compared to a set of age and gender specific radiographs in the
atlas and bone age is assigned as the age at which radiograph matches closest to
the patient's X-ray
2. Gilsanz & Ratib is similar to Greulich-Pyle where pattern matching is done
3. Tanner-Whitehouse 3 method: 20 bones are evaluated (13 short or long bones
and 7 carpals) and then given a score which is used to give a bone age. Accurate
but exhaustive
4. Bone Expert method: radiograph is uploaded in a software that gives the
estimation of bone age. Quick, accurate and removes the subjective bias but
expensive
• Delayed or advanced bone age is defined as a bone age that is 2 SD or more
below or above the mean
Delayed bone age: constitutional delay of growth and puberty (CDGP), nutritional
deficiency, underlying systemic disease (eg. inflammatory bowel disease), growth
hormone deficiency and hypothyroidism
Normal bone age: familial short stature, younger girls with Turner syndrome
Advanced bone age: precocious puberty, hyperthyroidism
 History
Domains Ask about Suggestive of
Symptoms: Appetite, abdominal pain, diarrhea, rectal Crohn’s disease, celiac
GI, respiratory,
joint problems,
bleeding disease
renal, sleep
pattern, CNS, Recurrent respiratory infections, k/c/o asthma CF, immunodeficiency
endocrine,
visual
Arthralgia, arthritis IBD, JIA, celiac disease
Lethargy, cold intolerance, constipation Hypothyroidism
Polyuria CKD, RTA
Hyperphagia, sleep apnea, snoring PWS
Headache, vomiting, visual problems Pituitary, hypothalamic
space occupying lesions
Domains Ask about S/O
Drug history Under any medications (eg. Steroids)
Antenatal IUGR, substance intake, TORCH
history
Birth LBW SGA, syndrome
history: Breech delivery, birth asphyxia GHD, Multiple pituitary
birth weight,
complications hormones deficiency
during deliver or
postnatal Neonatal jaundice Hypothyroidism, cortisol
deficiency
Edema of hands and feet in neonatal Turner syndrome
period
Neonatal hypoglycemia, jaundice, Hypopituitarism
micropenis
Nutrition Feeding difficulties PWS
history Inadequate intake Malnutrition
Domains Ask about S/O
Development Delay Noonan, down, PWS
history
Learning disabilities Turner syndrome

Poor school performance Hypothyroid

Family history Height of parents, growth disorders, endocrine FSS, skeletal dysplasia,
disorders, skeletal disorders syndrome, GHD
Consanguinity Genetic causes
Delayed puberty CDGP
Socioeconomic Social environment, broken family, anxiety, Psychosocial
history: relation insecurity, lack of emotional support deprivation
with parents,
Environment at home
Physical examination

Characteristics Suggestive of
Underweight Malnutrition, chronic disease,
malabsorption
Overweight Endocrine, syndrome
Disproportionate Skeletal dysplasia, rickets
Pallor Anemia, CKD
Cyanosis, jaundice, clubbing Chronic systemic diseases
Hypertension CKD, CAH, Cushing's syndrome
Physical examination
Characteristics Suggestive of
Webbed neck, shield chest, low posterior hairline, Turner syndrome
Cubitus valgus, genu valgum, short 4th
metacarpal, Breast development absent
Hypertelorism, downward slant of eyes, low set Noonan syndrome
ear, Webbed neck, pectus excavatum,
Hypospadias, cryptorchidism
Triangular facies, asymmetry of face, body, Russell silver syndrome
clinodactyly
Almond shaped eyes, long philtrum, obesity, Prader Willi syndrome
small hands, feet, Cryptorchidism
Characteristics
Papilledema
Visual defects, Optic atrophy
Signs of physical abuse
Suggestive of
CNS mass effect, optic
nerve hypoplasia
MPHD/Septo-optic
dysplasia
Psychosocial cause
Characteristics Suggestive of

Frontal bossing, midfacial hypoplasia, Growth hormone deficiency

immature facies, depressed nasal bridge,
central fat deposition, Small hands, feet,
Micropenis
Facial puffiness, coarse facies, goiter, Hypothyroidism
bradycardia
Suprascapular, supraclavicular fat pad, Cushing syndrome
skin atrophy, purple striae, Moon facies,
buffalo hump, obesity
Midline defects (cleft palate, single Hypothalamic-pituitary hormone
central incisor) deficiency
Characteristics Suggestive of
Bony deformities Rickets, skeletal dysplasia
Midface hypoplasia, frontal bossing Achondroplasia
Hepatosplenomegaly, signs of chronic diseases Chronic systemic diseases
like abdominal distension (celiac disease,
malabsorption), anal skin tags (Crohn's disease)
Investigations
Level 1 (essential) Level 2 Level 3
CBC, ESR, CRP TFT Celiac serology
RFT, FBS KARYOTYPING GH tests
Bone age IGF1,IGFBP-3
Urinalysis MRI brain
Stool examination for steatorrhea, Genetic tests
parasites
ABG, calcium, phosphate, PTH, ALP,
albumin and transaminases

If normal but bone age

If normal
delayed
Management
Counseling of parents and dietary advice
Monitoring of height
Treat the cause eg. GH replacement, levothyroxine, steroids, Limb
lengthening
GH therapy
GH replacement Indications:
1. Growth hormone deficiency
2. Chronic kidney disease
3. Turner syndrome
4. Small for gestational age
5. Prader Willi syndrome
6. Idiopathic short stature
7. Noonan syndrome
8. SHOX mutation (Short stature Homeobox)
 Work up for growth hormone deficiency
Random serum GH of >10mg/dl generally excludes growth hormone deficiency but
a random low value does not confirm the diagnosis
Overnight fasting pharmacologic agent is administered samples
collected
Normal response>10 mcg/L, but a cutoff of 7.5 mcg/L is often used for modern
assays
IGF-1 and IGFBP-3 together are normal then GH is also normal
 If low then it is either growth hormone deficiency or resistance
GH replacement: if epiphyses open
1. Aqueous biosynthetic recombinant human growth hormone
Dose: 0.16 and 0.24 mg/kg/week SC divided once daily. Mostly, started at the
upper end of this range (0.24 mg/kg/week, ie, approximately 35
micrograms/kg/day).
2. Others: Lonapegsomatropin, Somapacitan, Somatrogon (long acting)
Response to Treatment
• Growth velocity of >2.5cm/yr
• Maximum response in 1st year with growth velocity >95th percentile
Note: With each increasing year growth rate tends to decline. If GV falls below 25th
percentile or <2-2.5cm/yr, assess compliance before increasing the dose

Criteria for stopping the treatment

• Decision by patient that he/she is tall enough
• Growth rate <2.5cm/1inch per year
• Bone age >14years in girls and 16years in boys
Adverse drug reactions of GH therapy
• Headache
• Papilledema
• Fluid retention
• Insulin resistance
• Glucose intolerance
• Worsening of scoliosis
• Slipped capital femoral epiphysis
• Adenoid hypertrophy
• Gynecomastia
Levothyroxine
Levothyroxine PO OD
• 1 to 3 years – 4 to 6 mcg/kg
• 3 to 10 years – 3 to 5 mcg/kg
• 10 to 16 years – 2 to 4 mcg/kg
Acquired primary hypothyroidism, serum TSH and free T4 checked 6-8 weeks after
initiation of treatment OR after any dose change and then every 6 to 12 months.
Central hypothyroidism, serum free T4 or T4 is generally required for dose
monitoring (Target free T4 in the upper one-half of the reference range)
• Serum TSH, if checked, is usually low or undetectable in treated children with central
hypothyroidism, so this test generally is not useful for monitoring these patients
Course — Continue treatment until growth and pubertal development are
complete
If treated prior to puberty typically have good catch-up growth and normal adult
height outcomes
If treated just before or during puberty, and who have longstanding chronic
hypothyroidism, adult height may be diminished, deficit ranges from 8 to 14 cm
Steroids: adolescents with CDGP
 Testosterone enanthate or cypionate 50-100mg/month IM or SC for 3-6 months
 Oxandrolone 2.5 mg daily for 3-12 months
 Estrogen along with androgens
Red flag signs

 Height >2-2.5 SD below mean

 Subnormal growth velocity
 Abnormal body proportions
 Abnormal height: weight ratio
 Dysmorphic features
 Goiter
 Abnormal CNS, ophthalmologic examination
 Acquired growth failure in previously healthy growing child
SUMMARY
References
1. Edited by Paul VK, Bagga A. Ghai essential pediatrics. CBS Publishers
& Distributors Pvt Ltd; 2019.
2. Vaman Khadilgar. IAP Textbook on Pediatric Endocrinology, 2019
3. Kliegman RM, Toth H, Bordini BJ, Basel D, editors. Nelson pediatric
symptom-based diagnosis. Elsevier Health Sciences, 2nd edition.
Thank you
Drug Dose Measurement of Peak GH secretion Side effects
GH
Clonidine 5 mcg/kg 0, 30, 60 and 90 1 HR hypotension and
(stimulation of (maximum 250 minutes hypoglycemia
GHRH via alpha- mcg) PO
adrenergic
pathways)
Arginine 0.5 g/kg 0, 30, 60, 90, and 1 HR None
(maximum of 40 120 minutes
g) IV over 30
minutes
Glucagon 0.03 mg/kg 1-3 hrs 2-3 hrs nausea, vomiting,
(maximum 1 mg) sweating, or
SC headaches.
Insulin Regular insulin 0, 15, 30, 45, and 15 to 30 minutes Hypoglycemia
0.05 to 0.1 unit/kg 90 minutes
IV