approach to short stature

APPROACH TO A CHILD WITH SHORT STATURE

DR.V.V.RATNAKAR REDDY dr m mallikarjuna

Why we need to concern?

• BECAUSE…………………..IT CAN BE A SIGN OF DISEASE, DISABILITY, & A SOCIAL STIGMA CAUSING

PSYCHOLOGICAL STRESS

Definition

A child whose height is below 2 standard deviations for age and gender

Males

Age (y)

30

34

38

42

46

50

54

58

62

66

70

74

78

Heig

ht (in)

Heig

ht (c

m)

2 4 6 8 10 12 14 16 18 2070

80

90

100

110

120

130

140

150

160

170

180

190

200

0

+2

+1

-1

-2 -2.0 SD (2.3 percentile)

Generally accepted definition of normal range

• 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• It should not be confused with FTT as it is associated

with greater impairment in wt.gain than linear growth resulting in decresd W/H.& THE LINEAR GROWTH affected is almost always SECONDARY.

• IIIIIIIII

Definition:

Essential Pediatrics, 7th Edition, OP Ghai; Fima Lifschitz- Pediatric Endocrinology

Growth Physiology

Growth

Environment

HormonesGenetic factors

Dietary factors

•Growth hormone

•Thyroid hormone

•Gonadotrophins

Factors affecting height

Intra uterine Growth factors

NutritionThyroid harmone

Growth Hormone

FSHLHGH

Thyroid

Birth 1 year 2 years 4years 8years Puberty Adult

Growth factors at various stages

• PRENATAL GROWTH:Uterine function & size, maternal nutrition,

insulin,IGF/BP• POSTNATAL GROWTH:GH& THYROXINERapid linear growth velocity initially that

declines progressively after birth to 3 yrs.25cms 12.5cms->8cm/yr.

• 3YEARS TO PUBETY:GH& THYROID HORMONEConstant linear growth @4-7cm/yr.• PUBERTY:Sex steroids(estrogen&testosterone) in concert

with GH,THYROID,&NUTRTION Acceleration of growth pubertal growth spurt.

- Spontaneous growth hormone elevation in response to sex steroids.

• First sign of puberty in females preceeds the first sign of puberty in males by 6months.

• Pubertal growth spurt in females is 2 years earlier than males but the peak height velocity is slower in females than males(8.3cm/yr <9.5cm/yr) resulting in on an average of 13cm difference in between them.

SKELETAL MATURATION• Growth usually results from increased length

of bones coupled with rate of skeletal maturation.

• BONE AGE RADIOGRAPHY:Assessing skeletal maturation by examining the

epiphyseal maturation at hand&wrist.In <18 months- hemiskeleton x ray due to

immature hand &wrist growth plates.• Delayed bone age –indicates short stature is

partially reversible coz linear growth continues until epiphyseal fusion completes.

Normal height pattern

• Birth length 50cm• One year 75 cm• Two yrs 87.5 cm• Three yrs 93.75 cm growth • 4 yrs 100 cm velocity• 8 yrs 125 cm 6 cm • 12 yrs 150 cm per year

NORMAL GROWTH• The most critical factor in evaluating the growth

is determining GROWTH VELOCITY.• Observation of childs height pattern in the form

of “CROSSING PERCENTILE LINES” on a linear growth curve is the simplest method of observing abnormal growth velocity.

• Atleast 3 measurements with preferably 6 months intervel in between is necessary to comment on growth pattern.

• A short child with non delayed bone age is of much more concern.

SHORT STATURESHORT STATURE

DysmorphicDysmorphic NormalNormal

•Russle Silver•Noonan’s•Turner syndrome•Downs syndrome•Prader Willi•Pseudo-hypoparathyroidism

•Russle Silver•Noonan’s•Turner syndrome•Downs syndrome•Prader Willi•Pseudo-hypoparathyroidism

ProportionateProportionate Dis-Proportionate

Dis-Proportionate

•Constitutional•Familial/genetic•IUGR•Ch Malnutrition•Celiac Disease•Chronic systemic disease (CRF, CLD)•GH Deficiency•Hypogonadism•Hypothyroidism

•Constitutional•Familial/genetic•IUGR•Ch Malnutrition•Celiac Disease•Chronic systemic disease (CRF, CLD)•GH Deficiency•Hypogonadism•Hypothyroidism

•Osteogenesisimperfecta•Achodroplasia•Rickets•Metabolic and storage disorders(short spine)

•Osteogenesisimperfecta•Achodroplasia•Rickets•Metabolic and storage disorders(short spine)

Short Child That Looks Normal

Normal growth velocity Low growth velocity

Low birth weight

Growth delay

Idiopathic SS

Chronic systemic disease

Endocrine disorder

Genetic, chromosomal

Psychosocial

Calculate TH

Within Target RangeNot Within Target Range

Watch GV Observe – GV Normal

A) Proportionate Short Stature 1) Normal Variants: i) Familial ii) Constitutional Growth Delay 2) Prenatal Causes: i) Intra-uterine Growth Restriction- Placental causes, Infections, Teratogens ii) Intra-uterine Infections iii) Genetic Disorders (Chromosomal & Metabolic Disorders)

Causes Of Short Stature:

iii) Psychosocial Short Stature (emotional deprivation)

iv) Endocrine Causes: (With increased W/H) - Growth Hormone Deficiency/ insensitivity - Hypothyroidism - Juvenile Diabetes Mellitus - Cushing Syndrome - Pseudohypoparathyroidism

B) Disproportionate Short Stature 1) With Short Limbs: - Achondroplasia, Hypochondroplasia, Chondrodysplasia punctata, Chondroectodermal Dysplasia, Diastrophic dysplasia, Metaphyseal Chondrodysplasia - Deformities due to Osteogenesis Imperfecta, Refractory Rickets

2) With Short Trunk: - Spondyloepiphyseal dysplasia, Mucolipidosis, Mucopolysaccharidosis - Caries Spine, Hemivertebrae

Feature Familial Short Stature Constitutional Short Stature

1) Sex Both equally affected More common in boys

2) Length at Birth Normal( crosses percentile downwards by 3yrs)

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 but gains >4cm/yr 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 targetheight

Normal due to normal growth in pre pubertal years.

Comparison

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 Eg: Noonan,-looks like turners but both sexes are afectd.Silver- Russel – with iugr childSeckle syndrome- bird headed dwarfism.B) Inborn Errors of Metabolism -eg. Galactosemia, Aminoaciduria

Genetic Syndromes:

• 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 GA.• Most of these babies show catch-up growth by 2yrs

of age, but 20-30% may remain short.• AETIOLOGY: Subtle defects in the GH-IGF axis• Growth Velocity- normal • BA = CA • Learning disabilities could be present

Intra-uterine Growth Restriction

• One of the commonest cause of short stature in India.• Aetiology: PEM, Anemia & trace element deficiency

such as Zinc , calcium def are common causes.• Child usually appear STUNTED, with POOR Wt. gain,

Wasted muscles. • BA < CA.: • Usually child achieves catch up growth with

restoration of nutrition & may be dwarf if undernutrition is profound.

• Diagnosis: good dietary history, anthropometric measurements

Under nutrition:

1) Chronic Infections -eg:TB, Malaria, Leishmaniasis, Chr. pyelonephiritis - Growth retardation is due to impaired appetite, decreased food intake, increased catabolism, poor utilization of food, vomiting & diarrhoea2) Malabsorbtion Syndromes - eg: chronic recurrent infective diarrhoea, lactose intolerance, cystic fibrosis, celiac disease, giardiasis, cow’s milk allergy, abeta lipoproteinemia

IBD&COELIAC DISEASE- manifest with growth delay even before onset of GI symptoms.

Chronic Systemic Illness:

3) Birth defects: CHD, urinary tract & nervous system anomalies

4) Miscellaneous:(EVIDENCED CLINICALLY) Cirrhosis of liver, bronchiectasis, acquired heart diseases, cardiomyopathies, SDH

RTA& Nephrogenic DI- may present from birth with FTT.

2) Laron’s Syndrome - Metabolic disorder, AR inheritence - Clinically resembles hGH deficiency, but blood hGH levels are high - Somatomedin levels are low

3) Type 1 Diabetes Mellitus - significant growth retardation - insulin has chondrotropic effect

4) Hypothyroidism - Short, stocky child; dull looking, puffy face - Thickened skin & sct giving myxomatous appearance, cold intolerance - Protuberant abdomen with umbilical hernia - Infantile sexual development & delayed puberty - Bone age markedly delayed Diagnosis- Low T4 levels, high TSH levels

5) Cushing syndrome: Growth retardation ( early feature)• Other features: Obesity, plethoric moon facies, abdominal striae , hypertension, decreased glucose tolerance 6) Gonadal disorders: - Adiposo genital dystrophy ( Frohlich syndrome) moderate growth retardation, bone age normal or slightly delayed - Precocious puberty: early fusion of epiphyseal centres

• emotional deprivation dwarfism, maternal deprivation dwarfism, hyperphagic short stature

• Functional hypopituitarism - low IGF-1 levels & inadequate response to GH stimulation

• Type1- below 2 yrs, failure to thrive, no GH deficiency.• Type2- in > 3 yrs ,due to emotional deprivation.• Slow GV, delayd BA, resume normal growth if stimulus

is removed• Other behavioural disorders: enuresis, encorpresis,

sleep & appetite disturbances, crying spasms, tantrums• Dental eruptions & sexual development delayed

Psychosocial short stature:

• 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

Skeletal dysplasias:

• Detailed history• Careful examination• Laboratory evaluation

Diagnosis

The child is short and short for the family – what next?

• Is the child very much below the 3rd percentile or just below?

• If just below and within Target range then watch growth velocity for 6 months to one year

• If very much below the 3rd percentile and target range - investigate

Now Look At the Proportions

• Is the Child Disproportionate ?• Take sitting height and standing height• Calculate Subischeal leg length• Use proportion charts or tables• Short legs – Skeletal Dysplasia• Short spine – Metabolic and storage disorders

and rare skeletal dysplasia

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

Clues to etiology from history

Pointer Etiology

Midline defects, micropenis, Frontal bossing, depressed nasal bridge, crowded teeth,

GH deficiency

Rickets Renal failure, RTA, malabsorption

Pallor Renal failure, malabsorption, nutritional anemia

Malnutrition PEM, malabsorption, celiac disease, cystic fibrosis

Obesity Hypothyroidism, Cushing syndrome, Prader Willi syndrome

Metacarpal shortening Turner syndrome, pseudohypoparathyroidism

Cardiac murmur Congenital heart disease, Turner syndrome

Mental retardation Hypothyroidism, Down/ Turner syndrome, pseudohypoparathyroidism

Pointers to etiology of short stature

Physical examination

• Weight measurement -W/A >H/A i.e. fat & short- Endocrine. -H/A> W/A but both are below the chronological

age with thin & short- Under nutrition / chronic illness.

• Systemic examination to rule out systemic illness• skeletal system examination including spine• Dysmorphic features• Tanner staging

Examination finding Etiology

Disproportion Skeletal dysplasia, rickets, hypothyroidism

Dysmorphism Congenital syndromes

Infantile appearance, micropenis Ghd, Mphd Hypertension CRF

Short metacarpals Parathyroid dis, Turners, SXOX gene defectGoitre, coarse skin Hypothyroidism

Central obesity, striae Cushing syndrome

Clues to etiology from examination

1) Accurate height measurement• Below 2 yrs- supine length with infantometer.

• For older children- harpenden Stadiometer

Assessment of a child with short stature

Height meaurement

• Infanto meter:Child should be relaxedHead should be placed against an inflexible

board.Legs fully extendedFeet placed perpendicular onto movable flat

board.

Height measurements

• Without footwear• Heels & back touching

the wall• Looking straight ahead

in frankfurt plane. • Gentle but firm

pressure upwards applied to the mastoids from underneath

• Record to last 0.1cm

• SITTING HEIGHT:• It is the CRL in <2yrs of age• Measured upto ischial tuberosity.• Using sitting height stadiometer.• At birth:70%• At 3yrs: 57%• Adults:50%

• SUB ISCHIAL LEG LENGTH:• Height-sitting height.• USEFUL IN MEASURING THE upper to lower body

praportions.

2) Assessment of body proportion Upper segment: Lower segment ratio Increase: rickets, achondroplasia, untreated hypothyroidism Decrease: spondyloepiphyseal dysplasia, vertebral anomalies

Comparison of arm span with height

3) 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

• usually the projected height is +/- 8cm or 2 S.D. 4) Sexual maturity rating ( SMR):• Also known as Tanners stages• Used in older children• Total 5 stages included in each gender

Always Perform Sexual Maturity Rating

GENITALS IN MALESTAGE TESTI VOL PENILE LENGTH SCROTUM AGE

1 <1.5ML ≤ 3CM - ≤ 9 YRS

2 1.6-6 ML ≤ 3CM THIN RED ENLARGED

9-12 YRS

3 6-12 ML 6 CM ENLARGES FURTHER

11-12.5 YRS

4 12-20 ML 10CM ENLARGE DARK 12.5-14 YRS

5 >20 ML 15 CM ADULT 14+

Males: SMR Pubic Hair• 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 thighs surface of thighs

SMR Females pubic hair• 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.

SMR Breasts• 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

Level 1 ( essential investigations):• Complete hemogram with ESR, hepatic& renal

profile- to r/o chronic disease.• BONE AGE (x ray of left wrist)• Urinalysis ( Microscopy, pH, Osmolality)• Stool ( parasites, steatorrhea, occult blood)• Blood ( Calcium, Phosphate, alkaline phosphatase,

venous gas, fasting sugar, albumin, transaminases) • karyotyping & pelvic u/s .

Investigation:

• 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 2 investigations

• 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 ( BA ):

What does bone age tell you?

• Skeletal maturity• Correlates closely with SMR• Speaks for remaining growth potential• Helps in adult height prediction• Bone age delay of more than 2 SD i.e. about

2 years is significant

Methods of bone age assessment

• Tanner White House• • Greulich and Pyle

• No of carpals – 2

G & P Method

Patient’s film is compared with the standard of the same sex and nearest age

It is next compared with adjacent standard, both older and younger to get the closest match

Bone age

Better correlate with SMRPredictor of future height

TW Method - 13 Bones

• 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

Delayed bone age

• Constitutional short stature• Hypothyroidism• Celiac disease• GH deficiency

Familial Vs Constitutional

• hallmarks of familial (genetic) short stature is normal bone age, normal growth velocity, and predicted adult height appropriate to the familial pattern

• By contrast, constitutional growth delay is characterized by delayed bone age and predicted adult height appropriate to the familial pattern

• Patients with constitutional growth delay typically have a first or second-degree relative with constitutional growth delay (menarche older than 15 y, adult height attained in male relatives when older than 18 y)

Investigations Level 2

• IGF-I • IGF Binding protein 3• Growth hormone and other dynamic

stimulation tests• Neuroimaging• These tests are best left for the specialised

units

Level 3:• Celiac serology ( anti- endomysial or anti- tissue

transglutaminase antibodies) • Duodenal biopsy• GH stimulation test with Clonidine or insulin &

serum insulin like GF-1 levels

Growth hormone actions

Growth Hormone

GH receptors

Liver

Synthesis of IGF1

Proliferation of CellsCellular growth

Linear Growth

Metabolic effects

IGF receptors

Growth Hormone

GH receptors

GH receptors Liver

Synthesis of IGF1

Proliferation of CellsCellular growth

Linear growth

Metabolic effects(Anabolic)

IGF receptors

GROWTH HORMONE DEFICIENCY(GHD)

• CONGENITAL:-Perinatal asphyxia,-CNS malformations(septo optic dysplasia)

• ACQUIRED-idiopathic-tumors( craniopharyngioma,

glioma, germinoma)-trauma/surgery-cns infection/irradiation

- Normal length & weight at birth - Growth delay seen >1yr of age, growth velocity < 4cm/year - BA < CA by at least 2 yrs - Infantile gonadal development, - short stature &short growth vel. - Normal intelligence &delayd BA.- Diagnosis: hGH levels in sleep & after provocation with clonidine, insulin, propranolol - hGH>10ng/ml excludes hGH deficiency

Growth hormone deficiency

Workup for GH def

• endogenous GH is secreted in a pulsatile fashion. These intermittent peaks are greatest after exercise, meals, and during deep sleep. Therefore, measuring a single random serum GH value is of no use in the evaluation of the short child.

• random serum GH value of more than 10 mg/dL generally excludes GHD, a random low serum GH concentration does not confirm the diagnosis

GH stimulation test• Insulin-induced hypoglycemia is the most

powerful stimulus for GH secretion; however, this test also carries the greatest potential for harm.

• Alternate GH stimulants: Arginine, levodopa, Propranolol with glucagon, Exercise, Clonidine, Epinephrine.

• INTERPRETATION:Peak stimulated growth hormone conc. <10ng/ml

in response to 2 GH stim .test or <18ng/ml in response to combined Arg- GHRH

stim test.

IGF-1 and IFGBP-3 measurement

• IGFBP-3 and IGF-1 serum levels represent a stable and integrated measurement of GH production and tissue effects

• IGF-1 have superior diagnostic sensitivity and specificity compared with IGFBP 3.

• The combination of IGF-1 and IGFBP-3 measurements is superior when compared to individual tests

Interpretation of results

• If IGF-1 and IGBP-3 level are normal then it shows that GH level is also normal (no need for GH testing)

• If IGF-1 and IGBP-3 level are low then it may be due to GH def or GH resistance-----go for GH basal level and after stimulation

• If GH also low then GH def, if normal or high then GH resistance ( Primary IGF-1 def)

growth hormone therapy

• Currently approved as per FDA IN:• GHD• TURNERS SYNDROME• RENAL INSUFFIENCY• PRADER WILLE SYNDROME• NORMAL CHILDREN WITH HEIGHT <2.4 SD• SGA who have not reached 5th centile by 2yrs.• Shox (short stature homeobox gene)deficiency.

GH THERAPY

DOSE: 0.1U/KG/DAY s.c. at night timeFollow up & watch for atleat one year before starting

the treatment.Earlier is always better&ideal is 3-4yrsNever delay beyond 7-8yrsUsually growth velocity is maximum in first year of

therapy.Devices:Freeze dried – commonestLiquid prep- easy to administer

Automated pen type

G H THERAPY

Routes of administration:• S.c- currently using• Intranasal- under trials• Timing: 2-3 times/wkResponse to Rx:• Max response in 1st year with growth velocity >95th

percentile• With each increasing year the growth rate tends to decline.• If falls <25th percentile: assess compliance before

increasing dose.

• Concurrent treatment with GH & LHRH with a hope to interrupt puberty

• CRITERIA FOR STOPPING r Rx:Decision by patient that he/she is tall enoughGrowth rate <1 inch/yearBA >14YRS in girls & 16yrs in boys.• FOLLOWUP: required as there is risk of :primary hypo

thyroidism/adrenal insuffiency so periodic follow up needed.

• SIDE EFFECTS:Pseudotumour cerebri, hyperglycemia, acute

pancreatitis, liver abnormalities, gynaecomastia,

HYPOTHYROIDISM

• CONGENITAL (UNTREATED):

Slow growth vel. Delayd BA Constipation Mentally delayd unless

treated at 2-3 mnths.

• ACQUIRED(UNTREATED)

Asymptomatic Delayed growth Constipation Normal IQif developed

>2yrs of age Dry skin

• Regardless of symptoms all children with significant short stature should be screened for hypothyroidism.

• Rx: thyroxine usually started at 100 micro grams to be started.

Turners syndrome

• Short stautre may be the only clinical manifestation.• Karyotyping should be considred in a short female

child with pubertal delay.• SHOX gene which is required for the normal growth

is present only in a half a dose in these children• C/F: Delayed BA Normal appearance r with

Webbed neck Short metacarpals Shield shaped chest Hyperconvex finger n toe nails Cubitus valgus with wide carrying angle of arms Gonadal dysgenesis with incomplete or absent

puberty No pubertal growth spurt.

• Counselling of parents ( for physiological causes)• Dietary advice ( Undernutrition, Celiac disease, RTA )• Limb lengthening procedures ( skeletal dysplasias )• Levothyroxine ( In Hypothyroidism)• GH s/c injections ( GH deficiency, Turner syndrome,

SGA, CRF prior to transplant)

management

Thank You !!

Genghis Khan

Voltaire Pablo Picasso