Approach to a child with short stature AG

Approach To A Child

With Short Stature

Moderated by Dr. Mohd. Haseeb Sir

Presented by Dr. Akshay Golwalkar

Why we need to concern?

BECAUSE…………………..

IT CAN BE A SIGN OF DISEASE,

DISABILITY

&

A SOCIAL STIGMA CAUSINGPSYCHOLOGICAL STRESS

Definition*

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 or

Excessively short for mid mid parental or target

height

Males

Age (y )

30

34

38

42

46

50

54

58

62

66

70

74

78

Hei

ght

(in)

Hei

ght

(cm

)

2 4 6 8 10 12 14 16 18 20

70

80

90

100

110

120

130

140

150

160

170

180

190

200

0

+2

+1

-1

-2

-2.0 SD (2.3 percentile)

*Essential Pediatrics, 7th Edition OP Ghai; IAP spatiality series Endocrinology 2nd edition

Approximately 3% children in any population will be short*

Approximately half will be physiological ( familial or

constitutional ) & half will be pathological short stature*

Most common cause is malnutrition in developing

countries*

Familial or constitutional is the leading cause in

developed countries*

*IAP spatiality series Endocrinology 2nd edition

Growth Physiology

Growth

Environment

HormonesGenetic factors

Dietary factors

•Growth hormone

•Thyroid hormone

•Gonadotrophins

Factors affecting height

Intra

uterine

Growth

factors

Nutrition

Thyroid harmoneGrowth Hormone

FSH

LH

GH

Thyroid

Birth 1 year 2 years 4years 8years Puberty Adult

Endocrinology of Postnatal GrowthDeficiency of thyroxin

blunts GH secretion.

GROWTH

Linear

Growth

Ponderal

Growth

Skeletal maturation

& Bone Growth

Linear Growth

Increased Growth

Velocity @ puberty

Etiology of short stature*

Physiological

– Familial

– Constitutional short stature

Pathological

– undernutrition

– Chronic systemic illness

– Hormonal deficiency states

– Psychosocial dwarfism

– SGA

– Skeletal dysplasias

– Genetic syndromes

*Essential Pediatrics, 7th Edition OP Ghai; IAP spatiality series Endocrinology 2nd edition

Familial Vs Constitutional* Feature Familial Short Stature Constitutional Short Stature

1) Sex Both equally affected More common in boys

2) Family History Of short stature Of delayed puberty

3) Height Velocity Normal Normal

4) Puberty Normal Delayed

5) Bone Age Normal Less than

chronological age

6) Final Height Short, but normal for

target

height

Normal


Approach to a child with short stature

History & “observation”

Anthropometric measurements

Plotting on growth chart

Physical examination

workup

History

Birth history

Nutritional history

Chronic disease history (asthma, CHD,

CLD,CRF, chronic diarrhea)

Drugs….chronic steroid therapy

Family 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

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

1) Accurate height measurement

Below 2 yrs*- supine length with

infantometer.

Assessment of a child with short stature


Assessment of a child with short stature

For older children-

Harpenden Stadiometer

Height measurements

Without footwear

Heels & back touching

the wall

Looking straight ahead

Growth chartTarget centiles

Increments in Height*

Age Increase in height

Birth 50cm

1st yr age 25cm

2nd yr age 10cm

3rd yr age 7.5cm

4th yr age 5cm

5th yr age 5cm/year


Growth Velocity*

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.*


At least 3 measurements with preferably 6 months

interval in between is necessary to comment on

growth pattern.*


Growth Velocity*

Growth Monitoring*

Age Ht/Length Wt Head

circumference

Others

Birth Yes Yes Yes --

1.5, 3.5

6, 9, 15 mths

Yes Yes Yes --

1.5 to 3 yrs 6 monthly 6 monthly 6 monthly Mid arm

3.5 to 5.5 yrs 6 monthly 6 monthly --

6 to 8 yrs 6 monthly 6 monthly -- BMI & SMR

9 to 18 yrs Yearly Yearly -- BMI & SMR

yearly


Target height*

Target height in cm for a girl = [(mother's height

in cm + father's height in cm) /2] - 6.5 cm

Target height in cm for a boy = [(mother's height

in cm + father's height in cm) /2] + 6.5 cm


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 the

target height

Within Target RangeNot Within Target Range

Watch GV Observe – GV Normal

Assessment of body proportion

Lower segment (LS) pubic symphysis to ground

Upper segment (US) total height/length – LS

US to LS ratio is 1.7 at birth decreases by 0.1

every year to reach 1 at 7 to 10 years of age.*


Arm span

Upper segment: Lower segment ratio

Increase :

– Achondroplasia

– Skeletal dyspalsias

– untreated hypothyroidism

Decreases :

– Short trunk (scoliosis)

– Short neck (klippel-Feil syndrome)

– Arachnodactyly (Marfan’s, homocystinuria)

Assessment of body proportion

Physical examination

Weight measurement (fat & short….endocrine,

thin & short……under nutrition or chronic illness)

Systemic examination to rule out systemic illness

skeletal system examination including spine

Dysmorphic features

Tanner staging

Clues to etiology from examination*

Examination finding Etiology

Disproportion Skeletal dysplasia, rickets, hypothyroidism

Dimorphism Congenital syndromes

Pallor Chronic anemia, chronic renal failure

Hypertension Chronic renal failure

Frontal bossing, depressed nasal bridge,

crowed teeth, small penis

Growth hormone deficiency

Goiter, coarse skin Hypothyroidism

Central obesity, striae Cushing syndrome

*Essential Pediatrics, 7th Edition OP Ghai;

Workup for short stature

Level 1* ( essential investigations):

Complete hemogram with ESR

Urinalysis

Stool

Blood

BONE AGE


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

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

TW Method - 13 Bones

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 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

Level 2*:

Serum thyroxine, TSH

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

Workup for short stature

if Level 1 investigations are normal and bone age is delayed proceeds to

level 2*


HYPOTHYROIDISM

Short, stocky child, dull looking, puffy face.

Thickened skin 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*


HYPOTHYROIDISM

CONGENITAL

(UNTREATED):

Slow growth vel.

Delayed BA

Constipation

Mental retardation

unless treated at 2-3

months.

ACQUIRED(UNTREATED)

Asymptomatic

Delayed growth

Constipation

Normal IQ if developed

after 2yrs of age

Dry skin

Ideally every neonate should be screened for

TSH levels before discharging from nursery.*

Regardless of symptoms all children with

significant short stature should be screened for

hypothyroidism.*

Rx: thyroxine according to the age appopriate

dosage

HYPOTHYROIDISM


Turners syndrome

Short stature may be the only clinical

manifestation.

Karyotyping should be considered 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

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.

Level 3*:

GH stimulation test with Clonidine or insulin & serum

insulin like GF-1 levels

Neuroimaging

Celiac serology ( anti- endomysial or anti- tissue

transglutaminase antibodies)

Duodenal biopsy

If height < -3 SD → proceeds to level 3 investigations*


GROWTH HORMONE DEFICIENCY(GHD)

Normal length & weight at birth.

Growth delay seen >1yr of age

BA < CA by at least 2 yrs

Normal intelligence & delayed BA.

Infantile gonadal development

Growth hormone actions

Growth Hormone

GH receptors

Liver

Synthesis of IGF1Metabolic effects

IGF receptors

Growth Hormone

GH receptors

GH receptors Liver

Synthesis of IGF1

Proliferation of Cells

Cellular growthLinear 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

Physical features

Cherubic face; fair complexion

Normal IQ

Frontal bossing

Midfacial crowding

Truncal obesity

Micropenis

Workup for GH def

GH deficiency is diagnosed by a low level of serum

insulinlike growth factor-1 (IGF-1) in the presence of

deficiency of 3 or more pituitary hormones*.

Patients who have deficiency of 2 or less pituitary

hormones or pituitary-hypothalamic disease with low

IGF-1 levels require stimulation tests to establish the

diagnosis of GH deficiency*.

*Hartman ML, Crowe BJ, Biller BM, Ho KK, Clemmons DR, Chipman JJ. Which patients do not require a

GH stimulation test for the diagnosis of adult GH deficiency?. J Clin Endocrinol Metab. Feb 2002;87(2):477-

85.

Workup for GH def

GH stimulation testInsulin-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.

*Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML,. Evaluation and treatment of adult growth hormone

deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. Jun 2011;96(6):1587-609

GH stimulation test

INTERPRETATION:

Peak stimulated growth hormone conc. <5.1ng/ml*

in response to GH stimulation test or

<11.1 ng/ml in response to combined Arg- GHRH

stimulation test with patients having BMI less

than 25*.

*Molitch ME, Clemmons DR, Malozowski S, Merriam GR, Vance ML,. Evaluation and treatment of adult growth hormone

deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. Jun 2011;96(6):1587-609

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

Workup for GH def


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)*IAP spatiality series Endocrinology 2nd edition

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 time

Follow up & watch for at least one year before

starting the treatment.

Earlier is always better & ideal is 3-4yrs

Never delay beyond 7-8yrs

Usually growth velocity is maximum in first year

of therapy.


Devices:

Freeze dried – commonest

Liquid prep- easy to administer

GH THERAPY

Automated pen type

G H THERAPY

Routes of administration:

S.c- currently using

Intranasal- under trials

Timing: 2-3 times/wk

Response 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.

CRITERIA FOR STOPPING Rx:*

Decision by patient that he/she is tall enough

Growth rate <1 inch/year

BA >14YRS in girls & 16yrs in boys.


FOLLOWUP:*

required as there is risk of :primary hypothyroidism /

adrenal insuffiency so periodic follow up needed.

SIDE EFFECTS:*

Pseudotumour cerebri, hyperglycemia, acute

pancreatitis, liver abnormalities, gynaecomastia,


Take Home Message

Take height properly along with the height of parents

Plot on Growth Charts and find out the target centile

Determine the growth velocity by follow up at least after 6

months

A systematic approach and simple tests like bone age

usually reduce the need & hence cost of further

investigations

For dynamic stimulation tests refer the child to specialist

centres

SHORT STATURE

Dysmorphic Normal

•Russle Silver

•Noonan’s

•Turner syndrome

•Downs syndrome

•Prader Willi

•Pseudo-

hypoparathyroidism

ProportionateDis-

Proportionate

•Constitutional

•Familial/genetic

•IUGR

•Ch Malnutrition

•Celiac Disease

•Chronic systemic

disease (CRF, CLD)

•GH Deficiency

•Hypogonadism

•Hypothyroidism

•Osteogenesis

imperfecta

•Achodroplasia

•Rickets

•Metabolic and

storage disorders

(short spine)

Level 1 ( essential investigations):

1.Complete hemogram with ESR

2.BONE AGE

3.Urinalysis ( Microscopy, pH, Osmolality)

4.Stool ( parasites, steatorrhea, occult blood)

5.Blood ( RFT, Calcium, Phosphate, alkaline phosphatase, venous gas, fasting sugar,

albumin, transaminases)

Level 2 (investigations for short stature)

1.Serum thyroxin, TSH

2.Karyotype to rule out Turner syndrome in girls

Above is normal and bone age is delayed proceeds to level 2

• If above investigations are normal and height between -2 to -3→

observe height velocity for 6-12 months

• If height < -3 SD → proceeds to level 3 investigations

Health & Medicine

Approach to a child with short stature AG