SHORT STATUREINDICATION OF GROWTH HORMONE THERAPY

PRESENTED BY:DR.NUPURMODERATOR-DR.MANISH

Who is the short child?Short stature is defined as height that is two standard deviations below the mean height for age and sex (less than the third percentile).

Ormore than two standard deviations below the mid-parental height.

OrGrowth velocity less than 25th percentile on a velocity curve over a period of 6-12 months

Short stature is a common problem and should be early detected and managed.

Boys who are short are more likely to come to medical attention than girls who are short. a higher percentage of the girls had underlyingpathology that requires intervention

SHORT STATURE VS F.T.T

• SHORT STATURE should not be confused with failure to thrive. • FAILURE TO THRIVE is associated with greater

impairment in weight gain than linear growth (resulting in a reduced weight-for-height ratio).

• Although failure to thrive may be associated with short stature or slow growth velocity, it primarily represents an inability to gain weight appropriately and only secondarily an impairment in linear growth

STEPS TO EVALUATE History and physical examination.

World Health Organization <5 years, and IAP >5yrs

Midparental height and growth velocity should be calculated to evaluate a child's growth vs. potential height.

Bone age

CLINICAL HISTORY

EXAMINATION

Body Proportions• Lower segment (LS): Measure from the symphysis

pubis to the floor. • Upper segment (US): Subtract the LS from the height.

• U/L birth = 1.7• U/L 3years = 1.3• U/L > 7 years = 1

• Proportionate (ie, involves both the trunk and the lower extremities) or

• Disproportionate (ie, involves one more than the other).

• Disproportionate (ie, involves one more than the other).• U/L > Increase ratio ---------- short lower limb.• (e.g. Achondroplasia, Skeletal dysplasia)• U/L < Decrease ratio :• Short trunk (Scoliosis, MPS) • Short neck (Turner Syndrome).

MID PARENTERAL HEIGHT AND PROJECTED HEIGHT

PROJECTED HEIGHT• Projecting the current growth curve to

adulthood in children with normal bone age, or by using a bone age atlas in those with delayed bone age.

• Most children will have a projected adult height within 10 cm (4 in), or two standard deviations, of their MPH

• A projected height that differs from the MPHby more than 10 cm suggests a possible pathologic condition

GROWTH VELOCITY

• Growth velocity is a measurement of growth rate.

• Children with normal variants of height tend to have a normal growth velocity (5 cm [2 in] per year for children between five years of age and puberty) after catch-up or catch-down growth

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

BONE AGE

Method of assessing skeletal maturity observed directly by visualization of epiphyseal growth plates on X-ray.

X-rays useful to determine skeletal age –

1. <1 year: shoulder x-ray2. 1-13 years: hands and wrists3. >13 years: elbow and hip

Bone age is necessary:

in the diagnosis of FSS and CGD; for interpreting hormone levels in pubertal age; for diagnosis of precocious puberty or hyperandrogenism; for deciding whether to treat or not the above mentioned

conditions; for predicting adult height in normal children; in evaluating any child with growth and/or puberty disorders; in deciding the time to start replacement therapy in

hypogonadism; in monitoring children on growth hormone therapy.

Methods for bone age evaluation

1. Greulich & Pyle method - In their method for each of these bones an elaborate description of its developmental stages is included.

2. Tanner and Whitehouse method - It is based on a set of bone’s standard maturity for each age population.

3. Roche–Wainer–Thissen – The five predictor variables in the RWT method are recumbent length, weight, bone age, chronological age, and parental heights.

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

TW Method - 13 Bones

Delayed bone age• Constitutional short

stature• Hypothyroidism• Celiac disease• GH deficiency

Advanced bone age

• Precocious puberty or CAH

• premature adrenarche• overgrowth syndromes,

Sotos syndrome, Beckwith-Wiedemann syndrome and Marshall-Smith syndrome

familial short stature or idiopathic short stature :BA=CA

constitutional delay of growth and puberty or endocrine disorders :BA<CA

calculating bone age every 12 months might be useful to differentiate constitutional delay of growth from endocrine diseases.

Children with endocrine disorders, such as growth hormone deficiency, hypothyroidism, or glucocorticoid excess: have normal to increased weight

children with systemic disease : have decreased height and weight

Short Stature

1) Prenatal Causes: i) Intra-uterine

Growth Restriction

ii) Intra-uterine Infections

iii) Genetic Disorders (Chromosomal & Metabolic Disorders)

Proportionate Short Stature

Normal Variants

* Familial short stature* Constitutional Delay

Pathological

Disproportionate Short Stature

2) Postnatal Causes: i) Undernutritionii) Chronic Systemic Illness-CVD: CHD,.-RSD: Asthma.- Renal: RTA, CRF.- GI T: Malabsorption. - Chronic Severe Infections-Hematological:Thalassemia.-iii) Psychosocial Short Stature .iv ) Endocrine Causes:-Growth Hormone Deficiency.-Hypothyroidism

1- With Short Limbs: Achondroplasia

2- With Short Trunk: Mucopolysaccharidsis

DIFFERENTIAL DIAGNOSIS

STEPWISE INVESTIGATIVE WORK - UP• Level-1 investigations – 1. CBC2. CRP & ESR3. Urinalysis4. Stool examination5. S. Electrolytes6. Liver and Renal function tests7. Bone age

• Level-2 investigations – 1. Thyroid function tests2. Karyotyping3. Prolactin4. Neuroimaging

• Level-3 investigations – 1. Coeliac serology &

duodenal biopsy2. GH stimulation test &

serum IGF-1 levels

Provocative tests (GH stimulation tests)

Random sampling of serum GH is insufficient to diagnose GH deficiency; GH stimulation tests are required

A limited number of provocative agents should be used after an overnight fast in a well standardized protocol.

Insulin tolerance test (ITT)Glucagon test (100 microgrammes/kg BW IM(max.1 mg)L-dopa testArginine test(0.5g/kg BW , slow IV infusion (max,30g) ,Clonidine test (0.1- 0.15 mg/kg BW orally).

Provocative tests•In healthy volunteers peak GH levels are 10 ng/ml (20 mU/ml).

•If peak GH level of 10 ng/ml (20 mU/ml) is detected , it exclude classical GHD

•In a classical GHD case a GH peak is not detected or GH peak is less than 3 ng/ml (6 mU/ml) in all these tests.

•In partial GHD cases GH peak of 8-10 ng/ml (16-20 mU/ml) may be seen.

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

• The combination of IGF-1 and IGFBP-3 measurements appears superior to determining either analyte alone in the diagnosis of growth hormone (GH) related disorders

GROWTH HORMONE

Growth hormone actionsGrowth 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

BIOMARKERS OF GH ACTION

FDA has approved 8 indications(Growth hormone therapy):

1. Noonan syndrome.2. GH deficiency3. Turner syndrome4. chronic renalfailure before transplantation,5. idiopathic short stature6. small-for-gestational age 7. Prader-Willi syndrome8. SHOX gene abnormality,

GH TREATMENT

Take Home Message Take height by proper method and plot it on appropriate growth

chart. Use Growth Charts appropriately. Every child must have proper growth monitoring so as to know

whether the child is on his proper road to growth. Any child with short stature is not always familial and should

evaluated completely.