approach to a child with short stature dr.v.v.ratnakar reddy dr m mallikarjuna

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 -2.0 SD ( 2.3 percentile ) Generally accepted definition of normal range

Height below 3 rd 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 25 th 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, 7 th 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 Nutrition Thyroid harmone Growth Hormone FSH LH GH Thyroid Birth1 year2 years4years8yearsPuberty Adult

S HORT S TATURE Dysmorphic Normal Russle Silver Noonans Turner syndrome Downs syndrome Prader Willi Pseudo- hypoparathyroidism Russle Silver Noonans Turner syndrome Downs syndrome Prader Willi Pseudo- hypoparathyroidism 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 Osteogenesis imperfecta Achodroplasia Rickets Metabolic and storage disorders (short spine) Osteogenesis imperfecta Achodroplasia Rickets Metabolic and storage disorders (short spine)

Short Child That Looks Normal Normal growth velocityLow growth velocity Low birth weight Growth delay Idiopathic SS Chronic systemic disease Endocrine disorder Genetic, chromosomal Psychosocial Calculate TH Within Target Range Not 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

FeatureFamilial Short StatureConstitutional Short Stature 1) SexBoth equally affectedMore common in boys 2) Length at BirthNormal( crosses percentile downwards by 3yrs) Normal (starts falling Height AgeCA > BA = Height Age 8) Final HeightShort, but normal for target height 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 child Seckle 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 -

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 3 rd 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 3 rd 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

HistoryEtiology History of delay of puberty in parentsConstitutional delay of growth Low Birth Weight SGA Neonatal hypoglycemia, jaundice, micropenis GH deficiency Dietary intakeUnder nutrition Headache, vomiting, visual problemPituitary/ hypothalamic SOL Lethargy, constipation, weight gainHypothyroidism Polyuria CRF, RTA Social historyPsychosocial dwarfism Diarrhea, greasy stoolsMalabsorption Clues to etiology from history

PointerEtiology Midline defects, micropenis, Frontal bossing, depressed nasal bridge, crowded teeth, GH deficiency RicketsRenal failure, RTA, malabsorption PallorRenal failure, malabsorption, nutritional anemia MalnutritionPEM, malabsorption, celiac disease, cystic fibrosis ObesityHypothyroidism, Cushing syndrome, Prader Willi syndrome Metacarpal shorteningTurner syndrome, pseudohypoparathyroidism Cardiac murmurCongenital heart disease, Turner syndrome Mental retardationHypothyroidism, 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 findingEtiology DisproportionSkeletal dysplasia, rickets, hypothyroidism DysmorphismCongenital syndromes Infantile appearance, micropenisGhd, Mphd HypertensionCRF Short metacarpalsParathyroid dis, Turners, SXOX gene defect Goitre, coarse skinHypothyroidism Central obesity, striaeCushing 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 measurement Infanto meter: Child should be relaxed Head should be placed against an inflexible board. Legs fully extended Feet 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

GENITALS IN MALE STAGETESTI VOLPENILE LENGTH SCROTUMAGE 120 ML15 CMADULT14+

Males: SMRPubic Hair Stage 1Preadolescent Stage 2Scanty, long, slightly pigmented, primarily at base of penis Stage 3Darker, coarser, starts to curl, small amount Stage 4Coarse, curly; resembles adult type but covers smaller area Stage 5Adult 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.

SMRBreasts Stage 1Preadolescent; elevation of papilla only Stage 2Breast and papilla elevated as small mound; areola diameter increased Stage 3Breast and areola enlarged with no separation of their contours Stage 4Projection of areola and papilla to form secondary mound above the level of the breast Stage 5Mature; 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 Patients 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 SMR Predictor 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 Cells Cellular growth Linear Growth Metabolic effects IGF receptors Growth Hormone GH receptors Liver Synthesis of IGF1 Proliferation of Cells Cellular 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.

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

G H THERAPY Routes of administration: S.c- currently using Intranasal- under trials Timing: 2-3 times/wk Response to Rx: Max response in 1 st year with growth velocity >95 th percentile With each increasing year the growth rate tends to decline. If falls

Concurrent treatment with GH & LHRH with a hope to interrupt puberty CRITERIA FOR STOPPING r Rx: Decision by patient that he/she is tall enough Growth rate 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.

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 !!

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approach to a child with short stature dr.v.v.ratnakar reddy dr m mallikarjuna

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