Download - Short stature Dr Olcay Evliyaoğlu. Definition Height lower than 3 % in growth charts(

Short statureShort stature

Dr Olcay EvliyaoğluDr Olcay Evliyaoğlu

Definition Definition

Height lower than 3 % in growth charts(<-Height lower than 3 % in growth charts(<-2sd)2sd)

Severe short stature: Height lower than Severe short stature: Height lower than 1% (< -3sd)1% (< -3sd)

Etiologic classification of short Etiologic classification of short staturestature

Normal Normal – Constitutional growth retardationConstitutional growth retardation– Familial short statureFamilial short stature– Both Both


PathologicPathologic– Nutritional Nutritional

MalnutritionMalnutrition

MalabsorptionMalabsorption

Celiac diseaseCeliac disease

Zinc deficiencyZinc deficiency

Enflamatuary bowel diseaseEnflamatuary bowel disease


İntrauterine growth retardationİntrauterine growth retardation– SporadicSporadic– Dysmorphic syndromeDysmorphic syndrome– Chromosomal abnormalities ( Silver-Russel, Chromosomal abnormalities ( Silver-Russel,

Down, Seckel etc)Down, Seckel etc)

Skeletal dysplasiasSkeletal dysplasiasMetabolic diseaseMetabolic disease– MucopolysaccharidosisMucopolysaccharidosis– Other storage diseaseOther storage disease


Chronic diseasesChronic diseases– Chr renal diseaseChr renal disease– Chr liver diseaseChr liver disease– Congenital heart diseaseCongenital heart disease– Pulmonary diseases ( cystic fibrosis, Pulmonary diseases ( cystic fibrosis,

branchial asthma)branchial asthma)– Chr infectionsChr infections

Psychosocial dwarfismPsychosocial dwarfism


Drugs Drugs – Glucocorticoids Glucocorticoids – Estradiol ve androgensEstradiol ve androgens

Endocrine short statureEndocrine short stature– HypothyroidismHypothyroidism– GH deficiencyGH deficiency– HypopituitarismHypopituitarism– Excess cortisolExcess cortisol– PseudohypoparathyroidismPseudohypoparathyroidism


Dysmorphic syndromes with short statureDysmorphic syndromes with short stature– TurnerTurner– NoonanNoonan– Aarskog Aarskog

Disproportional short statureDisproportional short stature– Skeletal dysplasiasSkeletal dysplasias– Congenital abnormalitiesCongenital abnormalities

İdiopathic normal variant short İdiopathic normal variant short stature (familial short stature)stature (familial short stature)

Genetics determineGenetics determine

Target height is shortTarget height is short

Bone age is not delayed, and is Bone age is not delayed, and is appropriate for chronologhical ageappropriate for chronologhical age

Growth is parellal to curves but is lower Growth is parellal to curves but is lower than 3% .than 3% .

HAHA<<BABA==CACA

İdiopathic normal variant short İdiopathic normal variant short stature (nonfamilial short stature)stature (nonfamilial short stature)

Bone is not delayed, is appropriate for Bone is not delayed, is appropriate for chronologhical agechronologhical age

Growth is parellal to curves but is lower Growth is parellal to curves but is lower than 3% .than 3% .

Target height is not shortTarget height is not short

Constitutional growth and pubertal Constitutional growth and pubertal delaydelay

– Most common short satureMost common short sature– Mostyly in boysMostyly in boys– Family historyFamily history– Can be associated with familial short statureCan be associated with familial short stature– Growth velocity is slow in the first 3 years of life, they loss centile Growth velocity is slow in the first 3 years of life, they loss centile

gradually untill 2-3 years.gradually untill 2-3 years.– After they grow normal untill adolescent period.After they grow normal untill adolescent period.– Their weight gain is also slowTheir weight gain is also slow– HAHA==BABA< < CACA– Puberty develops later then expected normals, growth continues Puberty develops later then expected normals, growth continues

for a longer time than peers and their final height reaches their for a longer time than peers and their final height reaches their target height. target height.

– If pubertal delays beyond 16 years organic reasons should also If pubertal delays beyond 16 years organic reasons should also be thoughtbe thought

Pathologic short staturePathologic short stature

The most seldom and severe formThe most seldom and severe form

After 6 years GVAfter 6 years GV< 4,5cm/< 4,5cm/ year year

The first sign of chronic systemic disease The first sign of chronic systemic disease in the cessation of growth. One third of in the cessation of growth. One third of the patients admitting with short stature the patients admitting with short stature have systemic disease.have systemic disease.

İdiopathic normal variant short İdiopathic normal variant short staturestature

Familial Nonfamilial Const growth and pub delay

Differential diagnosis of normal and Differential diagnosis of normal and pathological short staturepathological short stature

İdiopathic normal İdiopathic normal variantvariant– <3%<3%– Height sds between Height sds between -2SD , -2SD ,

-3SD-3SD– GV is normal ( >6 years GV is normal ( >6 years

>4,5 cm>4,5 cm// year) year)– Parallel to growth curvesParallel to growth curves

Pathologic Pathologic – <1%<1%– Boy sds Boy sds > -3SD> -3SD– GV is subnormal(GV is subnormal(<<4,5 cm4,5 cm//

yyear)ear)– Growth is not parallel to Growth is not parallel to

curvescurves– Cessation of growth in any Cessation of growth in any

timetime

Pathological short staturePathological short stature

Term, BW<2500gr

PrenatalIUGR

Term, BW>2500gr

Postnatal

Proportional Disproportional

Skeletal dysplasia

Dysmofic synd

Systemic dis

yes no

Endocrine short stature

TFT Hypothyroidism

TFT euthyroidism

Growth hormone axis

Management of a child with Management of a child with short statureshort stature

Physical examination and anthropometric Physical examination and anthropometric mesurementsmesurements– Somatic abnormalities, proportion of the bodySomatic abnormalities, proportion of the body– Signs of chronic systemic diseaseSigns of chronic systemic disease– Height , sitting height, upper and lower segments, arm Height , sitting height, upper and lower segments, arm

span measurement, weight, bmıspan measurement, weight, bmı– Growth velocityGrowth velocity– Bone ageBone age– Target heightTarget height– Predicted adult height according to bone agePredicted adult height according to bone age

Height should be given as standart deviation Height should be given as standart deviation score (SDS) (z-score)score (SDS) (z-score)

SDS = measured height – mean height according to SDS = measured height – mean height according to gender and age / SDSgender and age / SDS

Target heightTarget height

Girls (cm)= Girls (cm)= (mat height+pat height)-13(mat height+pat height)-13

22

Boys (cm)=Boys (cm)=(mat height+pat height)-13(mat height+pat height)-13

22

TH TH ++ 8-10cm is what expected 8-10cm is what expected

In the first 6 months of life knee later left In the first 6 months of life knee later left wrist radiography wrist radiography

In skeletal dysplasias and in some In skeletal dysplasias and in some dysmorphic syndromes despite short dysmorphic syndromes despite short stature bone age may not be delayed. stature bone age may not be delayed.

LaboratuaryLaboratuary

Total blood countTotal blood countUrine density, urine evaluationUrine density, urine evaluationKidney and liver function testsKidney and liver function testsBlood gasesBlood gasesElectrolytes Electrolytes Calcium, phosphorus, alkaline phosphatase.Calcium, phosphorus, alkaline phosphatase.Celiac, antiendomysial, antigliadin Celiac, antiendomysial, antigliadin autoantibodiesautoantibodiesCreatine kinase (CPK)Creatine kinase (CPK)TFTTFT

PostnatalPostnatal

Proportional short statureProportional short stature

No systemic diseaseNo systemic disease

Euthyroid Euthyroid

Growth velocity < 4,5-5 cm/yGrowth velocity < 4,5-5 cm/y

Delay in bone age >2 yearsDelay in bone age >2 years

GH tests

Evaluation of growth hormone axis

No response to 2 pharm stim

Disturbed secretion in sleep

Bioinactive GHIGF-1 N or low20 % increase in IGF-1 levels in IGF1 generationtest

GH resistanceGH normal or increasedLow IGF-1 levels in IGF-1 generation testGH deficiency

Neurosecretory dysfunction

Growth hormoneGrowth hormoneMost of the cells in the pituitary are Most of the cells in the pituitary are somatotrophs.somatotrophs.One chain alpha-helical nonglicolized One chain alpha-helical nonglicolized polipeptid. polipeptid. 191 aminoasits and 2 intramolecular 191 aminoasits and 2 intramolecular disulfide connection.disulfide connection.22kDa molecular weight22kDa molecular weight 75% 75%20kDa20kDa 10-25%10-25%N-asetile and desamine forms N-asetile and desamine forms or or oligomersoligomers

Human growth hormone (hGH)Human growth hormone (hGH)

Nonpulsatile secretion in infantsNonpulsatile secretion in infants

GH secretion pulses and amplitude is decreased GH secretion pulses and amplitude is decreased and tonic secretion disappears untill puberty. and tonic secretion disappears untill puberty.

In puberty GH secretion amplitude increase In puberty GH secretion amplitude increase (gonodal steroids effect on GHRH)(gonodal steroids effect on GHRH)

Secretion of GH decrease with aging but is Secretion of GH decrease with aging but is secreted in whole life.secreted in whole life.

Growth homone effectsGrowth homone effects

İncrease protein synthesis, positive İncrease protein synthesis, positive nitrogen balancenitrogen balance

Lypolysis in fat tissueLypolysis in fat tissue

Decrease carbonhydrate utilization and Decrease carbonhydrate utilization and insulin sensivity insulin sensivity increase blood glucose increase blood glucose

GH effectGH effect

Binded to GH-binding protein (GHBP) (at least 50%)Binded to GH-binding protein (GHBP) (at least 50%)GHBP,is the extracelluar part of GH-R .GHBP,is the extracelluar part of GH-R .

IGF-1 levels are decreasedIGF-1 levels are decreased

GH deficiencyGH deficiency

Hypothyroidism Hypothyroidism

MalnutritionMalnutrition

Chronic diseasesChronic diseases

IGF’s bind to binding proteins (IGFBP).IGF’s bind to binding proteins (IGFBP).– t ½t ½– Transport to target tissueTransport to target tissue– Modifiy the relation between IGF and its rec Modifiy the relation between IGF and its rec – 6 different IGFBP are cloned6 different IGFBP are cloned– IGFBP-3 90%, depends on IGF-1IGFBP-3 90%, depends on IGF-1

IGF-1 recIGF-1 rec– StructurallyStructurally similiar to insulin rec (2 alfa,2beta similiar to insulin rec (2 alfa,2beta

subunits)subunits)

GHGH

IGF’s (somatomedins)IGF’s (somatomedins)– Similar to proinsulinSimilar to proinsulin– Effect on extracellular growth is mediated by Effect on extracellular growth is mediated by

IGF-1 IGF-1 (70aa polipeptid) (70aa polipeptid)

Factors that increase growth Factors that increase growth hormone secretionhormone secretion

GHRHGHRHArginine, leucin Arginine, leucin Alpha adrenergic agonistler (alfa 2 Alpha adrenergic agonistler (alfa 2 adrenargic)adrenargic)Beta adrenergic antagonistsBeta adrenergic antagonistsDopamine, acetylcholineDopamine, acetylcholineHypoglycemia Hypoglycemia Sleeping Sleeping Exercise Exercise

Factors that decrease growth Factors that decrease growth hormone secretionhormone secretion

Hyperglycemia Hyperglycemia

ObesityObesity

İncrease in free fatty acidsİncrease in free fatty acids

Glucocorticoid excessGlucocorticoid excess

Hypothyroidism Hypothyroidism

İncrease in adrenargic tonusİncrease in adrenargic tonus

Psychosocial deprivitionPsychosocial deprivition

Growth hormoned stimulation Growth hormoned stimulation teststests

Pharmacologic stimulationPharmacologic stimulation– GH response GH response < < 5 ng/ml 5 ng/ml complete GH defcomplete GH def– GH response 5GH response 5-10 -10 ng/mlng/ml partial GH defpartial GH def– GH response GH response >>10ng/ml10ng/ml normalnormal

At least no response to 2 stimuliAt least no response to 2 stimuli

Growth hormone deficiencyGrowth hormone deficiency

Congenital growth hormone deficiency Congenital growth hormone deficiency incidence1:4000 -1:10,000 live birthincidence1:4000 -1:10,000 live birth

Stunded growth Stunded growth


Mild deficiencyMild deficiencySymptoms after the first 6 months of life . After the Symptoms after the first 6 months of life . After the disappearence of maternal hormonesdisappearence of maternal hormonesNormal birth lengthNormal birth lengthGrowth velocity decrease gradually Growth velocity decrease gradually Bone age delaysBone age delaysPeriabdominal fat tissue increasePeriabdominal fat tissue increaseLess muscle mass Less muscle mass Teeth development is delayedTeeth development is delayedThin hair, delay in nail growingThin hair, delay in nail growing


Severe deficiencySevere deficiency– Newborn period Newborn period

Hypoglycemia Hypoglycemia

Conjugated hyperbilirubinemiaConjugated hyperbilirubinemia

Micropenis (multiple pituitary hormone deficiency)Micropenis (multiple pituitary hormone deficiency)

Treatment Treatment

Konstitutional growth and pubertal delayKonstitutional growth and pubertal delayBoys : Testesterone enantate 50-100mg/ months Boys : Testesterone enantate 50-100mg/ months IM for 3-4 monthsIM for 3-4 months

Girls: Ethynylestradiol 10-20Girls: Ethynylestradiol 10-20µµg/ day for 3-4 monthsg/ day for 3-4 months

GH deficiencyGH deficiency– GH 0,2mg/kg/ week, in the management of GH 0,2mg/kg/ week, in the management of

pediatric endocrinologistpediatric endocrinologist

Download - Short stature Dr Olcay Evliyaoğlu. Definition Height lower than 3 % in growth charts(

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