1. Short stature
Dr Olcay Evliyaoğlu

2. Definition Height lower than 3 % in growth charts(<-2sd)
Severe short stature: Height lower than 1% (< -3sd)

3. Etiologic classification of short stature
Normal
Constitutional growth retardation
Familial short stature
Both

4. Etiologic classification of short stature
Pathologic
Nutritional
Malnutrition
Malabsorption
Celiac disease
Zinc deficiency
Enflamatuary bowel disease

5. Etiologic classification of short stature
İntrauterine growth retardation
Sporadic
Dysmorphic syndrome
Chromosomal abnormalities ( Silver-Russel, Down, Seckel etc)
Skeletal dysplasias
Metabolic disease
Mucopolysaccharidosis
Other storage disease

6. Etiologic classification of short stature
Chronic diseases
Chr renal disease
Chr liver disease
Congenital heart disease
Pulmonary diseases ( cystic fibrosis, branchial asthma)
Chr infections
Psychosocial dwarfism

7. Etiologic classification of short stature
Drugs
Glucocorticoids
Estradiol ve androgens
Endocrine short stature
Hypothyroidism
GH deficiency
Hypopituitarism
Excess cortisol
Pseudohypoparathyroidism

8. Etiologic classification of short stature
Dysmorphic syndromes with short stature
Turner
Noonan
Aarskog
Disproportional short stature
Skeletal dysplasias
Congenital abnormalities

9. İdiopathic normal variant short stature (familial short stature)
Genetics determine
Target height is short
Bone age is not delayed, and is appropriate for chronologhical age
Growth is parellal to curves but is lower than 3% .
HA<BA=CA

10. İdiopathic normal variant short stature (nonfamilial short stature)
Bone is not delayed, is appropriate for chronologhical age
Growth is parellal to curves but is lower than 3% .
Target height is not short

11. Constitutional growth and pubertal delay
Most common short sature
Mostyly in boys
Family history
Can be associated with familial short stature
Growth velocity is slow in the first 3 years of life, they loss centile gradually untill 2-3 years.
After they grow normal untill adolescent period.
Their weight gain is also slow
HA=BA< CA
Puberty develops later then expected normals, growth continues for a longer time than peers and their final height reaches their target height.
If pubertal delays beyond 16 years organic reasons should also be thought

12. Pathologic short stature
The most seldom and severe form
After 6 years GV< 4,5cm/ year
The first sign of chronic systemic disease in the cessation of growth. One third of the patients admitting with short stature have systemic disease.

13. İdiopathic normal variant short stature
Nonfamilial
Const growth and pub delay
Familial

14. Differential diagnosis of normal and pathological short stature
İdiopathic normal variant
<3%
Height sds between -2SD , -3SD
GV is normal ( >6 years >4,5 cm/ year)
Parallel to growth curves
Pathologic
<1%
Boy sds > -3SD
GV is subnormal(<4,5 cm/ year)
Growth is not parallel to curves
Cessation of growth in any time

15. Pathological short stature
Term, BW<2500gr
Term, BW>2500gr
Prenatal
IUGR
Postnatal
Proportional
Disproportional
Systemic dis
Skeletal dysplasia
Dysmofic synd
yes no
Endocrine short stature
TFT
euthyroidism
TFT
Hypothyroidism
Growth hormone axis

16. Management of a child with short stature
Physical examination and anthropometric mesurements
Somatic abnormalities, proportion of the body
Signs of chronic systemic disease
Height , sitting height, upper and lower segments, arm span measurement, weight, bmı
Growth velocity
Bone age
Target height
Predicted adult height according to bone age

17. Height should be given as standart deviation score (SDS) (z-score)
SDS = measured height – mean height according to gender and age / SDS

18. Target height
Girls (cm)= (mat height+pat height)-13 2
Boys (cm)=(mat height+pat height)-13

19. TH + 8-10cm is what expected

20. In the first 6 months of life knee later left wrist radiography
In skeletal dysplasias and in some dysmorphic syndromes despite short stature bone age may not be delayed.

21. Laboratuary Total blood count Urine density, urine evaluation
Kidney and liver function tests
Blood gases
Electrolytes
Calcium, phosphorus, alkaline phosphatase.
Celiac, antiendomysial, antigliadin autoantibodies
Creatine kinase (CPK)
TFT

22. Proportional short stature No systemic disease Euthyroid
Postnatal
Proportional short stature
No systemic disease
Euthyroid
Growth velocity < 4,5-5 cm/y
Delay in bone age >2 years
GH tests

23. Evaluation of growth hormone axis
Bioinactive GH
IGF-1 N or low
20 % increase in IGF-1 levels in IGF1 generation
test
GH resistance
GH normal or increased
Low IGF-1 levels in
IGF-1 generation
test
No response to 2 pharm stim
Disturbed secretion in sleep
GH deficiency
Neurosecretory dysfunction

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

25. Human growth hormone (hGH)
Nonpulsatile secretion in infants
GH secretion pulses and amplitude is decreased and tonic secretion disappears untill puberty.
In puberty GH secretion amplitude increase (gonodal steroids effect on GHRH)
Secretion of GH decrease with aging but is secreted in whole life.

26. Growth homone effects
İncrease protein synthesis, positive nitrogen balance
Lypolysis in fat tissue
Decrease carbonhydrate utilization and insulin sensivity  increase blood glucose

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

28. IGF-1 levels are decreased
GH deficiency
Hypothyroidism
Malnutrition
Chronic diseases

29. IGF’s bind to binding proteins (IGFBP).
Transport to target tissue
Modifiy the relation between IGF and its rec
6 different IGFBP are cloned
IGFBP-3 90%, depends on IGF-1

30. IGF-1 rec
Structurally similiar to insulin rec (2 alfa,2beta subunits)

31. GH IGF’s (somatomedins) Similar to proinsulin
Effect on extracellular growth is mediated by IGF-1 (70aa polipeptid)

32. Factors that increase growth hormone secretion
GHRH
Arginine, leucin
Alpha adrenergic agonistler (alfa 2 adrenargic)
Beta adrenergic antagonists
Dopamine, acetylcholine
Hypoglycemia
Sleeping
Exercise

33. Factors that decrease growth hormone secretion
Hyperglycemia
Obesity
İncrease in free fatty acids
Glucocorticoid excess
Hypothyroidism
İncrease in adrenargic tonus
Psychosocial deprivition

34. Growth hormoned stimulation tests
Pharmacologic stimulation
GH response < 5 ng/ml complete GH def
GH response 5-10 ng/ml partial GH def
GH response >10ng/ml normal
At least no response to 2 stimuli

35. Growth hormone deficiency
Congenital growth hormone deficiency incidence1: :10,000 live birth
Stunded growth

36. Growth hormone deficiency
Mild deficiency
Symptoms after the first 6 months of life . After the disappearence of maternal hormones
Normal birth length
Growth velocity decrease gradually
Bone age delays
Periabdominal fat tissue increase
Less muscle mass
Teeth development is delayed
Thin hair, delay in nail growing

37. Growth hormone deficiency
Severe deficiency
Newborn period
Hypoglycemia
Conjugated hyperbilirubinemia
Micropenis (multiple pituitary hormone deficiency)

40. Treatment Konstitutional growth and pubertal delay GH deficiency
Boys : Testesterone enantate mg/ months IM for 3-4 months
Girls: Ethynylestradiol 10-20µg/ day for 3-4 months
GH deficiency
GH 0,2mg/kg/ week, in the management of pediatric endocrinologist