Presentation on Approach to short stature.pptx

Short stature

1. Short stature SUGANTHA KUMAR T

2. Heightism Being short worries parents, children and pediatricians Psychosocial aspects Professional aspect Medical implications Growth failure may be the first and only sign of an underlying medical illness.

3. OUTLINE Normal growth and monitoring Definition When to suspect short stature Establishing true short stature - Measurements Height velocity Classification and etiology Normal variants Diagnostic approach GHD GH treatment and titration Case scenario Take Home Message

4. 1.NORMAL GROWTH AND MONITORING

5. Normal Growth: – Factors Responsible Is a composite effect of - Adequate nutrition Normal genetic constitution Sufficient hormone (growth hormone, thyroid hormone, cortisol and etc..) Absence of chronic illness Psychosocial wellbeing

6. When To Measure Growth Parameters In Normal children ? Different Guidelines

7. AAP Guidelines Age Monitoring Up to 6 mths 2 monthly 6 – 18 mths 3 monthly till 18 yrs of age every yr First 24 mths – Supine length. Thereafter – Erect height. 2-3 years ?

8. IAP Guidelines Age Growth parameters SMA,Penile length,BMI 0- 18 months Immunization visit A t birth 18 – 3 years 6 monthly 4-8 years 6 monthly yearly 9- 18 years yearly yearly

9. 2.SHORT STATURE- Definitions

10. Short Stature- Defined as Height < 3 rd percentile (<-2 SD for age /sex /population). OR Height below genetic potential (<-2 SD of target height). OR Slow growth velocity (< 5 cm/yr from age 3 yrs to puberty). OR Height velocity (< 25 th centile ). OR Downwardly crossing percentile channels on growth chart (after 18 months).

11. Other Definitions- Chronological Age: Calendar age of the patient Height Age Age at which patient ’ s height is at the 50 th percentile Weight Age Age at which patient ’ s weight is at the 50 th percentile Bone Age Age at which skeletal maturation shown in patient ’ s radiograph is normally attained

12. Height Age is 6 yrs 9yrs/M, Ht - 115 cm

13. Short Stature Cont - WHO definition - Stunting: Height-for-age <-2SD & >-3SD Severe stunting: Height-for-age <-3SD Any difference between short stature and stunting ?

14. 3.ESTABLISHING TRUE SHORT STATURE What To Measure How To Measure When To Measure

15. Measuring Growth parameters:- Length /height Weight for height US/LS Arm span

16. Measuring Growth- Length Equipment- Infant Length Board ( Infantometer ) Measured from the vertex (highest point on skull) to the soles of the feet. Measure length to 0.1 cm November 2002, Volume 56, Number 11, Pages 1119-1125 Diet and nutritional status of rural adolescents in India fixed headpiece movable foot piece legs should be fully extended eyes should be looking up

17. Measuring Growth - Height Stadiometer Standing height is measured between the vertex and the floor. Heels together, barefoot Back of head Thoracic spine, Buttocks & Heels Head in Frankfurt plane

18. Weight For Height :- Sensitive index of current nutritional status. Less variable due to age, ethnicity. Differentiate between endocrine and chronic disorders Is it needed ?

19. US/LS Ratio Lower segment- distance between upper border of sym.pubis and floor Upper segment- subtracting lower segment from total height Obese children- sitting height

20. How To Measure:- Pubic symphysis Floor Top of head Upper segment Lower segment height Significance ?

21. Which Growth Chart To Be Used ?

22. NEW WHO Growth Standards 2006 Breast fed children Norway , U.S ,Brazil ,India ,Oman ,Ghana . WHO growth charts are excellent ,recent, up- to- date, multicentre , multinational reference charts . Ideal growth chart to be used for children up to 5 yrs of age Avaible up to 19 years IAP/WHO / CDC but which ever use, must be follow on same chart (best locally adapted)

23. 4.SHORT STATURE Cont. When To Suspect

24. Always Suspect :- When child is too short compared to his/her peers of same age When a child younger his/her age is taller than him When the child’s height is less than 3rd percentile for his/her age and sex Height velocity < 25 th centile for last 6-12 month

25. Chief Complaints :- Short for age in comparison to peers Failure to gain height Arrest of normal gain of height

26. 5.SHORT STATURE -Classification Prerequisite

27. Expected Height- The Genetic P otential Midparental Target height Boys: [father’s height in cm + (mother’s height in cm + 13 cm)]/2 Girls: [(father’s height in cm – 13 cm) + mother’s height in cm]/2

28. 10 cm above 10 cm below 105cm and 8 yrs Extrapolated height along growth curves 155 cm

29. Height velocity More Accurate Indicator Of Growth and Stature Assessment

30. Height velocity Cont Genetic potential attained at 24 months Abnormal GV after 2 years is not normal Height measurements performed at 6-month intervals Measured over 1 year in Cm/year.

31. Normal Growth Velocities During Human Development:- Life stage Average Growth Velocity / Year. In utero 60-100 cm( 1.2 -1.5 cm/ wk ) 1 st year 23-27 cm 2 nd year 10-14 cm 3 rd & 4 th year 6-7 cm 5 years- till onset of puberty 5cm – 5.5 cm Puberty 10-12 cm (G<B)

32. Growth Velocity –Pubertal burst :-

33. 5.SHORT STATURE – Classification Cont

34. Short stature Pathological Normal variants -Constitutional -Familial Proportionate Disproportionate -Skeletal dysplasia -Rickets Prenatal -IUGR -Dysmorphic -Chromosomal Postnatal -Malnutrition -Chronic disease - Endocrine -Psychosocial -Drugs

35. 6.SHORT STATURE Normal Variants

36. Normal Variants Familial short stature Constitutional delay of growth and puberty Differentiated by- Sequence of CA/BA/HA Height velocity Puberty timing Presentation height /Final height Clinical character Constitutional delay Familial short stature Height Short Short CA/HA/BA CA>BA=HA CA=BA>HA Growth rate Slow Normal Puberty Delayed At usual age Family h/o Delayed puberty Short stature Height prognosis Good Poor

37. Growth Chart For Normal Variants

38. Case-1 8yr female child, short stature . No dysmorphism , proportionate. No history of chronic illness . Family history of short stature . Normal growth rate . No delay in bone age .

39. HA < BA=CA 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 X =BA Familial short stature

40. Case -2 7 yr male with short stature . No dysmorphism but proportionate . Wt for ht normal. Screening normal . Family history of delayed puberty . No h/o chronic illness . Slow growth rate . Mild delay in bone age .

41. HA=BA < CA TH 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 8 =BA Constitutional Delay Of Growth And Puberty (CDGP)

42. 7.Short stature When To Suspect Pathology

43. Should Suspect Pathology Child height< 0.4 th centile( < -3SD). Abnormally short for family heights. History/exam suggests chronic illness. (especially weight loss more than height loss) Abnormal growth velocity Body proportions abnormal Dysmorphic features or midline defects

44. Pathologic Short Stature cont It’s uncommon and a severe form After 6 years GV < 4.5cm/ year May be first sign of chronic systemic disease in the cessation of growth. One third of the patients admitting with short stature have systemic disease.

45. Path causes -1.Short &Thin (FTT) Cardiovascular – congenital heart disease Respiratory – cystic fibrosis GIT – Inflammatory bowel disease, Coeliac disease Liver – liver cirrhosis Renal – Renal Failure Hematology – Iron deficiency anemia, thalassemia Infection Abused or neglected Ask for detailed history and appropriate physical examination

46. 2 .Small for Gestational Age (SGA) :- Birth weights <10 th percentile of the same gestational age infants born as AGA May have increased concentrations of GH and have low levels of IGF-I and IGFBP-3, s/o GH insensitive 80-90 % catch up in growth by the age of 2-3 year 10-20 % Remain short – need evaluation

47. 3.Short and plump :- Genetic Syndromes Endocrinopathies Intrinsic Short Stature :- SGA Genetic causes

48. Case-3,Identify ? Investigation Karyotyping USG abdomen Turner Syndrome

49. Case -4 A 6yr old boy is brought to your practice by his paternal grandparents for his first visit. You note that the child is short for his age, has down-slanting palpebral fissures, ptosis, low set and malformed ears, abroad and webbed neck, shield chest and cryptorchidism. You hear a systolic ejection murmur in the pulmonic region. He has speech therapy for speech delay.

50. 3.GENETIC CAUSES :- Abnormal Appearance PRIMORDIAL DWARISM CHROMOSOMAL SKELETAL DYSPLASIA Silver-Russell Seckel syndrome Osteo dysplastic Meier gorlin syndrome Turner syndrome Down syndrome Noonan syndrome Prader-Willi syndrome Rhizomelic Achondroplasia Hypochondroplasia Acromelic Acro dysostosis Mesomelic Robinow syndrome Metaphysial dysplasia Rickets Spondylometa dysplasia MPS Mucolipidosis

51. 3.Short & Plump - Endocrinopathies Hypothyroidism Precocious Puberty Cushing Syndrome (endogenous/iatrogenic) Diabetes Mellitus Hypogonadism Decreased GH action GH def – Isolated/ Panhypopituitarism , Congenital/Acquired GH insensitivity – Laron dwarfism

52. Causes – MENOMICS E ndocrine P sychosocial I atrogenic C hronic illness N utritional I UGR C hromosomal S keletal dysplasias Hypothyroidism Growth hormone deficiency Cushing syndrome Child abuse Marital conflicts Spinal irradiation Steriods Renal –RTA,CRF. GIT- IBD,celiac . Hematological Metobolic Cystic fibrosis CHD PICNICS

53. 8.SHORT STATURE Clinical Evaluation

54. History Child’s History : Duration Perinatal history – antenatal & natal complications, birth wt History or signs/symptoms of systemic illness Signs of puberty Syndromic features

55. … Contd Family History : Parents’ heights Parents’ age of puberty H/o short stature and chronic disorders H/o delayed growth or puberty H/o any consanguinity.

56. … Contd Dietary history – Protein calorie intake Medication history Steroids Dentition history Psychosocial history

57. Examination Vitals- pulse rate ,B.P. Anthropometry, MPH, Bone Age, Growth Velocity General Physical Examination Systemic Examination Dysmorphism Thyroid size Genitalia/ SMR Signs of abuse Tone reflexes Vision Organomegaly

58. 9.SHORT STATURE :- Body Proportions Upper Segment And Lower Segment Ratio Arm Span

59. US/LS Ratio Changes :- AGE RATIO BIRTH 1.7 : 1 6 m 1.6 : 1 2 y 1.5 : 1 3 y 1.3 : 1 7 – 8 y 1 : 1 Adult 0.8-0.9

60. Significance Of US/LS Ratio:- US>LS Achondroplasia Rickets Hypothyroidism LS>US Arachnodactyly/ Marfans Spondyloepiphyseal dysplasias Mucopolysaccharidoses Potts spine Skeletal survey ACHONDROPLASIA Diagnosis ?

61. Diagnosis ? Mucopolysaccharodosis Skeletal survey Case-7

62. Arm Span Distance between tips of middle fingers of both arms outstretched at right angles to body Across back/on wall Under 5 children : span <height (1-2 cm ) 10-12 yr : span=height Adults : span > height (by 2 cm )

63. Arm Span:- Arm span more than height- Disease of vertebrae/ marfans syndrome Kleinfelter syndrome /Co- arctation of aorta Eunachoidism / Arachnodactyly Arm span less than height- Achondroplasia, Hypochondroplasia Turner syndrome

64. Surrogate Marker Of Height :- Scoliosis Spinabifida Leg contractures Spinal irradiation

65. 10.Bone Age Age At Which Skeletal Maturation Takes Place Why Important ?

66. Which Bones To Evaluate? Newborn – Knee (Distal epiphysis of femur- 31-39 wks , Proximal epiphysis of tibia- 34-45 wks ) 3 to 9 mth – Shoulder ( Humerus upper end- 3-9 mo ) 1 to 13 yrs – Hands and Wrists 12 to 14 yrs – Elbow and Hip “Bone Age is more advanced in girls compared with boys ”

67. Bone Age ( Contd …) 9 years: olecranon 11 years: lateral condyle humerus 12 years: lesser tochanter 13 years: triradiate cartilage acetabulum 14 years: iliac crest 15 years: acromion 16 years: ischial tuberosity 18 years: inner end clavicle

68. Bone Age Significance:- Significant delay – GH deficiency Hypothyroidism Celiac disease Mild delay –----  Constitutional SS Appropriate - --  Familial SS Down syndrome Turner syndrome Skeletal dysplasia A deviation of bone age upto 20% may still be normal

69. Bone Age- Additional Aspect Greulich & Pyle standards- Most commonly used method. Delayed BA merely indicates that the associated short stature is to some extent “partially reversible” because linear growth continues until epiphyseal fusion is complete. Never diagnostic .

70. If Bone Age Is Normal - Possibilities (overall guarded prognosis) to be considered are Skeletal dysplasias Genetic syndromes Idiopathic short stature (diagnosis of exclusion) Further work up Skeletal survey- X-Ray long bones, spine, skull, pelvis Genetics referral, search for dysmorphism

71. Case-8 A 4 yr old child has mental retardation, shortness of stature, brachydactyly (especially of the fourth and fifth digits) and obesity with round facies and short neck. The child is followed by an ophthalmologist for sub-capsular cataracts and has previously been noted to have cutaneous and subcutaneous calcifications, as well as perivascular calcifications of the basal ganglia .

72. 11.Need of Systemic Radiology :- Need of Skeletal Survey Skull (AP,LAT) Spine( AP,Lat ) Thorax (AP) Pelvis (AP) Upper limb/Long bones (AP) Left hand and wrist (PA) Lower limb (AP) ,Ankle/Knee( Lat ) Disproportionate

73. Skeletal Survey- To Look For.. Malformations (spina bifida, klippel feil syndrome) Dysplasias - affected segment- long bones ( rhizo / meso / acromelia ), flat bones, skull/pelvis, spine Evidence of metabolic bone disease- RTA, Hypoparathyroidism

74. ROLE OF RADIOLOGY Campomelia Case-9

75. 12.SHORT STATURE- Diagnostic Approach Algorithm Flow Charts

76. SHORT STATURE (HSDS <–2 ) Malnutrition Organic diseases Endocrine disorders SGA without catch-up Metabolic disorders Psychosocial disturbances Iatrogenic causes Achondroplasia Dyschondrosteosis Mucopolysaccharidosis Osteogenesis imperfecta rickets spondylodysplasia Idiopathic short stature Height >-2.0 SD belowTH and/or Height deflection >1 SD. BA/CA < 0.8 Dysmorphic features Disproportion No dysmorphy or disproportion Yes No Syndrome Wt/ht preserved –endocrine Wt/ht decreased – non endocrine Assurance/f/u /GHT

77. 12.SHORT STATURE-Diagnosis cont Investigations Algorithm

78. SHORT CHILD History examination Anthropometry Growth velocity Mid parental height Bone age Specific clue Normal variant Specific diagnosis yes No, < -3SD LEVEL-1 Complete Hemogram Ca +2 , Po 4 , ALP Na + , K + , Cl - LFT, RFT,CXR,MtX Urine R/E Stool R/E Blood Gas Abnormal and wt/ht affected LEVEL -3 tTTG,IGF-1,IGFBP-3 GHSt ,MRI LEVEL-2 Thyroid profile. Karyotyping (female) Specific treatment Referral to endocrinologist

79. 13.Short stature Growth Hormone Deficiency

80. Growth Hormone Deficiency 1/3500-4000 Cherubic / doll like facies Midfacial crowding / Depressed nasal bridge Round facies Weight – normal or mildly obese Micropenis Delayed tooth eruption Look younger

81. Evaluation of growth hormone axis No response to 2 pharm stim Disturbed secretion , decrease in sleep level 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 GH deficiency Neurosecretory dysfunction GH resistance GH Bioinactive IGF-1 Deficiency IGF-1 Level low IGGBP-3 level low

82. Diagnostic Confirmation –GH Stimulation Test Indication- Postnatal Proportional short stature No systemic disease Euthyroid Growth velocity < 4 . 5-5 cm/y Delay in bone age >2 years

83. GH Stimulation Test Done with - Minimum two stimulation agent Insulin , Clonidine, Arginine Results interpretation:- 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 Single gold standard test for GHD diag ? GH stimulation result IGF-1 /IGFBP-3 level MRI

84. 14.SHORT STATURE Treatment

85. Depend On Etiology Familial short stature Reassurance / can try GHT C onstitutional growth and pubertal delay Boys : Testesterone enantate 50-100mg/ months IM for 3-4 months Girls: Ethynylestradiol 10-20 µ g/ day for 3-4 months Treat underlying condition Nutritional Rehabilitation Social Rehabilitation, Councelling,Behavioral therapy Treatment of infections, Hormone supplementation Vit D - Ricke ts GH deficiency - GH T by pediatric endocrinologist

86. 6yr mch , Normal at birth later had severe growth retardation is proportionate with hypo-plastic genitals and small fingers and nails . Screening normal Delayed bone age GH stimulation test Resting and stimulated growth hormone high Laron syndrome or growth hormone insensitivity Case-9,Identify

87. Word On IGF-1 :- Levels Are Decreased GH deficiency Hypothyroidism Malnutrition Chronic diseases IGF’s bind to binding proteins (IGFBP). Transport to target tissue Modifiy the relation between IGF and its rec eptor 6 different IGFBP are cloned IGFBP-3 90%, depends on IGF-1

88. Growth Hormone Deficiency - C/F 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 Severe deficiency - Newborn period Hypoglycemia Conjugated hyperbilirubinemia Micropenis (multiple pituitary hormone deficiency)

89. 15.Short Stature(GHD)-Treatment Growth Hormone Therapy

90. GHT– Indication & Doses (mic/kg/day) GHD Children 25-50 Adolescent 25-100 Adult 6-25 CKD 50 Turner syndrome 50 SGA 50-70 PWS 35-50 Noonan Syndrome 50 SHOX gene SS 30- 50

91. Growth Hormone Therapy cont Effect reduces with time; esp after 3 years ? Formation of antibodies ? Hypothyroidism Side effects more common in adults Need dose titration to achieve maximum height potential Monitoring -1.IGF LEVEL 2. Titration as per response ( dose/kg)

92. GHT- Side Effects Hyperglycemia Slipped capital femoral epiphysis Pseudotumor cerebri Hypothyroidism, Adrenal insufficien Edema Hypertension Melanocytic nevi Arthralgia Myalgia, Muscle stiffness Paresthesias

93. GHT Cont – Out come ? 1/3 poor responders, 1/3 respond as expected (gain 5-10 cm ) 1/3 excellent responders Good Predictors: Good growth velocity- 1st year Tall parents

94. GHT cont. – Response deciders Response better if started earlier Average increment = 10 cm/year Total increment: 20-30 cm Better response in classic GHD Higher dose needed in Turner syndrome

95. GHT Cont - If Poor Response ? Compliance Dose /Technique Associated other hormone deficiency Underlying pathological disease uncorrected GH resistant or receptor mutation Wrong diagnosis

96. 16. GHT cont . - Duration of therapy Stop or not ? If yes when ? Stop when ht gain < 2 cm/ yr or BA matured Life long for complete GHD Partial GHD- Reassess and decide for GHT for adult

97. SHORT STATURE Some More Questions

98. History examination Anthropometry Growth velocity Mid parental height Bone age Complete Hemogram Ca +2 , Po 4 , ALP Na + , K + , Cl - LFT, RFT Urine R/E Stool R/E Blood Gas Thyroid profile. GH stimulation test. Karyotyping (female) 5 yr mch ,poor gain in weight and height,Birth weight Wt<3 centile ,Ht <3 rd centile , wt/ht decreased Bone age is mildly delayed , Proportionate Target height is less than -2SD Case- scenario for evaluation Malnutrition Renal GIT Anemia Low albumin levels Stool ph acidic Malabsorbtion syndrome tTGA and biopsy S/O CELIAC disease CHRONIC DISORDERS

99. What Is The Expected Height ? Father 170 Mother 150 Male Female 166.5 153.5

100. Rapid fire revision Bone age delayed in CGD/FSS- Normal adult height - Growth promoting actions of growth hormone are mediated by – Birth weight of congenital growth hormone deficiency – Catch up growth attained at- IGF - 1 Normal CGD CGD 24 months

101. References Nelson textbook of pediatrics Brook’s pediatric endocrinology IAP pediatric endocrinology Guidelines –NICE/ACMG/EMEA Williams endocrinology

102. Take Home Message:- Most apparently healthy children who have short stature but are growing at a normal growth velocity are normal and healthy. Most important for growth assessment is growth velocity. Slowed growth rate rarely normal. During the first 3 years after birth and puberty, most changes on the linear growth curve are normal

103. Thank You