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approach to short stature

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approach to short stature

  1. 1. APPROACH TO A CHILD WITH SHORT STATURE DR.V.V.RATNAKAR REDDY dr m mallikarjuna
  2. 2. Why we need to concern?• BECAUSE…………………..IT CAN BE A SIGN OF DISEASE, DISABILITY, & A SOCIAL STIGMA CAUSING PSYCHOLOGICAL STRESS
  3. 3. Definition A child whose height is below 2 standard deviations for age and gender Males 200 78 190 +2 +1 74 Generally 180 0 70 accepted 170 -1 160 -2 66 -2.0 SD (2.3 percentile) definition of 62 normal rangeHeight (cm) 150 Height (in) 58 140 54 130 50 120 46 110 42 100 38 90 34 80 30 70 2 4 6 8 10 12 14 16 18 20 Age (y )
  4. 4. Definition: • Height below 3rd 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 25th 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. • Pediatrics,EssentialIIIIIIIII 7 Edition, OP Ghai; Fima Lifschitz- Pediatric Endocrinology th
  5. 5. Growth Physiology EnvironmentGenetic factors Growth Hormones •Growth hormone •Thyroid hormone Dietary factors •Gonadotrophins
  6. 6. Factors affecting height Intra FSHuterine Nutrition LH Growth HormoneGrowth Thyroid harmone GHfactors Thyroid Birth 1 year 2 years 4years 8years Puberty Adult
  7. 7. Growth factors at various stages• PRENATAL GROWTH:Uterine function & size, maternal nutrition, insulin,IGF/BP• POSTNATAL GROWTH:GH& THYROXINERapid linear growth velocity initially that declines progressively after birth to 3 yrs.25cms  12.5cms->8cm/yr.
  8. 8. • 3YEARS TO PUBETY:GH& THYROID HORMONEConstant linear growth @4-7cm/yr.• PUBERTY:Sex steroids(estrogen&testosterone) in concert with GH,THYROID,&NUTRTION Acceleration of growth pubertal growth spurt.- Spontaneous growth hormone elevation in response to sex steroids.
  9. 9. • First sign of puberty in females preceeds the first sign of puberty in males by 6months.• Pubertal growth spurt in females is 2 years earlier than males but the peak height velocity is slower in females than males(8.3cm/yr <9.5cm/yr) resulting in on an average of 13cm difference in between them.
  10. 10. SKELETAL MATURATION• Growth usually results from increased length of bones coupled with rate of skeletal maturation.• BONE AGE RADIOGRAPHY:Assessing skeletal maturation by examining the epiphyseal maturation at hand&wrist.In <18 months- hemiskeleton x ray due to immature hand &wrist growth plates.• Delayed bone age –indicates short stature is partially reversible coz linear growth continues until epiphyseal fusion completes.
  11. 11. Normal height pattern• Birth length 50cm• One year 75 cm• Two yrs 87.5 cm• Three yrs 93.75 cm growth• 4 yrs 100 cm velocity• 8 yrs 125 cm 6 cm• 12 yrs 150 cm per year
  12. 12. NORMAL GROWTH• The most critical factor in evaluating the growth is determining GROWTH VELOCITY.• Observation of childs height pattern in the form of “CROSSING PERCENTILE LINES” on a linear growth curve is the simplest method of observing abnormal growth velocity.• Atleast 3 measurements with preferably 6 months intervel in between is necessary to comment on growth pattern.• A short child with non delayed bone age is of much more concern.
  13. 13. SHORT STATURE Dysmorphic Normal Dis- Proportionate Proportionate•Russle Silver •Constitutional •Osteogenesis•Noonan’s •Familial/genetic imperfecta•Turner syndrome •IUGR •Achodroplasia•Downs syndrome •Ch Malnutrition •Rickets•Prader Willi •Celiac Disease •Metabolic and•Pseudo- •Chronic systemic storage disordershypoparathyroidism disease (CRF, CLD) (short spine) •GH Deficiency •Hypogonadism •Hypothyroidism
  14. 14. Short Child That Looks Normal Calculate TH Not Within Target Range Within Target Range Watch GV Observe – GV NormalNormal growth velocity Low growth velocity Low birth weight Chronic systemic disease Growth delay Endocrine disorder Idiopathic SS Genetic, chromosomal Psychosocial
  15. 15. Causes Of Short Stature: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)
  16. 16. iii) Psychosocial Short Stature (emotional deprivation)iv) Endocrine Causes: (With increased W/H) - Growth Hormone Deficiency/ insensitivity - Hypothyroidism - Juvenile Diabetes Mellitus - Cushing Syndrome - Pseudohypoparathyroidism
  17. 17. 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
  18. 18. ComparisonFeature Familial Short Stature Constitutional Short Stature1) Sex Both equally affected More common in boys2) Length at Birth Normal( crosses percentile Normal (starts falling <5th downwards by 3yrs) centile in 1st 3yrs of life)3) Family History Of short stature Of delayed puberty4) Parents Stature Short (one or both) Average5) Height Velocity < NORMAL but gains >4cm/yr Normal6) Puberty Normal Delayed7) Bone Age & Chronological BA = CA > Height Age CA > BA = Height Age Age8) Final Height Short, but normal for target Normal due to normal growth height in pre pubertal years.
  19. 19. Genetic Syndromes: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 childSeckle syndrome- bird headed dwarfism.B) Inborn Errors of Metabolism -eg. Galactosemia, Aminoaciduria
  20. 20. Intra-uterine Growth Restriction• Arrest of fetal growth in early embryonic life causes reduction in total number of cells, leading to diminished growth potential in postnatal life• BW -<10th centile for GA.• Most of these babies show catch-up growth by 2yrs of age, but 20-30% may remain short.• AETIOLOGY: Subtle defects in the GH-IGF axis• Growth Velocity- normal• BA = CA• Learning disabilities could be present
  21. 21. Under nutrition:• One of the commonest cause of short stature in India.• Aetiology: PEM, Anemia & trace element deficiency such as Zinc , calcium def are common causes.• Child usually appear STUNTED, with POOR Wt. gain, Wasted muscles.• BA < CA.:• Usually child achieves catch up growth with restoration of nutrition & may be dwarf if undernutrition is profound.• Diagnosis: good dietary history, anthropometric measurements
  22. 22. Chronic Systemic Illness:1) Chronic Infections -eg:TB, Malaria, Leishmaniasis, Chr. pyelonephiritis - Growth retardation is due to impaired appetite, decreased food intake, increased catabolism, poor utilization of food, vomiting & diarrhoea2) Malabsorbtion Syndromes - eg: chronic recurrent infective diarrhoea, lactose intolerance, cystic fibrosis, celiac disease, giardiasis, cow’s milk allergy, abeta lipoproteinemiaIBD&COELIAC DISEASE- manifest with growth delay even before onset of GI symptoms.
  23. 23. 3) Birth defects: CHD, urinary tract & nervous system anomalies 4) Miscellaneous:(EVIDENCED CLINICALLY) Cirrhosis of liver, bronchiectasis, acquired heart diseases, cardiomyopathies, SDHRTA& Nephrogenic DI- may present from birth with FTT.
  24. 24. 2) Laron’s Syndrome - Metabolic disorder, AR inheritence - Clinically resembles hGH deficiency, but blood hGH levels are high - Somatomedin levels are low3) Type 1 Diabetes Mellitus - significant growth retardation - insulin has chondrotropic effect
  25. 25. 4) Hypothyroidism - Short, stocky child; dull looking, puffy face - Thickened skin & sct giving myxomatous appearance, cold intolerance - Protuberant abdomen with umbilical hernia - Infantile sexual development & delayed puberty - Bone age markedly delayed Diagnosis- Low T4 levels, high TSH levels
  26. 26. 5) Cushing syndrome: Growth retardation ( early feature)• Other features: Obesity, plethoric moon facies, abdominal striae , hypertension, decreased glucose tolerance 6) Gonadal disorders: - Adiposo genital dystrophy ( Frohlich syndrome) moderate growth retardation, bone age normal or slightly delayed - Precocious puberty: early fusion of epiphyseal centres
  27. 27. Psychosocial short stature:• 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
  28. 28. Skeletal dysplasias:• 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
  29. 29. Diagnosis• Detailed history• Careful examination• Laboratory evaluation
  30. 30. The child is short and short for the family – what next?• Is the child very much below the 3rd 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 3rd percentile and target range - investigate
  31. 31. 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
  32. 32. Clues to etiology from historyHistory EtiologyHistory of delay of puberty in parents Constitutional delay of growthLow Birth Weight SGANeonatal hypoglycemia, jaundice, micropenis GH deficiencyDietary intake Under nutritionHeadache, vomiting, visual problem Pituitary/ hypothalamic SOLLethargy, constipation, weight gain HypothyroidismPolyuria CRF, RTASocial history Psychosocial dwarfismDiarrhea, greasy stools Malabsorption
  33. 33. Pointers to etiology of short staturePointer EtiologyMidline defects, micropenis, Frontal bossing, GH deficiencydepressed nasal bridge, crowded teeth,Rickets Renal failure, RTA, malabsorptionPallor Renal failure, malabsorption, nutritional anemiaMalnutrition PEM, malabsorption, celiac disease, cystic fibrosisObesity Hypothyroidism, Cushing syndrome, Prader Willi syndromeMetacarpal shortening Turner syndrome, pseudohypoparathyroidismCardiac murmur Congenital heart disease, Turner syndromeMental retardation Hypothyroidism, Down/ Turner syndrome, pseudohypoparathyroidism
  34. 34. 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
  35. 35. Clues to etiology from examinationExamination finding EtiologyDisproportion Skeletal dysplasia, rickets, hypothyroidismDysmorphism Congenital syndromesInfantile appearance, micropenis Ghd, MphdHypertension CRFShort metacarpals Parathyroid dis, Turners, SXOX gene defectGoitre, coarse skin HypothyroidismCentral obesity, striae Cushing syndrome
  36. 36. Assessment of a child with short stature 1) Accurate height measurement• Below 2 yrs- supine length with infantometer.• For older children- harpenden Stadiometer
  37. 37. Height meaurement• Infanto meter:Child should be relaxedHead should be placed against an inflexible board.Legs fully extendedFeet placed perpendicular onto movable flat board.
  38. 38. 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
  39. 39. • SITTING HEIGHT:• It is the CRL in <2yrs of age• Measured upto ischial tuberosity.• Using sitting height stadiometer.• At birth:70%• At 3yrs: 57%• Adults:50%• SUB ISCHIAL LEG LENGTH:• Height-sitting height.• USEFUL IN MEASURING THE upper to lower body praportions.
  40. 40. 2) Assessment of body proportionUpper segment: Lower segment ratioIncrease: rickets, achondroplasia,untreated hypothyroidismDecrease: spondyloepiphyseal dysplasia, vertebral anomaliesComparison of arm span with height
  41. 41. 3) Comparison with child’s own genetic potential Mid parental height for boys = mothers height + fathers height /2 + 6.5cm Mid parental height for girls = mothers height + fathers height /2 – 6.5cm• usually the projected height is +/- 8cm or 2 S.D.4) Sexual maturity rating ( SMR):• Also known as Tanners stages• Used in older children• Total 5 stages included in each gender
  42. 42. Always Perform Sexual Maturity Rating
  43. 43. GENITALS IN MALESTAGE TESTI VOL PENILE SCROTUM AGE LENGTH1 <1.5ML ≤ 3CM - ≤ 9 YRS2 1.6-6 ML ≤ 3CM THIN RED 9-12 YRS ENLARGED3 6-12 ML 6 CM ENLARGES 11-12.5 YRS FURTHER4 12-20 ML 10CM ENLARGE DARK 12.5-14 YRS5 >20 ML 15 CM ADULT 14+
  44. 44. Males: SMR Pubic Hair• Stage 1 Preadolescent• Stage 2 Scanty, long, slightly pigmented, primarily at base of penis• Stage 3 Darker, coarser, starts to curl, small amount• Stage 4 Coarse, curly; resembles adult type but covers smaller area• Stage 5 Adult quantity and distribution, spread to medial thighs surface of thighs
  45. 45. 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.
  46. 46. SMR Breasts• Stage 1 Preadolescent; elevation of papilla only• Stage 2 Breast and papilla elevated as small mound; areola diameter increased• Stage 3 Breast and areola enlarged with no separation of their contours• Stage 4 Projection of areola and papilla to form secondary mound above the level of the breast• Stage 5 Mature; projection of papilla only, areola has recessed to the general contour of the breast
  47. 47. Investigation: 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 .
  48. 48. • 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
  49. 49. BONE AGE ( BA ):• 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
  50. 50. 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
  51. 51. Methods of bone age assessment• Tanner White House•• Greulich and Pyle• No of carpals – 2
  52. 52. G & P Method Patient’s film iscompared with thestandard of thesame sex andnearest age It is nextcompared withadjacent standard,both older andyounger to get theclosest match
  53. 53. Bone ageBetter correlate with SMRPredictor of future height
  54. 54. TW Method - 13 Bones
  55. 55. • 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
  56. 56. Delayed bone age• Constitutional short stature• Hypothyroidism• Celiac disease• GH deficiency
  57. 57. 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)
  58. 58. 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
  59. 59. 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
  60. 60. Growth hormone actions Growth Hormone GH receptors LiverMetabolic effectsMetabolic effects (Anabolic) Synthesis of IGF1 GH receptors IGF receptors Proliferation of Cells Linear Growth Linear growth Cellular growth
  61. 61. GROWTH HORMONE DEFICIENCY(GHD)• CONGENITAL: • ACQUIRED-Perinatal asphyxia, -idiopathic-CNS malformations -tumors(septo optic dysplasia) ( craniopharyngioma, glioma, germinoma) -trauma/surgery -cns infection/irradiation
  62. 62. Growth hormone deficiency - 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
  63. 63. 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
  64. 64. 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. <10ng/ml in response to 2 GH stim .test or<18ng/ml in response to combined Arg- GHRH stim test.
  65. 65. 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
  66. 66. 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)
  67. 67. growth hormone therapy• Currently approved as per FDA IN:• GHD• TURNERS SYNDROME• RENAL INSUFFIENCY• PRADER WILLE SYNDROME• NORMAL CHILDREN WITH HEIGHT <2.4 SD• SGA who have not reached 5th centile by 2yrs.• Shox (short stature homeobox gene)deficiency.
  68. 68. GH THERAPYDOSE: 0.1U/KG/DAY s.c. at night timeFollow up & watch for atleat one year before starting the treatment.Earlier is always better&ideal is 3-4yrsNever delay beyond 7-8yrsUsually growth velocity is maximum in first year of therapy. Devices: Freeze dried – commonest Liquid prep- easy to administer
  69. 69. Automated pen type
  70. 70. G H THERAPY Routes of administration:• S.c- currently using• Intranasal- under trials• Timing: 2-3 times/wk Response to Rx:• Max response in 1st year with growth velocity >95th percentile• With each increasing year the growth rate tends to decline.• If falls <25th percentile: assess compliance before increasing dose.
  71. 71. • 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 <1 inch/yearBA >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,
  72. 72. HYPOTHYROIDISM• CONGENITAL • ACQUIRED(UNTREATED) (UNTREATED): Slow growth vel.  Asymptomatic Delayd BA  Delayed growth Constipation  Constipation Mentally delayd unless  Normal IQif developed treated at 2-3 mnths. >2yrs of age  Dry skin
  73. 73. • Regardless of symptoms all children with significant short stature should be screened for hypothyroidism.• Rx: thyroxine usually started at 100 micro grams to be started.
  74. 74. 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
  75. 75.  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.
  76. 76. management• 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)
  77. 77. Thank You !!
  78. 78. Genghis Khan Voltaire Pablo Picasso

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