Short stature

!' - Looks up to look down upon ?How tall are you? Instead of.. What is your height

Height has been linked to:

Occupational successAchievement as an academicLeadership in armyHeroes are always big and high

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8000 7 " 1940 "

19 , Growth is a mirror of the conditions of society

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20 Secular changes in height in china during the 19th century

BoysGirlsZhen-Wang et al, annals of human biology, 2005

- 2SDS 2SDS - 3SDS Widleg-

AnthropometryHeight

WeightUS/LS ASHC

Physiology of growth

ALS

Multiple Functions of Growth Hormone

Familial short stature, constitutional Delay of Growth and puberty CF, , , Celiac, IBD Skeletal Dysplasia Hypothyroidism, Cushing, GH deficiciency, GHIS ISSFamilial/ Genetic short stature

Constitutional Delay of Growth and Puberty

Short stature- Celiac disease

Bhadada et al, J Gasr Nutr, 2006

Bhadada et al, J Gasr Nutr, 2006Case presentation15 y old girl referred for short stature Normal pregnancy, normal birth BW 2700 gRecurrent OM in childhoodDecreased hearing in the right earMenarche 12.5 y, regular menses every 28 d/ 5 H= 139 GV < 2cm/yBA 15y

Syndromic short stature- Turner syndrome

Physiology of growth

ALSIsolated GH defMPHDGHISGH DeficiencyPrimaryDefects in the development of the hypophysisSepto optic dysplasia, Defects in transcription factorsGenetic defects in GH synthesisGH gene mutationsSecondarySOL, Irradiation,trauma GH insensitivity defects in the GH receptor defects in intracellular signaling

Pituitary Transcription Factors

Specific clinical signs of GH deficiencyIn the neonate: hypoglycemia, prolonged jaundice, microphallus, traumatic deliveryConsangunity/ another family member affectedCranio facial midline anomaliesCranial irradiationHead traumaCNS infectionSevere short stature -3SDSHeigh < -2 SDS and hight velocity < -1SD over 1 yGrowth hormone deficiencyShort Stature Decreased growth rateHypoglycemiaMicropenisNormal proportionsOverweight for height

2626Growth hormone deficiency

Infantile cherubic faciesProminent foreheadSaddle noseDelayed teeth eruption (and delayed bone age)2727What GHD Looks Like

GHD subject is 18 cm shorter than her sister, despite being one and a half years older

28ISS- Idiopathic short statureDefinition: HSDS -2 or -2.25 GH sufficientNo relation to : familial target heightIGF-1, IGFBP3 levelsControversial issueA medical disorder?? A normal variant?? Approach to a child with short statureHistory: headache, abdominal pain, constipation, diarrhea, nocturiaPhysical examination: height, weight, Body proportions ( US/LS ratio, AS ), goiter, abdomen, dysmorphic features, pubertal stage history of parental pubertyGrowth velocity in 3-6 monthsLaboratory workup: CBC, ESR, urea, creatinine, urine culture and PH, stool for parasites, TTG, FT4, TSH, IGF1, IGFBP3, bone ageIf GV low or IGF1 IGFBP3 lowGH stimulation test:ArginineL-dopaGlucagonInsulinCriteria in Israel: 2 tests with secretion < 7.5 ug/ml

31If GH deficiency provedDo an MRI

GH- History30 years agoPituitary extract1985- CJD1985- first recombinant GH1987- second recombinant GHUnlimited GH supply

3434Indications improved in Israel for GH therapyMPHDIsolated GH deficiencySGATurner syndromePrader Willi SyndromeChronic renal failureISS

Turners Syndrome: Height before and after 7 yrs of GH Rx

3636Long-term responses to GH in Turners syndrome. Individual heights at start of study (open circles) and after seven years of GH Rx (red circles). Reference growth curves for healthy Dutch girls (solid lines) and untreated Turners girls (dotted lines).Effect of GH treatment on CRF

Side EffectsIntracranial hypertensionTonsillar hypertrophy?Slipped capital femoral epiphysisGlucose intolerance?Increased risk of cancer?

Mecasermin: Recombinant-human Insulin-like Growth Factor-1FDA-approved for long-term treatment for growth failure in children with severe primary IGF-1 deficiency or GH gene deletions who have developed neutralizing antibodiesPatients undergoing at least one year of mecasermin treatment demonstrated statistically significant improvements in growth Increlex Prescribing Information (Mecasermin, Tercica, N=71).

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